Objective: To assess the feasibility and accuracy of Cerenkov Luminescence Imaging (CLI) for assessment of surgical margins intraoperatively during radical prostatectomy (RPE). Methods: A single centre feasibility study included 10 patients with high-risk primary prostate cancer (PC). ⁶⁸Ga-PSMA PET/CT scans were performed followed by RPE and intraoperative CLI of the excised prostate. In addition to imaging the intact prostate, in the first two patients the prostate gland was incised and imaged with CLI to visualise the primary tumour. We compared the tumour margin status on CLI to postoperative histopathology. Measured CLI intensities were determined as tumour to background ratio (TBR). Results: Tumour cells were successfully detected on the incised prostate CLI images as confirmed by histopathology. 3 of 10 men had histopathological positive surgical margins (PSMs), and 2 of 3 PSMs were accurately detected on CLI. Overall, 25 (72%) out of 35 regions of interest (ROIs) proved to visualize a tumour signal according to standard histopathology. The median tumour radiance in these areas was 11301 photons/s/cm²/sr (range 3328 - 25428 photons/s/cm²/sr) and median TBR was 4.2 (range 2.1 – 11.6). False positive signals were seen mainly at the prostate base with PC cells overlaid by benign tissue. PSMA-immunohistochemistry (PSMA-IHC) revealed strong PSMA staining of benign gland tissue, which impacts measured activities. Conclusion: This feasibility showed that ⁶⁸Ga-PSMA CLI is a new intraoperative imaging technique capable of imaging the entire specimen’s surface to detect PC tissue at the resection margin. Further optimisation of the CLI protocol, or the use of lower-energetic imaging tracers such as ¹⁸F-PSMA, are required to reduce false positives. A larger study will be performed to assess diagnostic performance.

The aim of this work was to quantify the uptake of [¹⁸F]BMS-986192, a PD-L1 adnectin PET tracer, in patients with non-small-cell lung cancer (NSCLC). To this end, plasma input kinetic modeling of dynamic tumor uptake data with online arterial blood sampling was performed. In addition, the accuracy of simplified uptake metrics such as standardized uptake value (SUV) was investigated. Methods: Data from a study with [¹⁸F]BMS-986192 in patients with advanced stage NSCLC eligible for nivolumab treatment were used if a dynamic scan was available and lesions were present in the field of view of the dynamic scan. After injection of [¹⁸F]BMS-986192, a 60-minutes dynamic PET-CT scan was started, followed by a 30-min whole body PET-CT scan. Continuous arterial and discrete arterial and venous blood sampling were performed to determine a plasma input function. Tumor time activity curves were fitted by several plasma input kinetic models. Simplified uptake parameters included tumor to blood ratio as well as several SUV measures. Results: Twenty two tumors in nine patients were analyzed. The arterial plasma input single-tissue reversible compartment model with fitted blood volume fraction seems to be the most preferred model as it best fitted 11 out of 18 tumor time activity curves. The distribution volume V_T ranged from 0.4 to 4.8 mL·cm-3. Similar values were obtained with an image derived input function. From the simplified measures, SUV normalized for body weight (SUV_BW) at 50 and 67 minutes post injection correlated best with V_T, with an R² > 0.9. Conclusion: A single tissue reversible model can be used for the quantification of tumor uptake of the PD-L1 PET tracer [¹⁸F]BMS-986192. SUV_BW at 60 minutes post injection, normalized for body weight, is an accurate simplified parameter for uptake assessment of baseline studies. In order to assess its predictive value for response evaluation during PD-(L)1 immune checkpoint inhibition further validation of SUV against V_T based on an image derived input function is recommended.

The overexpression of integrin αvβ6 in pancreatic cancer makes it a promising target for noninvasive positron emission tomography (PET) imaging. However, currently, most integrin αvβ6-targeting radiotracers are based on linear peptides, which are quickly degraded in the serum by proteinases. Herein, we aimed to develop and assess a ⁶⁸Ga-labeled integrin αvβ6-targeting cyclic peptide (⁶⁸Ga-cycratide) for PET imaging of pancreatic cancer. Methods: ⁶⁸Ga-cycratide was prepared, and its PET imaging profile was compared with that of the linear peptide (⁶⁸Ga-linear-pep) in an integrin αvβ6-positive BxPC-3 human pancreatic cancer mouse model. Five healthy volunteers (two women and three men) underwent whole-body PET/CT imaging after injection of ⁶⁸Ga-cycratide, and biodistribution and dosimetry calculations were determined. PET/CT imaging of two patients was performed to investigate the potential role of ⁶⁸Ga-cycratide in pancreatic cancer diagnosis and treatment monitoring. Results: ⁶⁸Ga-cycratide exhibited significantly higher tumor uptake than did ⁶⁸Ga-linear-pep in BxPC-3 tumor-bearing mice, owing—at least in part—to markedly improved in vivo stability. ⁶⁸Ga-cycratide could sensitively detect the pancreatic cancer lesions in an orthotopic mouse model and was well tolerated in all healthy volunteers. Preliminary PET/CT imaging in patients with pancreatic cancer demonstrated that ⁶⁸Ga-cycratide was comparable to ¹⁸F-fludeoxyglucose for diagnostic imaging and post-surgery tumor relapse monitoring. Conclusion: ⁶⁸Ga-cycratide is an integrin αvβ6-specific PET radiotracer with favorable pharmacokinetics and dosimetry profile. ⁶⁸Ga-cycratide is expected to provide an effective noninvasive PET strategy for pancreatic cancer lesion detection and therapy response monitoring.

Background: Prostate-specific antigen (PSA) is widely used to monitor treatment response in patients with metastatic castration-resistant prostate cancer (mCRPC). However, PSA measurements are considered only after 12 wk of treatment. We aimed to evaluate the prognostic value of early PSA changes following ¹⁷⁷Lu-labelled prostate specific membrane antigen (LuPSMA) radionuclide treatment in mCRPC patients. Methods: Men who were treated under a compassionate access program with LuPSMA at our institution and had available PSA values at baseline, at 6 wk after treatment initiation were included in this retrospective analysis. Patients were assigned to three groups based on PSA changes: 1) response: ≥30% decline, 2) progression: ≥25% increase and 3) stable: <30% decline and <25% increase. The co-primary endpoints were overall survival and imaging-based progression-free survival. The secondary end points were PSA changes at 12 wk and PSA flare-up. Results: We identified 124 eligible patients with PSA values at 6 wk. A ≥30% decline in PSA at 6 wk was associated with longer overall survival (median 16.7 mo; 95%CI 14.4–19.0) compared with patients with stable PSA (median: 11.8 mo; 95%CI 8.6–15.1; P = 0.007) and progression (median: 6.5 mo; 95%CI 5.2–7.8; p<0.001). Patients with ≥30% decline in PSA at 6 wk also had a reduced risk of imaging-based progression compared with patients with stable PSA (HR: 0.60; 95%CI 0.38–0.94; P = 0.02), while patients with PSA progression had a higher risk of imaging-based progression compared with those showing stable PSA (HR: 3.18; 95%CI 1.95–5.21; p<0.001). The percentage changes of PSA at 6 wk and 12 wk were highly associated (r=0.90; p<0.001). 29 of 31 (94%) patients who experienced early PSA progression at 6 wk achieved biochemical progression at 12 wk. Overall, only 1 of 36 (3%) patients with PSA progression at 6 wk achieved any PSA decline at 12 wk (1% of the entire cohort). Limitations of the study included its retrospective nature and the single center experience. Conclusion: PSA changes at 6 wk after LuPSMA initiation are an early indicator of long-term clinical outcome. Patients progressing by PSA after 6 wk of treatment could benefit from a very early treatment switch decision. PSA flare-up during LuPSMA treatment is very uncommon. Prospective studies are now warranted to validate our findings and potentially inform clinicians earlier on the effectiveness of LuPSMA.

Purpose: This prospective study evaluated the imaging performance of a novel immunological pretargeting positron-emission tomorgraphy (immuno-PET) method in patients with HER2-negative, carcinoembryonic antigen (CEA)-positive, metastatic breast cancer (BC), compared to computed tomography (CT), bone magnetic resonance imaging (MRI), and ¹⁸Fluorodeoxyglucose PET (FDG-PET). Patients and Methods: Twenty-three patients underwent whole-body immuno-PET after injection of 150 MBq ⁶⁸Ga-IMP288, a histamine-succinyl-glycine peptide given following initial targeting of a trivalent anti-CEA, bispecific, anti-peptide antibody. The gold standards were histology and imaging follow-up. Tumor standard uptake values (SUV_max and SUVmean) were measured, and tumor burden analyzed using Total Tumor Volume (TTV) and Total Lesion Activity (TLA). Results: Total lesion sensitivity of immuno-PET and FDG-PET was 94.7% (1116/1178) and 89.6% (1056/1178), respectively. Immuno-PET had a somewhat higher sensitivity than CT and FDG-PET in lymph nodes (92.4% vs 69.7% and 89.4%, respectively) and liver metastases (97.3% vs 92.1% and 94.8%, respectively), whereas sensitivity was lower for lung metastases (48.3% vs 100% and 75.9%, respectively). Immuno-PET showed higher sensitivity than MRI and FDG-PET for bone lesions (95.8% vs 90.7% and 89.3%, respectively). In contrast to FDG-PET, immuno-PET disclosed brain metastases. Despite equivalent tumor SUV_max, SUVmean, and TTV, TLA was significantly higher with immuno-PET compared to FDG PET (P = 0.009). Conclusion: Immuno-PET using anti-CEA/anti-IMP288 bispecific antibody, followed by ⁶⁸Ga-IMP288, is a potentially sensitive theranostic imaging method for HER2-negative, CEA-positive, metastatic BC patients, and warrants further research.

For individual treatment decisions in patients with metastatic prostate cancer (mPC), molecular diagnostics are increasingly used. Bone metastases are frequently the only source for obtaining metastatic tumor tissue. However, the success rate of computed tomography (CT)-guided bone biopsies for molecular analyses in mPC patients is only ~40%. Positron emission tomography (PET) using Gallium-68 prostate specific membrane antigen (⁶⁸Ga-PSMA) is a promising tool to improve the harvest rate of bone biopsies for molecular analyses. Aim of this study was to determine the success rate of ⁶⁸Ga-PSMA guided bone biopsies for molecular diagnostics in mPC patients. Methods: Within a prospective multicenter whole-genome sequencing trial (NCT01855477), 69 mPC patients underwent ⁶⁸Ga-PSMA PET/CT prior to bone biopsy. Primary endpoint was success rate (tumor percentage ≥30%) of ⁶⁸Ga-PSMA guided bone biopsies. At biopsy sites, ⁶⁸Ga-PSMA uptake was quantified using rigid body image registration of ⁶⁸Ga-PSMA PET/CT and interventional CT. Actionable somatic alterations were identified. Results: Success rate of ⁶⁸Ga-PSMA guided biopsies for molecular analyses was 70%. At biopsy sites categorized as positive, inconclusive, or negative for ⁶⁸Ga-PSMA uptake, 70%, 64%, and 36% of biopsies were tumor positive (≥30%), respectively (P = 0.0610). In tumor positive biopsies, ⁶⁸Ga-PSMA uptake was significantly higher (P = 0.008), whereas radiodensity was significantly lower (P = 0.006). With an area under the curve of 0.84 and 0.70, both ⁶⁸Ga-PSMA uptake (maximum standardized uptake value) and radiodensity (mean Hounsfield Units) were strong predictors for a positive biopsy. Actionable somatic alterations were detected in 73% of the sequenced biopsies. Conclusion: In patients with mPC, ⁶⁸Ga-PSMA PET/CT improves the success rate of CT-guided bone biopsies for molecular analyses, thereby identifying actionable somatic alterations in more patients. Therefore, ⁶⁸Ga-PSMA PET/CT may be considered for guidance of bone biopsies in both clinical practice and clinical trials.

Introduction: Neuroendocrine differentiation is associated with treatment failure and poor outcome in metastatic castration-resistant prostate cancer (mCRPC). We investigated the effect of circulating neuroendocrine biomarkers on the efficacy of PSMA-targeted radioligand therapy (RLT). Methods: Neuroendocrine biomarker profiles (progastrin-releasing peptide, neuron-specific enolase, and chromogranin-A) were analyzed in 50 patients commencing ¹⁷⁷Lu-PSMA-617 RLT. The primary endpoint was PSA response in relation to baseline neuroendocrine marker profiles. Additional endpoints included progression-free survival. Tumor uptake on post-therapeutic scans, a known predictive marker for response, was used as control-variable. Results: Neuroendocrine biomarker profiles were abnormal in the majority of patients. Neuroendocrine biomarker levels did not predict treatment failure or early progression (P ≥ 0.13). By contrast, intense PSMA-ligand uptake in metastases predicted both treatment response (P = 0.0030) and reduced risk of early progression (P = 0.0111). Conclusion: Neuroendocrine marker profiles do not predict adverse outcome of RLT. By contrast, high ligand uptake was confirmed to be crucial for achieving tumor-response.

para-Aminobenzoic acid (PABA) has been previously used as an exogenous marker to verify completion of 24-hour urine sampling. Therefore, we hypothesized that radiolabeled PABA with ¹¹C could allow high-quality dynamic PET of the kidneys while reducing the radiation exposure due to its short biological and physical half-lives. We evaluated if ¹¹C-PABA could visualize renal anatomy and quantify function in healthy rats, rabbits, and first-in-human studies in healthy volunteers. Methods: Healthy rats and rabbits were injected with ¹¹C-PABA intravenously. Subsequently, a dynamic PET was performed, followed by post-mortem tissue biodistribution studies. 11C-PABA PET was directly compared with the current standard, ^99mTc-MAG3 in rats. Three healthy human subjects also underwent dynamic PET after intravenous injection of ¹¹C-PABA. Results: In healthy rats and rabbits, dynamic PET demonstrated a rapid accumulation of ¹¹C-PABA in the renal cortex, followed by rapid excretion through the pelvicalyceal system. In humans, ¹¹C-PABA PET was safe and well tolerated. There were no adverse or clinically detectable pharmacologic effects in any subject. The cortex was delineated on PET, and the activity gradually transited to the medulla and then renal pelvis with high spatiotemporal resolution. Conclusion: ¹¹C-PABA demonstrated fast renal excretion with very low background signal in animals and humans. These results suggest that ¹¹C-PABA could be used as a novel radiotracer for functional renal imaging, providing high-quality spatiotemporal images with low radiation exposure.

Purpose: To determine the effect of smooth filter and partial volume correction (PVC) method on measured prostate-specific membrane antigen (PSMA) activity in small metastatic lesions and to determine the impact of these changes on the molecular imaging (mi) PSMA scoring. Materials & Methods: Men with biochemical recurrence of prostate cancer with negative CT and bone scintigraphy were referred for ¹⁸F-DCFPyL PET/CT. Examinations were performed on one of 2 PET/CT scanners (GE Discovery 610 or Siemens mCT40). All suspected tumor sites were manually contoured on co-registered CT and PET images, and each was assigned a miPSMA score as per the PROMISE criteria. The PVC factors were calculated for every lesion using the anatomical CT and then applied to the unsmoothed PET images. The miPSMA scores, with and without the corrections, were compared, and a simplified "rule of thumb" (RoT) correction factor (CF) was derived for lesions at various sizes (<4mm, 4-7mm, 7-9mm, 9-12mm). This was then applied to the original dataset and miPSMA scores obtained using the RoT CF were compared to those found using the actual corrections. Results: There were 75 men (median age, 69 years; median serum PSA of 3.69 ug/L) with 232 metastatic nodes < 12 mm in diameter (mean lesion volume of 313.5 ± 309.6 mm³). Mean SUV_max before and after correction was 11.0 ± 9.3 and 28.5 ± 22.8, respectively (p<0.00001). The mean CF for lesions <4mm (n = 22), 4-7mm (n = 140), 7-9mm (n = 50), 9-12 mm (n = 20) was 4 (range: 2.5-6.4), 2.8 (range: 1.6-4.9), 2.3 (range: 1.6-3.3) and 1.8 (range 1.4-2.4), respectively. Overall miPSMA scores were concordant between the corrected dataset and RoT in 205/232 lesions (88.4%). Conclusion: There is a significant effect of smooth filter and partial volume correction on measured PSMA activity in small nodal metastases, impacting the miPSMA score.

A data-driven method for respiratory gating in PET has recently been commercially developed. We sought to compare the performance of the algorithm to an external, device-based system for oncological [¹⁸F]-FDG PET/CT imaging. Methods: 144 whole-body [¹⁸F]-FDG PET/CT examinations were acquired using a Discovery D690 or D710 PET/CT scanner (GE Healthcare), with a respiratory gating waveform recorded by an external, device based respiratory gating system. In each examination, two of the bed positions covering the liver and lung bases were acquired with duration of 6 minutes. Quiescent period gating retaining ~50% of coincidences was then able to produce images with an effective duration of 3 minutes for these two bed positions, matching the other bed positions. For each exam, 4 reconstructions were performed and compared: data driven gating (DDG-retro), external device-based gating (RPM Gated), no gating but using only the first 3 minutes of data (Ungated Matched), and no gating retaining all coincidences (Ungated Full). Lesions in the images were quantified and image quality was scored by a radiologist, blinded to the method of data processing. Results: The use of DDG-retro was found to increase SUVmax and to decrease the threshold-defined lesion volume in comparison to each of the other reconstruction options. Compared to RPM-gated, DDG-retro gave an average increase in SUV_max of 0.66 ± 0.1 g/mL (n=87, p<0.0005). Although results from the blinded image evaluation were most commonly equivalent, DDG-retro was preferred over RPM gated in 13% of exams while the opposite occurred in just 2% of exams. This was a significant preference for DDG-retro (p=0.008, n=121). Liver lesions were identified in 23 exams. Considering this subset of data, DDG-retro was ranked superior to Ungated Full in 6/23 (26%) of cases. Gated reconstruction using the external device failed in 16% of exams, while DDG-retro always provided a clinically acceptable image. Conclusion: In this clinical evaluation, the data driven respiratory gating technique provided superior performance as compared to the external device-based system. For the majority of exams the performance was equivalent, but data driven respiratory gating had superior performance in 13% of exams, leading to a significant preference overall.

Rationale: Currently available imaging techniques have limited specificity for the detection of active myocardial inflammation. Aluminum fluoride-18-labeled 1,4,7-triazacyclononane-N,N',N''-triacetic acid conjugated folate (¹⁸F-FOL) is a positron emission tomography (PET) tracer targeting folate receptor β (FR-β) that is expressed on activated macrophages at sites of inflammation. We evaluated ¹⁸F-FOL PET for the detection of myocardial inflammation in rats with autoimmune myocarditis and studied expression of FR-β in human cardiac sarcoidosis specimens. Methods: Myocarditis was induced by immunizing rats (n = 18) with porcine cardiac myosin in complete Freund’s adjuvant. Control rats (n = 6) were injected with Freund’s adjuvant alone. ¹⁸F-FOL was intravenously injected followed by imaging with a small animal PET/computed tomography (CT) scanner and autoradiography. Contrast-enhanced high-resolution CT or 2-deoxy-2-¹⁸F-fluoro-D-glucose (¹⁸F-FDG) PET images were used for co-registration. Rat tissue sections and myocardial autopsy samples of 6 patients with cardiac sarcoidosis were studied for macrophages and FR-β. Results: The myocardium of 10 out of 18 immunized rats showed focal macrophage-rich inflammatory lesions with FR-β expression occurring mainly in M1-polarized macrophages. PET images showed focal myocardial ¹⁸F-FOL uptake co-localizing with inflammatory lesions (SUVmean, 2.1 ± 1.1), whereas uptake in the remote myocardium of immunized rats and controls was low (SUVmean, 0.4 ± 0.2 and 0.4 ± 0.1, respectively; P < 0.01). Ex vivo autoradiography of tissue sections confirmed uptake of ¹⁸F-FOL in myocardial inflammatory lesions. Uptake of ¹⁸F-FOL to inflamed myocardium was efficiently blocked by a non-labeled FR-β ligand folate glucosamine in vivo. The myocardium of patients with cardiac sarcoidosis showed many FR-β-positive macrophages in inflammatory lesions. Conclusion: In a rat model of autoimmune myocarditis, ¹⁸F-FOL shows specific uptake in inflamed myocardium containing macrophages expressing FR-β, which were also present in human cardiac sarcoid lesions. Imaging of FR-β expression is a potential approach for the detection of active myocardial inflammation.

BiTE® (Bispecific T-cell engager) molecules are designed to engage and activate cytotoxic T-cells to kill tumor cells. Little is known about their biodistribution in immunocompetent settings. To explore their pharmacokinetics and the role of the immune cells, BiTE molecules were radiolabeled with positron emission tomography (PET) isotope zirconium-89 (89Zr) and studied in immunocompetent and immunodeficient mouse models. PET images and ex-vivo biodistribution in immunocompetent mice with 89Zr-muS110, targeting mouse CD3 (Kd = 2.9 nM) and mouse EpCAM (Kd = 21 nM), and 89Zr-hyS110, targeting only mouse CD3 (Kd = 2.9 nM), showed uptake in tumor, spleen and other lymphoid organs, while the human-specific control BiTE 89Zr-AMG 110 showed similar tumor uptake but lacked spleen uptake. 89Zr-muS110 spleen uptake was lower in immunodeficient than in immunocompetent mice. After repeated administration of non-radiolabeled muS110 to immunocompetent mice 89Zr-muS110 uptake in spleen, and other lymphoid tissues, decreased and was comparable to uptake in immunodeficient mice, indicating saturation of CD3 binding sites. Autoradiography and immunohistochemistry demonstrated colocalization of 89Zr-muS110 and 89Zr-hyS110 with CD3-positive T-cells in the tumor and spleen but not with EpCAM expression. Also, uptake in the duodenum correlated with a high incidence of T-cells. This study shows that in immunocompetent mice the BiTE 89Zr-muS110 distribution is predominantly based on its high affinity CD3 binding arm. Significance: 89Zr-muS110 biodistribution is mainly dependent on the T-cell targeting arm with limited contribution of its second arm, targeting EpCAM. These findings highlight the need for extensive biodistribution studies of novel bispecific constructs as results might have implications for their respective drug development and clinical translation.

Gone are the days when medical imaging was used primarily to visualize anatomical structures. The emergence of molecular imaging, championed by radiolabeled fluorodeoxyglucose positron emission tomography (¹⁸FDG PET) has expanded the information content derived from imaging to include pathophysiological and molecular processes. Cancer imaging, in particular, has leveraged advances in molecular imaging agents and technology to improve the accuracy of tumor detection, interrogate tumor heterogeneity, monitor treatment response, focus surgical resection, and enable image-guided biopsy. Surgeons are actively latching on to the incredible opportunities provided by medical imaging for preoperative planning, intraoperative guidance, and postoperative monitoring. From label-free techniques to enabling cancer-selective imaging agents, image-guided surgery provides surgical oncologists and interventional radiologists both macroscopic and microscopic views of cancer in the operating room. This review highlights the current state of molecular imaging and sensing approaches available for surgical guidance. Salient features of nuclear, optical, and multimodal approaches will be discussed, including their strengths, limitations and clinical applications. To address the increasing complexity and diversity of methods available today, this review provides a framework to identify a contrast mechanism, suitable modality, and device. Emerging low cost, portable, and user-friendly imaging systems make the case for adopting some of these technologies as the global standard of care in surgical practice.

Radionuclide imaging of myocardial perfusion, function, and viability has been established for decades and remains a robust, evidence-based and broadly available means for clinical workup and therapeutic guidance in ischemic heart disease. Yet, powerful alternative modalities have emerged for this purpose, and their growth has resulted in increasing competition. But the potential of the tracer principle goes beyond the assessment of physiology and function, towards the interrogation of biology and molecular pathways. This is a unique selling point of radionuclide imaging, which has been under-recognized in cardiovascular medicine until recently. Now, molecular imaging methods for the detection of myocardial infiltration, device infection and cardiovascular inflammation are successfully gaining clinical acceptance. This is further strengthened by the symbiotic quest of cardiac imaging and therapy for an increasing implementation of molecular-targeted procedures, where specific therapeutic interventions require specific diagnostic guidance towards the most suitable candidates. This review will summarize the current advent of clinical cardiovascular molecular imaging and highlight its transformative contribution to the evolution of cardiovascular therapy beyond mechanical interventions and broad "blockbuster" medication, towards a future of novel, individualized molecular targeted and molecular imaging-guided therapies.

Bone is the most common site of distant metastatic spread in prostate adenocarcinoma. Prostate-specific membrane antigen uptake has been described in both benign and malignant bone lesions, which can lead to false-positive findings on ⁶⁸Ga-prostate-specific membrane antigen-11 positron emission tomography (⁶⁸Ga-PSMA-11 PET). The purpose of this study was to evaluate the diagnostic accuracy of ⁶⁸Ga-PSMA-11 PET for osseous prostate cancer metastases and improve bone uptake interpretation using semi-quantitative metrics. METHODS: 56 prostate cancer patients (18 pre-prostatectomy, 38 biochemical recurrence) who underwent ⁶⁸Ga-PSMA-11 PET/MRI or PET/CT examinations with osseous PSMA-ligand uptake were included in the study. Medical records were reviewed retrospectively by board-certified nuclear radiologists to determine true or false positivity based on a composite endpoint. For each avid osseous lesion, biological volume, size, PSMA-RADS rating, maximum standardized uptake value (SUV_max), and ratio of lesion SUV_max to liver, blood pool, and background bone SUV_max were measured. Differences between benign and malignant lesions were evaluated for statistical significance, and cut-off values for these parameters were determined to maximize diagnostic accuracy. RESULTS: Among 56 participants, 13 patients (22.8%) had false-positive osseous ⁶⁸Ga-PSMA-11 findings and 43 patients (76.8%) had true-positive osseous ⁶⁸Ga-PSMA-11 findings. Twenty-two patients (39%) had 1 osseous lesion, 18 (32%) had 2-4 lesions, and 16 (29%) had 5 or more lesions. Cut-off values resulting in statistically significant (p<0.005) differences between benign and malignant lesions were: PSMA-RADS ≥4, SUV_max ≥4.1, SUV_max ratio of lesion to blood pool ≥2.11, to liver ≥0.55, and to bone ≥4.4. These measurements corresponded to lesion-based ⁶⁸Ga-PSMA-11 PET lesion detection rate for malignancy of 80%, 93%, 89%, 21%, 89%, and a specificity of 73%, 73%, 73%, 93%, 60%, respectively. CONCLUSION: PSMA-RADS rating, SUV_max, and SUV_max ratio of lesion to blood pool can help differentiate benign from malignant lesions on ⁶⁸Ga-PSMA-11 PET. SUV_max ratio to blood pool above 2.2 is a reasonable parameter to support image interpretation and presented superior lesion detection rate and specificity when compared to visual interpretation by PSMA RADS. These parameters hold clinical value by improving diagnostic accuracy for metastatic prostate cancer on ⁶⁸Ga-PSMA-11 PET/MRI and PET/CT.

Fibroblast activation protein (FAP) has emerged as an interesting molecular target used in the imaging and therapy of various types of cancers. Gallium-68–labeled chelator-linked FAP inhibitors (FAPIs) have been successfully applied to positron emission tomography (PET) imaging of various tumor types. To broaden the spectrum of applicable PET tracers for extended imaging studies of FAP-dependent diseases, we herein report the radiosynthesis and preclinical evaluation of an ¹⁸F–labeled glycosylated FAP inhibitor ([¹⁸F]FGlc-FAPI). Methods: An alkyne-bearing precursor was synthesized and subjected to click chemistry–based radiosynthesis of [¹⁸F]FGlc-FAPI by two-step ¹⁸F-fluoroglycosylation. FAP-expressing HT1080hFAP cells were used to study competitive binding to FAP, cellular uptake, internalization, and efflux of [¹⁸F]FGlc-FAPI in vitro. Biodistribution studies and in vivo small animal PET studies of [¹⁸F]FGlc-FAPI compared to [⁶⁸Ga]Ga-FAPI-04 were conducted in nude mice bearing HT1080hFAP tumors or U87MG xenografts. Results: [¹⁸F]FGlc-FAPI was synthesized with a 15% radioactivity yield and a high radiochemical purity of >99%. In HT1080hFAP cells, [¹⁸F]FGlc-FAPI showed specific uptake, a high internalized fraction, and low cellular efflux. Compared to FAPI-04 (IC50 = 32 nM), the glycoconjugate, FGlc-FAPI (IC50 = 167 nM), showed slightly lower affinity for FAP in vitro, while plasma protein binding was higher for [¹⁸F]FGlc-FAPI. Biodistribution studies revealed significant hepatobiliary excretion of [¹⁸F]FGlc-FAPI; however, small animal PET studies in HT1080hFAP xenografts showed higher specific tumor uptake of [¹⁸F]FGlc-FAPI (4.5 % injected dose per gram of tissue [ID/g]) compared to [⁶⁸Ga]Ga-FAPI-04 (2 %ID/g). In U87MG tumor–bearing mice, both tracers showed similar tumor uptake, but [¹⁸F]FGlc-FAPI showed a higher tumor retention. Interestingly, [¹⁸F]FGlc-FAPI demonstrated high specific uptake in bone structures and joints. Conclusion: [¹⁸F]FGlc-FAPI is an interesting candidate for translation to the clinic, taking advantage of the longer half-life and physical imaging properties of F-18. The availability of [¹⁸F]FGlc-FAPI may allow extended PET studies of FAP-related diseases, such as cancer, but also arthritis, heart diseases, or pulmonary fibrosis.

Prostate specific membrane antigen (PSMA) targeting Positron Emission Tomography (PET) imaging is becoming the reference standard for prostate cancer (PC) staging, especially in advanced disease. Yet, the implications of PSMA-PET derived whole-body tumor volume for overall survival are poorly elucidated to date. This might be due to the fact that (semi-) automated quantification of whole-body tumor volume as PSMA-PET biomarker is an unmet clinical challenge. Therefore, a novel semi-automated software is proposed and evaluated by the present study, which enables the semi-automated quantification of PSMA-PET biomarkers such as whole-body tumor volume. Methods: The proposed quantification is implemented as a research prototype (MI Whole Body Analysis Suite, v1.0, Siemens Medical Solutions USA, Inc., Knoxville, TN). PSMA accumulating foci were automatically segmented by a percental threshold (50% of local SUV_max). Neural networks were trained to segment organs in PET-CT acquisitions (training CTs: 8,632, validation CTs: 53). Thereby, PSMA foci within organs of physiologic PSMA uptake were semi-automatically excluded from the analysis. Pretherapeutic PSMA-PET-CTs of 40 consecutive patients treated with ¹⁷⁷Lu-PSMA-617 therapy were evaluated in this analysis. The volumetric whole-body tumor volume (PSMATV50), SUV_max, SUVmean and other whole-body imaging biomarkers were calculated for each patient. Semi-automatically derived results were compared with manual readings in a sub-cohort (by one nuclear medicine physician using syngo.MM Oncology software, Siemens Healthineers, Knoxville, TN). Additionally, an inter-observer evaluation of the semi-automated approach was performed in a sub-cohort (by two nuclear medicine physicians). Results: Manually and semi automatically derived PSMA metrics were highly correlated (PSMATV50: R2=1.000; p<0.001; SUV_max: R2=0.988; p<0.001). The inter-observer agreement of the semi-automated workflow was also high (PSMATV50: R2=1.000; p<0.001; ICC=1.000; SUV_max: R2=0.988; p<0.001; ICC=0.997). PSMATV50 [ml] was a significant predictor of overall survival (HR: 1.004; 95%CI: 1.001-1.006, P = 0.002) and remained so in a multivariate regression including other biomarkers (HR: 1.004; 95%CI: 1.001-1.006 P = 0.004). Conclusion: PSMATV50 is a promising PSMA-PET biomarker that is reproducible and easily quantified by the proposed semi-automated software. Moreover, PSMATV50 is a significant predictor of overall survival in patients with advanced prostate cancer that receive ¹⁷⁷Lu-PSMA-617 therapy.

Purpose: We aimed to conduct a systematic review and meta-analysis of studies reporting the performance of radioactive iodine therapy (131-I therapy) in differentiating thyroid cancer (DTC) patients requiring a completion treatment following lobectomy. We also evaluated the response to 131-I therapy according to 2015ATA guidelines and the adverse events. Methods: A specific search strategy was designed to find articles evaluating the use of I-131 in patients with evidence of DTC after lobectomy. PubMed, CENTRAL, Scopus and Web of Science were searched. The search was updated until January 2020, without language restriction. Data were cross-checked and any discrepancy discussed. A proportion meta-analysis (with 95%CI) was performed using the random-effects model. Meta-regressions on I-131 success were attempted. Results: The pooled success ablation rate was 69% with better results in patients receiving a single administration of about 3.7 GBq; high heterogeneity was found (I2 85%), and publication bias was absent (Egger test: P = 0.57). Incomplete structural responses were recorded in only 14 of 695 (2%) patients enrolled in our analysis. Incomplete biochemical responses were observed in 8 to 24% of patients, with higher rates (24%) in patients receiving low radioiodine activities (~1.1 GBq) and lower rates (from 8 to 18%) in patients receiving higher activities of radioiodine (~3.7 Gbq). Neck pain due to thyroiditis was reported in up to 18% of patients but, in most cases, symptoms resolved after oral paracetamol or a short course of prednisone. Conclusion: Lobar ablation with 131-I is effective especially when high ¹³¹I activities are used. However, the rate of incomplete biochemical response to initial treatment appears to be slightly higher than the classical scheme of initial treatment of DTC. "Radioisotopic lobectomy" should be considered for patients with low-to-intermediate risk DTC requiring completion treatment after lobectomy due to specific individual risk factors and/or patient’s preferences.

At diagnosis 22% of colorectal cancer (CRC) patients have metastases and 50% later develop metastasis. Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (¹⁷⁷Lu)-PSMA-617 is employed to treat metastatic prostate cancer (PC). ¹⁷⁷Lu-PSMA-617 targets Prostate Specific Membrane Antigen (PSMA) a cell surface protein enriched in PC and the neovasculature of other solid tumors including CRC. We performed gallium-68 (⁶⁸Ga)-PSMA-11 PET-CT imaging of ten metastatic CRC patients to assess metastasis avidity. Eight patients had lesions lacking avidity and two had solitary metastases exhibiting very low avidity. Despite expression of PSMA in CRC neovasculature, none of the patients exhibited tumor avidity sufficient to be considered for ¹⁷⁷Lu-PSMA-617 PRRT.

The purpose of this study was to establish the dose-response relationship of selective internal radiation therapy (SIRT) in patients with metastatic colorectal cancer (mCRC), when informed by radiobiological sensitivity parameters derived from mCRC cell lines exposed to yttrium-90 (⁹⁰Y). Methods: 23 mCRC patients with liver metastases refractory to chemotherapy were included. ⁹⁰Y bremsstrahlung SPECT images were transformed into dose maps assuming the local dose deposition method. Baseline and follow-up CT scans were segmented to derive liver and tumor volumes. Mean, median, and D₇₀ (minimum dose to 70% of tumor volume) values determined from dose maps were correlated with change in tumor volume and vRECIST response using linear and logistic regression, respectively. Radiosensitivity parameters determined by clonogenic assays of mCRC cell lines HT-29 and DLD-1 after exposure to ⁹⁰Y or external beam radiotherapy (EBRT; 6MV photons) were used in biological effective dose (BED) calculations. Results: Mean administered radioactivity was 1469±428 MBq (847-2185 MBq), achieving a mean radiation absorbed tumor dose of 35.5±9.4 Gy and mean normal liver dose of 26.4±6.8 Gy. A 1.0 Gy increase in mean, median, and D₇₀ absorbed dose was associated with reduction in tumor volume of 1.8%, 1.8%, and 1.5%, respectively, and increased probability of vRECIST response (odds ratio: 1.09, 1.09, and 1.10 respectively). Threshold mean, median and D₇₀ doses for response were 48.3, 48.8, and 41.8 Gy respectively. EBRT-equivalent BEDs for ⁹⁰Y are up to 50% smaller than those calculated by applying protraction-corrected radiobiological parameters derived from EBRT alone. Conclusion: Dosimetric studies have assumed equivalence between ⁹⁰Y SIRT and EBRT, leading to inflation of BED for SIRT and possible under-treatment. Radiobiological parameters for ⁹⁰Y were applied to a BED model, providing a calculation method that has the potential to improve assessment of tumor control.

Purpose: This study is designed to assess the safety and therapeutic response to ¹⁷⁷Lu-EB-PSMA treatment with escalating doses in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: With institutional review board approval and informed consent, patients were randomly divided into three groups: Group A (n = 10) were treated with 1.18 ± 0.09 GBq/dose of ¹⁷⁷Lu-EB-PSMA. Group B (n = 10) were treated with 2.12 ± 0.19 GBq/dose of ¹⁷⁷Lu-EB-PSMA. Group C (n = 8) were treated with 3.52 ± 0.58 GBq/dose of ¹⁷⁷Lu-EB-PSMA. Eligible patients received up to three cycles of ¹⁷⁷Lu-EB-PSMA therapy, at eight-week intervals. Results: Due to disease progression or bone marrow suppression, 4 out of 10, 5 out of 10, and 5 out of 10 patients completed three cycles therapy as planned in Groups A, B, and C, respectively. The prostate-specific antigen (PSA) response was correlated with treatment dose, with PSA disease control rates in Group B (70%) and C (75%) being higher than that in Group A (10%) (P = 0.007), but no correlation between Group B and Group C was found. ⁶⁸Ga-PSMA PET/CT showed response in all the treatment groups, however, there was no significant difference between the three groups. Hematologic toxicity study found that platelets in Group B and Group C decreased more than those in Group A, and that Grade 4 thrombocytopenia occurred in 2 (25.0%) patients in Group C. No serious nephritic or hepatic side effects were observed. Conclusion: This study demonstrates that 2.12 GBq/dose of ¹⁷⁷Lu-EB-PSMA seems to be safe and adequate in tumor treatment. Further investigations with increased number of patients are warranted.

In randomized clinical trials (RCTs), no survival benefit has been observed for selective internal radiotherapy (SIRT) over sorafenib in patients with advanced hepatocellular carcinoma (aHCC). This study aimed to assess by means of a meta-analysis whether overall survival (OS) with SIRT, as monotherapy or followed by sorafenib, is non-inferior to sorafenib, and compare safety profiles for patients with aHCC. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library up to February 2019 to identify RCTs comparing SIRT as monotherapy, or followed by sorafenib, to sorafenib monotherapy among patients with aHCC. The main outcomes were OS and frequency of treatment-related severe adverse events (AEs grade ≥3). The per-protocol population was the primary analysis population. A non-inferiority margin of 1.08 in terms of hazard ratio (HR) was pre-specified for the upper boundary of 95% confidence interval (CI) for OS. Pre-specified subgroup analyses were performed. Results: Three RCTs, involving 1,243 patients, comparing sorafenib with SIRT (SIRveNIB and SARAH) or SIRT followed by sorafenib (SORAMIC), were included. After randomization, 411/635 (64.7%) patients allocated to SIRT and 522/608 (85.8%) allocated to sorafenib completed the studies without major protocol deviations. Median OS with SIRT, whether or not followed by sorafenib, was non-inferior to sorafenib (10.2 and 9.2 months, [HR 0.91, 95% CI 0.78–1.05]). Treatment-related severe adverse events were reported in 149/515 patients (28.9%) who received SIRT and 249/575 (43.3%) who received sorafenib only (p<0.01). Conclusion: SIRT as initial therapy for aHCC is non-inferior to sorafenib in terms of OS, and offers a better safety profile.

Introduction: Prostate-specific membrane antigen ligand positron emission tomography (PSMA PET) induces management changes in patients with prostate cancer. We aim to better characterize the impact of PSMA PET on management of recurrent prostate cancer in a large prospective cohort. Methods: We report management changes following PSMA PET, a secondary endpoint of a prospective multicenter trial in men with prostate cancer biochemical recurrence. Pre-PET (Q1), Post-PET (Q2) and Post-Treatment (Q3) questionnaires were sent to referring physicians recording site of recurrence, intended (Q1 to Q2 change) and implemented (Q3) therapeutic and diagnostic management. Results: Q1/Q2 response was collected for 382/635 (60%, intended cohort), Q1/Q2/Q3 for 206 patients (32%, implemented cohort). Intended management change (Q1/2) occurred in 260/382 (68%) patients. Intended change (Q1/2) was considered major in 176/382 (46%) patients. Major changes occurred most often for patients with PSA of 0.5 to <2.0 ng/mL (81/147, 55%). By analysis of stage-groups, management change was consistent with PET disease location, i.e. majority of major changes towards active surveillance (47%) for unknown disease site (103/382, 27%), towards local/focal therapy (56%) for locoregional disease (126/382, 33%), and towards systemic therapy (69% M1a; 43% M1b/c) for metastatic disease (153/382, 40%). According to Q3 responses, intended management was implemented in 160/206 (78%) patients. A total of 150 intended diagnostic tests, mostly CT (n = 43, 29%) and bone Scans/NaF-PET (n = 52, 35%), were prevented by PSMA PET; 73 tests, mostly biopsies (n = 44, 60%) as requested by the study protocol, were triggered (Q1/2). Conclusion: According to referring physicians, sites of recurrence were clarified by PSMA PET and disease localization translated into management changes in more than half of patients with biochemical recurrence of prostate cancer.

Background: The management for totally thyroidectomized differentiated thyroid cancer (TT-DTC) patients with unexplained hyperthyroglobulinemia remains indeterminate due to evidence scarcity. This multicenter study aimed at prospectively evaluating the response to radioiodine (¹³¹I) adjuvant therapy (RAT) and its potential role in risk stratification and causal clarification. Methods: TT-DTC patients with stimulated serum thyroglobulin (Tgoff) levels > 10 ng/mL but no structurally evident disease were consecutively enrolled in five tertiary care institutions. After the administration of 5.55 GBq of ¹³¹I, the risk of presence of persistent/recurrent/metastatic DTC (prmDTC) was compared to that before RAT. The causes of hyperthyroglobulinemia were explored and the response to RAT was assessed 6-12 months post RAT. The change in suppressed thyroglobulin (Tgon) level was reported. Results: A cohort of 254 subjects with a median Tgoff of 27.1 ng/mL was enrolled for the analyses. Immediately after RAT, low-, intermediate-, and high-risk were identified in 5.9%, 88.6%, and 5.5% patients, respectively, with no significant difference in risk stratification compared with that before RAT (P = 0.952). During the follow-up (median, 10.6 months), hyperthyroglobulinemia was ultimately attributed to thyroid remnant, biochemical disease, and structural/functional disease in 17.3%, 54.3%, and 28.3% of subjects, respectively. In addition, excellent, indeterminate, biochemical incomplete, and structural/functional incomplete responses were achieved in 18.1%, 27.2%, 36.2%, and 18.5% of patients, respectively. Notably, distribution for either cause of hyperthyroglobulinemia or response to RAT was comparable among the three postoperative risk groups. Tgon levels in patients who merely received RAT declined significantly over time. Conclusion: Our study demonstrated that over 90% of TT-DTC patients with unexplained hyperthyroglobulinemia are stratified as intermediate-high risk, and RAT using 5.55 GBq of ¹³¹I reveals biochemical/functional/structural disease and yields non-structural/functional incomplete response in more than 80% patients, suggesting TT-DTC patients with unexplained hyperthyroglobulinemia as explicit candidates for RAT.

Treatment of hyperinsulinemic hypoglycemia is challenging. Surgical treatment of insulinomas and focal lesions in congenital hyperinsulinism (CHI) is invasive and carries major risks of morbidity. Medication to treat nesidioblastosis and diffuse CHI has varying efficacy and causes significant side effects. Here, we describe a novel method for therapy of hyperinsulinemic hyperglycemia, highly selectively killing beta cells by targeted photodynamic therapy (tPDT) with exendin-4-IRDye700DX, targeting the glucagon-like peptide 1 receptor (GLP-1R). A competitive binding assay was performed using Chinese hamster lung (CHL) cells transfected with the GLP-1R. The efficacy and specificity of tPDT with exendin-4-IRDye700DX was examined in vitro in cells with different levels of GLP-1R expression. Tracer biodistribution was determined in BALB/c nude mice bearing subcutaneous CHL-GLP-1R xenografts. Induction of cellular damage and the effect on tumor growth were analyzed to determine treatment efficacy. Exendin-4-IRDye700DX has a high affinity for the GLP-1R with an IC50 value of 6.3 nM. TPDT caused significant specific phototoxicity in GLP-1R positive cells (2.3 ± 0.8 % and 2.7 ± 0.3 % remaining cell viability in CHL-GLP-1R and INS-1 cells resp.). The tracer accumulates dose-dependently in GLP-1R positive tumors. In vivo tPDT induces cellular damage in tumors, shown by strong expression of cleaved-caspase-3 and leads to a prolonged median survival of the mice (36.5 vs. 22.5 days resp. p<0.05). These data show in vitro as well as in vivo evidence for the potency of tPDT using exendin-4-IRDye700DX. This could in the future provide a new, minimally invasive and highly specific treatment method for hyperinsulinemic hypoglycemia.

Rationale: To conduct a retrospective study comparing three ¹²³I-FP-CIT-SPECT quantitative methods in patients with neurodegenerative syndromes as referenced to neuropathological findings. Methods: ¹²³I-FP-CIT-SPECT and neuropathological findings among patients with neurodegenerative syndromes from the Mayo Alzheimer's Disease Research Center and Mayo Clinic Study of Aging were examined. Three ¹²³I-FP-CIT-SPECT quantitative assessment Methods: MIMneuro (MIM Software Inc.), DaTQUANT (GE Healthcare), and manual region of interest (ROI) creation on an Advantage Workstation (GE Healthcare) were compared to neuropathological findings describing the presence or absence of Lewy body disease (LBD). Striatum to background ratios (SBRs) generated by DaTQUANT were compared to the calculated SBRs of the manual method and MIMneuro. The left and right SBRs for caudate, putamen and striatum were evaluated with the manual method. For DaTQUANT and MIMneuro the left, right, total and average SBRs and z-scores for whole striatum, caudate, putamen, anterior putamen, and posterior putamen were calculated. Results: The cohort included 24 patients [20 (83%) male, aged 75.4 +/- 10.0 at death]. The antemortem clinical diagnoses were Alzheimer’s disease dementia (ADem, N = 6), probable dementia with Lewy bodies (pDLB, N = 12), mixed ADem/pDLB (N = 1), Parkinson’s disease with mild cognitive impairment (N = 2), corticobasal syndrome (N = 1), idiopathic rapid eye movement sleep behavior disorder (iRBD) (N = 1) and behavioral variant frontotemporal dementia (N = 1). Seventeen (71%) had LBD pathology. All three ¹²³I-FP-CIT-SPECT quantitative methods had area under the receiver operating characteristics (AUROC) values above 0.93 and up to 1.000 (p<0.001) and showed excellent discrimination between LBD and non-LBD patients in each region assessed, p<.001. There was no significant difference between the accuracy of the regions in discriminating the two groups, with good discrimination for both caudate and putamen. Conclusion: All three ¹²³I-FP-CIT-SPECT quantitative methods showed excellent discrimination between LBD and non-LBD patients in each region assessed, using both SBRs and z-scores.

The value of interim ¹⁸F-fluorodeoxyglucose positron emission tomography (iPET) guided treatment decisions in patients with diffuse large B-cell lymphoma (DLBCL) has been the subject of much debate. This investigation focuses on a comparison of the Deauville score and the deltaSUV_max (SUV_max) approach – two methods to assess early metabolic response to standard chemotherapy in DLBCL. Methods: Of 609 DLBCL patients participating in the Positron Emission Tomography-guided Therapy of Aggressive non-Hodgkin Lymphomas (PETAL) trial, iPET scans of 596 patients originally evaluated using the SUV_max method were available for post-hoc assessment of the Deauville score. A commonly used definition of an unfavorable iPET result according to the Deauville score is an uptake greater than that of the liver, whereas an unfavorable iPET scan with regard to the SUV_max approach is characterized as a relative reduction of the maximum standardized uptake value between baseline and iPET staging of less than or equal to 66%. We investigated the two methods’ correlation and concordance by Spearman’s rank correlation coefficient and the agreement in classification, respectively. We further used Kaplan-Meier curves and Cox regression to assess differences in survival between patient subgroups defined by the pre-specified cut-offs. Time-dependent receiver operating curve analysis provided information on the methods’ respective discrimination performance. Results: Deauville score and SUV_max approach differed in their iPET-based prognosis. The SUV_max approach outperformed the Deauville score in terms of discrimination performance – most likely due to a high number of false-positive decisions by the Deauville score. Cut-off-independent discrimination performance remained low for both methods, but cut-off-related analyses showed promising results. Both favored the SUV_max approach, e.g. for the segregation by iPET response, where the event-free survival hazard ratio was 3.14 (95% confidence interval (CI): 2.22 – 4.46) for SUV_max and 1.70 (95% CI: 1.29 – 2.24) for the Deauville score. Conclusion: When considering treatment intensification, the currently used Deauville score cut-off of an uptake above that of the liver seems to be inappropriate and associated with potential harm for DLBCL patients. The SUV_max criterion of a relative reduction of the maximum standardized uptake value of less than or equal to 66% should be considered as an alternative.

The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer (PCa). However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 biochemically recurrent PCa patients. Each subject served as his own control. [¹⁸F]DCFPyl PET/CT imaging sessions were performed 3 – 7 days apart, following oral administration of either 12.7 g of MSG or placebo. Data from the two sets of images were analyzed by placing regions of interest on lacrimal, parotid and submandibular glands, left ventricle, liver, spleen, kidneys, bowel, urinary bladder, gluteus muscle and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the ROI data. Results: A total of 142 pathological lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in maximal standardized uptake values corrected for lean body mass (SULmax) on images obtained following MSG administration in the parotids (24 ± 14%, P = 0.001), submandibular glands (35 ± 11%, P<0.001) and kidneys (23 ± 26%, P = 0.014). Significant decreases were also observed in lacrimal glands (49 ± 13%, P<0.001), liver (15 ± 6%, P<0.001), spleen (28 ± 13%, P = 0.001) and bowel (44 ± 13%, P<0.001). Mildly lower blood pool SULmean was observed after MSG administration (decrease of 11 ± 13%, P = 0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration compared to the placebo studies (SULmax median decrease 33%, range -1 to 75%, P<0.001). No significant adverse events occurred and vital signs were stable following placebo or MSG administration. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney and other normal organ PSMA radiotracer uptake in human subjects, using [¹⁸F]DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications.

Invitation Only Research Event

Event participants

Abebe Aemro Selassie, Director, African Department, International Monetary Fund
Chair: Elizabeth Donnelly, Deputy Head and Research Fellow, Africa Programme, Chatham House

Research Event

Event participants

Professor Stig Jarle Hansen, Professor, Norwegian University of Life Sciences; Author, Horn, Sahel and Rift: Fault-lines of the African Jihad
Bulama Bukarti, PhD Candidate, SOAS, University of London; Analyst, Tony Blair Institute for Global Change
Chair: Aoife McCullough, PhD Candidate, LSE

Research Event

Event participants

Professor Tony Chafer, University of Portsmouth
Professor Gordon Cumming, Cardiff University
Dr Roel van der Velde, Cardiff University
Ahmed Soliman, Research Fellow, Horn of Africa, Chatham House
Dr Elisa Lopez Lucia, Université Libre de Bruxelles; University of Portsmouth
Chair: Janet Adama Mohammed, West Africa Programme Director, Conciliation Resources

Research Event

Event participants

Louise Mushikiwabo, Secretary General, Organisation Internationale de la Francophonie (OIF)
Chair: Bob Dewar CMG, Associate Fellow, Africa Programme, Chatham House

31 October 2019

Trade between Central and Eastern Europe and sub-Saharan Africa has increased significantly in the last decade and a half. There is a strong case to be made for greater economic re-engagement, especially in terms of investment, that has the potential to support inclusive growth in both regions.

Members Event

Event participants

Carien du Plessis, Journalist; Co-Author, Understanding South Africa

James Hamill, Associate Fellow, International Institute for Strategic Studies; Author, Africa's Lost Leader: South Africa's Continental Role Since Apartheid

Martin Plaut, Senior Researcher, Institute of Commonwealth Studies; Co-Author, Understanding South Africa

Chair: Pumela Salela, UK Country Head, Brand South Africa 

6 November 2019 , Volume 95, Number 6

22 November 2019

Invitation Only Research Event

Event participants

Ambassador Mohamed Ali Guyo, IGAD Special Envoy for the Red Sea, Gulf of Aden and Somalia
Julian Reilly, UK Special Envoy for the Red Sea and Horn of Africa
Parfait Onanga-Anyanga, United Nations Special Envoy for the Horn of Africa
Alexander Rondos, EU Special Representative for the Horn of Africa
Chair: Susan Stigant, Director of Africa Programs, United States Institute of Peace

Invitation Only Research Event

Event participants

Professor Nick Binedell, Founding Director and Sasol Chair of Strategic Management, Gordon Institute of Business Science (GIBS), University of Pretoria

4 December 2019

10 December 2019

17 December 2019

18 December 2019

3 January 2020

Research Event

Research Event

Event participants

Helen Alderson, Head of Regional Delegation to UK and Ireland, International Committee of the Red Cross
Paul van Zyl, Co-Founder and Chief Creative Officer, The Conduit
Maya Marissa Malek, Chief Executive Officer, Amanie Advisors Global Office
Chair: Maram Ahmed, Senior Teaching Fellow, SOAS, University of London

Invitation Only Research Event

Event participants

Denise Brown, United Nations Deputy Special Representative of the Secretary-General, Resident and Humanitarian Coordinator in the Central African Republic
Chair: Ben Shepherd, Consulting Fellow, Africa Programme, Chatham House

Research Event

Event participants

Mohamed Guleid, Chief Executive Officer, Frontier Counties Development Council
Nuradin Dirie, Chair, Puntland Presidential Advisory Council
Aden Abdi, Horn of Africa Programme Director, Conciliation Resources
Chair: Dr Zahbia Yousuf, Senior Research Advisor, Saferworld 

Corporate Members Event

Event participants

Raj Kulasingam, Senior Counsel, Dentons

Megan McDonald, Head of Investment Banking (International), Standard Bank Group

Chair: Dr Alex Vines OBE, Managing Director, Ethics, Risk & Resilience; Director, Africa Programme, Chatham House

Research Event

Event participants

HE Nana Akufo-Addo, President of the Republic of Ghana
Chair: Dr Alex Vines OBE, Managing Director, Ethics, Risk & Resilience; Director, Africa Programme, Chatham House