Virtual breakfast: The state of the EU in 2023 3 May 2023 — 8:30AM TO 9:30AM Anonymous (not verified) 5 April 2023 Online

In this breakfast discussion, we will explore the current state of play in the EU with one the most prominent experts on European politics.

While the European Union has come together in its response to the invasion of Ukraine, significant divisions remain on other issues. East-West tensions remain high and troublesome German-French relations are hampering the bloc’s traditional engine of integration.
 
Furthermore, the EU is pushing through legislation at breakneck speed, including in its attempts to kickstart green industrial policy with its responses to the American Inflation Reduction Act. At the same time, the main players within the EU continue to disagree on what the bloc’s fiscal rules should look like.

• What are the implications of the recent wave of protests in France against President Macron’s pension reforms?
• What is the outlook of EU-UK relations following the successful completion of the Windsor Framework?
• Where are the fiscal rules likely to land and when will they be back in place?
• Are we seeing the emergence of a new Central and Eastern European power bloc within the EU?

In short, despite having avoided an energy crisis over the winter, the EU continues to face significant challenges. In this breakfast event, we will explore the current state of play in the EU with one of the most prominent experts on European politics.

C-X-C motif chemokine receptor 4 (CXCR4)–directed imaging has gained clinical interest in aiding clinical diagnostics in primary aldosteronism (PA). We retrospectively evaluated the feasibility of CXCR4-directed scintigraphy using the novel CXCR-4 ligand [^99mTc]Tc-pentixatec in patients with PA. Methods: Six patients (mean age ± SD, 49 ± 15 y) underwent CXCR4-directed scintigraphy (including planar imaging and SPECT/CT) 30, 120, and 240 min after injection of 435 ± 50 MBq of [^99mTc]Tc-pentixatec. Adrenal CXCR4 expression was analyzed by calculating lesion-to-contralateral ratios (LCRs). Imaging results were correlated to clinical information. Histopathology and clinical follow-up served as the standard of reference. Results: Three subjects showed lateralization of adrenal tracer accumulation, with a mean maximum lesion-to-contralateral ratio of 1.65 (range, 1.52–1.70), which correlated with morphologic findings on CT. One individual underwent adrenalectomy and presented with complete biochemical and clinical remission at follow-up. Histopathologic workup confirmed unilateral aldosterone-producing adenoma. Conclusion: [^99mTc]Tc-pentixatec scintigraphy with SPECT in patients with PA is feasible and might offer a valuable alternative to CXCR4-directed imaging with [⁶⁸Ga]Ga-pentixafor PET.

The peptide hormone ghrelin is produced in cardiomyocytes and acts through the myocardial growth hormone secretagogue receptor (GHSR) to promote cardiomyocyte survival. Administration of ghrelin may have therapeutic effects on post–myocardial infarction (MI) outcomes. Therefore, there is a need to develop molecular imaging probes that can track the dynamics of GHSR in health and disease to better predict the effectiveness of ghrelin-based therapeutics. We designed a high-affinity GHSR ligand labeled with ¹⁸F for imaging by PET and characterized its in vivo properties in a canine model of MI. Methods: We rationally designed and radiolabeled with ¹⁸F a quinazolinone derivative ([¹⁸F]LCE470) with subnanomolar binding affinity to GHSR. We determined the sensitivity and in vivo and ex vivo specificity of [¹⁸F]LCE470 in a canine model of surgically induced MI using PET/MRI, which allowed for anatomic localization of tracer uptake and simultaneous determination of global cardiac function. Uptake of [¹⁸F]LCE470 was determined by time–activity curve and SUV analysis in 3 regions of the left ventricle—area of infarct, territory served by the left circumflex coronary artery, and remote myocardium—over a period of 1.5 y. Changes in cardiac perfusion were tracked by [¹³N]NH₃ PET. Results: The receptor binding affinity of LCE470 was measured at 0.33 nM, the highest known receptor binding affinity for a radiolabeled GHSR ligand. In vivo blocking studies in healthy hounds and ex vivo blocking studies in myocardial tissue showed the specificity of [¹⁸F]LCE470, and sensitivity was demonstrated by a positive correlation between tracer uptake and GHSR abundance. Post-MI changes in [¹⁸F]LCE470 uptake occurred independently of perfusion tracer distributions and changes in global cardiac function. We found that the regional distribution of [¹⁸F]LCE470 within the left ventricle diverged significantly within 1 d after MI and remained that way throughout the 1.5-y duration of the study. Conclusion: [¹⁸F]LCE470 is a high-affinity PET tracer that can detect changes in the regional distribution of myocardial GHSR after MI. In vivo PET molecular imaging of the global dynamics of GHSR may lead to improved GHSR-based therapeutics in the treatment of post-MI remodeling.

Mutations of p53 protein occur in over half of all cancers, with profound effects on tumor biology. We present the first—to our knowledge—method for noninvasive visualization of p53 in tumor tissue in vivo, using SPECT, in 3 different models of cancer. Methods: Anti-p53 monoclonal antibodies were conjugated to the cell-penetrating transactivator of transcription (TAT) peptide and a metal ion chelator and then radiolabeled with ¹¹¹In to allow SPECT imaging. ¹¹¹In-anti-p53-TAT conjugates were retained longer in cells overexpressing p53-specific than non–p53-specific ¹¹¹In-mIgG (mouse IgG from murine plasma)-TAT controls, but not in null p53 cells. Results: In vivo SPECT imaging showed enhanced uptake of ¹¹¹In-anti-p53-TAT, versus ¹¹¹In-mIgG-TAT, in high-expression p53^R175H and medium-expression wild-type p53 but not in null p53 tumor xenografts. The results were confirmed in mice bearing genetically engineered KPC mouse–derived pancreatic ductal adenocarcinoma tumors. Imaging with ¹¹¹In-anti-p53-TAT was possible in KPC mice bearing spontaneous p53^R172H pancreatic ductal adenocarcinoma tumors. Conclusion: We demonstrate the feasibility of noninvasive in vivo molecular imaging of p53 in tumor tissue using a radiolabeled TAT-modified monoclonal antibody.

Preclinical data have shown that ¹⁶¹Tb-labeled peptides targeting the somatostatin receptor are therapeutically more effective for peptide receptor radionuclide therapy than are their ¹⁷⁷Lu-labeled counterparts. To further substantiate this enhanced therapeutic effect, we performed cellular dosimetry to quantify the absorbed dose to the cell nucleus and compared dose–response curves to evaluate differences in relative biological effectiveness in vitro. Methods: CA20948 cell survival was assessed after treatment with [¹⁶¹Tb]Tb- and [¹⁷⁷Lu]Lu-DOTATATE (agonist) and with [¹⁶¹Tb]Tb- and [¹⁷⁷Lu]Lu-DOTA-LM3 (antagonist) via a clonogenic assay. Cell binding, internalization, and dissociation assays were performed up to 7 d to acquire time-integrated activity coefficients. Separate S values for each type of particle emission (Auger/internal conversion [IC] electrons and β^– particles) were computed via Monte Carlo simulations, while considering spheric cells. Once the absorbed dose to the cell nucleus was calculated, survival curves were fitted to the appropriate linear or linear-quadratic model and corresponding relative biological effectiveness was evaluated. Results: Although the radiopeptide uptake was independent of the radionuclide, [¹⁶¹Tb]Tb-DOTATATE and [¹⁶¹Tb]Tb-DOTA-LM3 delivered a 3.6 and 3.8 times higher dose to the nucleus, respectively, than their ¹⁷⁷Lu-labeled counterparts on saturated receptor binding. This increased nucleus-absorbed dose was mainly due to the additional emission of IC and not Auger electrons by ¹⁶¹Tb. When activity concentrations were considered, both [¹⁶¹Tb]Tb-DOTATATE and [¹⁶¹Tb]Tb-DOTA-LM3 showed a lower survival fraction than did labeling with ¹⁷⁷Lu. When the absorbed dose to the nucleus was considered, no significant difference could be observed between the dose–response curves for [¹⁶¹Tb]Tb- and [¹⁷⁷Lu]Lu-DOTATATE. [¹⁶¹Tb]Tb-DOTA-LM3 showed a linear-quadratic dose response, whereas [¹⁶¹Tb]Tb-DOTATATE showed only a linear dose response within the observed dose range, suggesting additional cell membrane damage by Auger electrons. Conclusion: The IC, rather than Auger, electrons emitted by ¹⁶¹Tb resulted in a higher absorbed dose to the cell nucleus and lower clonogenic survival for [¹⁶¹Tb]Tb-DOTATATE and [¹⁶¹Tb]Tb-DOTA-LM3 than for the ¹⁷⁷Lu-labeled analogs. In contrast, [¹⁶¹Tb]Tb-DOTATATE showed no higher dose response than [¹⁷⁷Lu]Lu-DOTATATE, whereas for [¹⁶¹Tb]Tb-DOTA-LM3 an additional quadratic response was observed. Because of this quadratic response, potentially caused by cell membrane damage, [¹⁶¹Tb]Tb-DOTA-LM3 is a more effective radiopeptide than [¹⁶¹Tb]Tb-DOTATATE for labeling with ¹⁶¹Tb.

Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic - and β-emitting isotope ¹⁷⁷Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. Methods: Gemini was synthesized by linking 2 S-2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker. [¹⁷⁷Lu]Lu-Gemini was prepared with no-carrier-added ¹⁷⁷LuCl₃ to a molar-specific activity of 123 GBq/μmol and radiochemical purity of more than 99%. The specificity of BsAb-¹⁷⁷Lu-Gemini was verified in vitro. Subsequently, we evaluated biodistribution and whole-body clearance for [¹⁷⁷Lu]Lu-Gemini and, for comparison, our gold-standard monovalent [¹⁷⁷Lu]Lu-S-2-(4-aminobenzyl)-DOTA ([¹⁷⁷Lu]Lu-DOTA-Bn) in naïve (tumor-free) athymic nude mice. For our proof-of-concept system, a 3-step pretargeting approach was performed with an established DOTA-PRIT regimen (anti-GPA33/anti-DOTA IgG-scFv BsAb, a clearing agent, and [¹⁷⁷Lu]Lu-Gemini) in mouse models. Results: Initial in vivo studies showed that [¹⁷⁷Lu]Lu-Gemini behaved similarly to [¹⁷⁷Lu]Lu-DOTA-Bn, with almost identical blood and whole-body clearance kinetics, as well as biodistribution and mouse kidney dosimetry. Pretargeting [¹⁷⁷Lu]Lu-Gemini to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [¹⁷⁷Lu]Lu-Gemini for blood, tumor, liver, spleen, and kidneys of 3.99, 455, 6.93, 5.36, and 14.0 cGy/MBq, respectively. Tumor–to–normal tissue absorbed-dose ratios (i.e., therapeutic indices [TIs]) for the blood and kidneys were 114 and 33, respectively. In addition, we demonstrate that the use of bivalent [¹⁷⁷Lu]Lu-Gemini in DOTA-PRIT leads to improved TIs and augmented [¹⁷⁷Lu]Lu-Gemini tumor uptake and retention in comparison to monovalent [¹⁷⁷Lu]Lu-DOTA-Bn. Finally, we established efficacy in SW1222 tumor-bearing mice, demonstrating that a single injection of anti-GPA33 DOTA-PRIT with 44 MBq (1.2 mCi) of [¹⁷⁷Lu]Lu-Gemini (estimated tumor-absorbed dose, 200 Gy) induced complete responses in 5 of 5 animals and a histologic cure in 2 of 5 (40%) animals. Moreover, a significant increase in survival compared with nontreated controls was noted (maximum tolerated dose not reached). Conclusion: We have developed a bivalent DOTA-radiohapten, [¹⁷⁷Lu]Lu-Gemini, that showed improved radiopharmacology for DOTA-PRIT application. The use of bivalent [¹⁷⁷Lu]Lu-Gemini in DOTA-PRIT, as opposed to monovalent [¹⁷⁷Lu]Lu-DOTA-Bn, allows curative treatments with considerably less administered ¹⁷⁷Lu activity while still achieving high TIs for both the blood (>100) and the kidneys (>30).

Fibroblast activation protein (FAP) is abundantly expressed in the stroma of most human solid tumors. Clinical-stage radiolabeled FAP ligands are increasingly used as tools for the detection of various cancer lesions. To unleash the full therapeutic potential of FAP-targeting agents, ligands need to remain at the tumor site for several days after administration. We recently described the discovery of OncoFAP, a high-affinity small organic ligand of FAP with a rapid accumulation in tumors and low uptake in healthy tissues in cancer patients. Trimerization of OncoFAP provided a derivative (named TriOncoFAP, or OncoFAP-23) with improved FAP affinity. In this work, we evaluated the tissue biodistribution profile and the therapeutic performance of OncoFAP-23 in tumor-bearing mice. Methods: OncoFAP-23 was radiolabeled with the theranostic radionuclide ¹⁷⁷Lu. Preclinical experiments were conducted on mice bearing SK-RC-52.hFAP (BALB/c nude mice) or CT-26.hFAP (BALB/c mice) tumors. ¹⁷⁷Lu-OncoFAP and ¹⁷⁷Lu-FAP-2286 were included in the biodistribution study as controls. Toxicologic evaluation was performed on Wistar rats and CD1 mice by injecting high doses of OncoFAP-23 or its cold-labeled counterpart, respectively. Results: ¹⁷⁷Lu-OncoFAP-23 emerged for its best-in-class biodistribution profile, high and prolonged tumor uptake (i.e., ~16 percentage injected dose/g at 96 h), and low accumulation in healthy organs, which correlates well with its potent single-agent anticancer activity at low levels of administered radioactivity. Combination treatment with the tumor-targeted interleukin 2 (L19-IL2, a clinical-stage immunocytokine) further expands the therapeutic window of ¹⁷⁷Lu-OncoFAP-23 by potentiating its in vivo antitumor activity. Proteomics studies revealed a potent tumor-directed immune response on treatment with the combination. OncoFAP-23 and ^natLu-OncoFAP-23 exhibited a favorable toxicologic profile, without showing any side effects or signs of toxicity. Conclusion: OncoFAP-23 presents enhanced tumor uptake and tumor retention and low accumulation in healthy organs, findings that correspond to a strongly improved in vivo antitumor efficacy. The data presented in this work support the clinical development of ¹⁷⁷Lu-OncoFAP-23 for the treatment of FAP-positive solid tumors.

Our objective is to explore quantitative imaging markers for early prediction of treatment response in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) undergoing [¹⁷⁷Lu]Lu-DOTATATE therapy. By doing so, we aim to enable timely switching to more effective therapies in order to prevent time-resource waste and minimize toxicities. Methods: Patients diagnosed with unresectable or metastatic, progressive, well-differentiated, receptor-positive GEP-NETs who received 4 sessions of [¹⁷⁷Lu]Lu-DOTATATE were retrospectively selected. Using SPECT/CT images taken at the end of treatment sessions, we counted all visible tumors and measured their largest diameters to calculate the tumor burden score (TBS). Up to 4 target lesions were selected and semiautomatically segmented. Target lesion peak counts and spleen peak counts were measured, and normalized peak counts were calculated. Changes in TBS (TBS) and changes in normalized peak count (nPC) throughout treatment sessions in relation to the first treatment session were calculated. Treatment responses were evaluated using third-month CT and were binarized as progressive disease (PD) or non-PD. Results: Twenty-seven patients were included (7 PD, 20 non-PD). Significant differences were observed in TBS_second-first, TBS_third-first, and TBS_fourth-first (where second-first, third-first, and fourth-first denote scan number between the second and first, third and first, and fourth and first [¹⁷⁷Lu]Lu-DOTATATE treatment cycles), respectively) between the PD and non-PD groups (median, 0.043 vs. –0.049, 0.08 vs. –0.116, and 0.109 vs. –0.123 [P = 0.023, P = 0.002, and P < 0.001], respectively). nPC_second-first showed significant group differences (mean, –0.107 vs. –0.282; P = 0.033); nPC_third-first and nPC_fourth-first did not reach statistical significance (mean, –0.122 vs. –0.312 and –0.183 vs. –0.405 [P = 0.117 and 0.067], respectively). At the optimal threshold, TBS_fourth-first exhibited an area under the curve (AUC) of 0.957, achieving 100% sensitivity and 80% specificity. TBS_second-first and TBS_third-first reached AUCs of 0.793 and 0.893, sensitivities of 71.4%, and specificities of 85% and 95%, respectively. nPC_second-first, nPC_third-first, and nPC_fourth-first showed AUCs of 0.764, 0.693, and 0.679; sensitivities of 71.4%, 71.4%, and 100%; and specificities of 75%, 70%, and 35%, respectively. Conclusion: TBS and nPC can predict [¹⁷⁷Lu]Lu-DOTATATE response by the second treatment session.

Single-domain antibodies (sdAbs) demonstrate favorable pharmacokinetic profiles for molecular imaging applications. However, their renal excretion and retention are obstacles for applications in targeted radionuclide therapy (TRT). Methods: Using a click-chemistry–based pretargeting approach, we aimed to reduce kidney retention of a fibroblast activation protein α (FAP)–targeted sdAb, 4AH29, for ¹⁷⁷Lu-TRT. Key pretargeting parameters (sdAb-injected mass and lag time) were optimized in healthy mice and U87MG (FAP⁺) xenografts. A TRT study in a pancreatic ductal adenocarcinoma (PDAC) patient-derived xenograft (PDX) model was performed as a pilot study for sdAb-based pretargeting applications. Results: Modification of 4AH29 with trans-cyclooctene (TCO) moieties did not modify the sdAb pharmacokinetic profile. A 200-µg injected mass of 4AH29-TCO and an 8-h lag time for the injection of [¹⁷⁷Lu]Lu-DOTA-PEG₇-tetrazine resulted in the highest kidney therapeutic index (2.0 ± 0.4), which was 5-fold higher than that of [¹⁷⁷Lu]Lu-DOTA-4AH29 (0.4 ± 0.1). FAP expression in the tumor microenvironment was validated in a PDAC PDX model with both immunohistochemistry and PET/CT imaging. Mice treated with the pretargeting high-activity approach (4AH29-TCO + [¹⁷⁷Lu]Lu-DOTA-PEG₇-tetrazine; 3 x 88 MBq, 1 injection per week for 3 wk) demonstrated prolonged survival compared with the vehicle control and conventionally treated ([¹⁷⁷Lu]Lu-DOTA-4AH29; 3 x 37 MBq, 1 injection per week for 3 wk) mice. Mesangial expansion was reported in 7 of 10 mice in the conventional cohort, suggesting treatment-related kidney morphologic changes, but was not observed in the pretargeting cohort. Conclusion: This study validates pretargeting to mitigate sdAbs’ kidney retention with no observation of morphologic changes on therapy regimen at early time points. Clinical translation of click-chemistry–based pre-TRT is warranted on the basis of its ability to alleviate toxicities related to biovectors’ intrinsic pharmacokinetic profiles. The absence of representative animal models with extensive stroma and high FAP expression on cancer-associated fibroblasts led to a low mean tumor-absorbed dose even with high injected activity and consequently to modest survival benefit in this PDAC PDX.

Cancer of unknown primary (CUP) represents a heterogeneous group of metastatic tumors for which standardized diagnostic work-up fails to identify the primary site. We aimed to describe the Peter MacCallum Cancer Centre experience with ¹⁸F-FDG PET/CT in extracervical CUP with respect to detection of a primary site and its impact on management. A secondary aim was to compare overall survival (OS) in patients with and without a detected primary site. Methods: CUP patients treated between 2014 and 2020 were identified from medical oncology clinics and ¹⁸F-FDG PET/CT records. Information collated from electronic medical records included the suspected primary site and treatment details before and after ¹⁸F-FDG PET/CT. Clinicopathologic details and genomic analysis were used to determine the clinically suspected primary site and compared against 2 independent masked reads of ¹⁸F-FDG PET/CT images by nuclear medicine specialists to determine sensitivity, specificity, accuracy, and the rate of detection of the primary site. Results: We identified 147 patients, 65% of whom had undergone molecular profiling. The median age at diagnosis was 61 y (range, 20–84 y), and the median follow-up time was 74 mo (range, 26–83 mo). Eighty-two percent were classified as having an unfavorable CUP subtype as per international guidelines.¹⁸F-FDG PET/CT demonstrated a primary site detection rate of 41%, resulted in a change in management in 22%, and identified previously occult disease sites in 37%. Median OS was 16.8 mo for all patients and 104.7 and 12.1 mo for favorable and unfavorable CUP subtypes, respectively (P < 0.0001). Median OS in CUP patients when using ¹⁸F-FDG PET/CT, clinicopathologic, and genomic information was 19.8 and 8.5 mo when a primary site was detected and not detected, respectively (P = 0.016). Multivariable analysis of survival adjusted for age and sex remained significant for identification of a potential primary site (P < 0.001), a favorable CUP (P < 0.001), and an Eastern Cooperative Oncology Group status of 1 or less (P < 0.001). Conclusion: ¹⁸F-FDG PET/CT plays a complementary role in CUP diagnostic work-up and was able to determine the likely primary site in 41% of cases. OS is improved with primary site identification, demonstrating the value of access to diagnostic ¹⁸F-FDG PET/CT for CUP patients.

This study evaluates the diagnostic utility of PET/MRI for primary, locoregional, and nodal head and neck squamous cell carcinoma (HNSCC) through systematic review and metaanalysis. Methods: A systematic search was conducted using PubMed and Scopus to identify studies on the diagnostic accuracy of PET/MRI for HNSCC. The search included specific terms and excluded nonhybrid PET/MRI studies, and those with a sample size of fewer than 10 patients were excluded. Results: In total, 15 studies encompassing 638 patients were found addressing the diagnostic test accuracy for PET/MRI within the chosen subject domain. Squamous cell carcinoma of the nasopharynx was the most observed HNSCC subtype (n = 198). The metaanalysis included 12 studies, with pooled sensitivity and specificity values of 93% and 95% per patient for primary disease evaluation, 93% and 96% for locoregional evaluation, and 89% and 98% per lesion for nodal disease detection, respectively. An examination of a subset of studies comparing PET/MRI against PET/CT or MRI alone for evaluating nodal and locoregional HNSCC found that PET/MRI may offer slightly higher accuracy than other modalities. However, this difference was not statistically significant. Conclusion: PET/MRI has excellent potential for identifying primary, locoregional, and nodal HNSCC.

Tumor hypoxia, an integral biomarker to guide radiotherapy, can be imaged with ¹⁸F-fluoromisonidazole (¹⁸F-FMISO) hypoxia PET. One major obstacle to its broader application is the lack of standardized interpretation criteria. We sought to develop and validate practical interpretation criteria and a dedicated training protocol for nuclear medicine physicians to interpret ¹⁸F-FMISO hypoxia PET. Methods: We randomly selected 123 patients with human papillomavirus–positive oropharyngeal cancer enrolled in a phase II trial who underwent 123 ¹⁸F-FDG PET/CT and 134 ¹⁸F-FMISO PET/CT scans. Four independent nuclear medicine physicians with no ¹⁸F-FMISO experience read the scans. Interpretation by a fifth nuclear medicine physician with over 2 decades of ¹⁸F-FMISO experience was the reference standard. Performance was evaluated after initial instruction and subsequent dedicated training. Scans were considered positive for hypoxia by visual assessment if ¹⁸F-FMISO uptake was greater than floor-of-mouth uptake. Additionally, SUV_max was determined to evaluate whether quantitative assessment using tumor-to-background ratios could be helpful to define hypoxia positivity. Results: Visual assessment produced a mean sensitivity and specificity of 77.3% and 80.9%, with fair interreader agreement ( = 0.34), after initial instruction. After dedicated training, mean sensitivity and specificity improved to 97.6% and 86.9%, with almost perfect agreement ( = 0.86). Quantitative assessment with an estimated best SUV_max ratio threshold of more than 1.2 to define hypoxia positivity produced a mean sensitivity and specificity of 56.8% and 95.9%, respectively, with substantial interreader agreement ( = 0.66), after initial instruction. After dedicated training, mean sensitivity improved to 89.6% whereas mean specificity remained high at 95.3%, with near-perfect interreader agreement ( = 0.86). Conclusion: Nuclear medicine physicians without ¹⁸F-FMISO hypoxia PET reading experience demonstrate much improved interreader agreement with dedicated training using specific interpretation criteria.

Bispecific antibodies (bsAbs) are engineered to target 2 different epitopes simultaneously. About 75% of the 16 clinically approved bsAbs have entered the clinic internationally since 2022. Hence, research on biomedical imaging of various radiolabeled bsAb scaffolds may serve to improve patient selection for bsAb therapy. Here, we provide a comprehensive overview of recent advances in radiolabeled bsAbs for imaging via PET or SPECT. We compare direct targeting and pretargeting approaches in preclinical and clinical studies in oncologic research. Furthermore, we show preclinical applications of imaging bsAbs in neurodegenerative diseases. Finally, we offer perspectives on the future directions of imaging bsAbs based on their challenges and opportunities.

Following early acceptance by urologists, the use of surgical robotic platforms is rapidly spreading to other surgical fields. This empowerment of surgical perception via robotic advances occurs in parallel to developments in intraoperative molecular imaging. Convergence of these efforts creates a logical incentive to advance the decades-old image-guided robotics paradigm. This yields new radioguided surgery strategies set to optimally exploit the symbiosis between the growing clinical translation of robotics and molecular imaging. These strategies intend to advance surgical precision by increasing dexterity and optimizing surgical decision-making. In this state-of-the-art review, topic-related developments in chemistry (tracer development) and engineering (medical device development) are discussed, and future scientific robotic growth markets for molecular imaging are presented.

Taking Stock of Turkey's Trade Policy 11 September 2018 — 5:00PM TO 6:15PM Anonymous (not verified) 23 August 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

As the only large economy outside of the EU with a customs union agreement, Turkey has a unique trade policy. Amid domestic economic challenges, Turkey’s trade minister, Ruhsar Pekcan, will discuss prospects for upgrading the EU-Turkey customs union. She will also discuss relations between the UK and Turkey and outline strategies for post-Brexit trade.

Attendance at this event is by invitation only.

Turkey's Foreign Policy: The Perspective of the Main Opposition Party 5 November 2020 — 12:00PM TO 1:00PM Anonymous (not verified) 14 October 2020 Online

The Republican People’s Party (CHP), the main Turkish opposition party, is becoming a serious contender for a leading role in the country’s politics.

This is an online only event.

CHP’s mayoral candidates defeated the Justice and Development Party (AKP) incumbents in the 2019 local elections in Ankara and Istanbul, which held both cities for a quarter of a century. Its ascendency in Turkish politics is improving prospects for a CHP-led government after the next general election in 2023.

In this webinar, the speaker will share CHP’s stance on the country’s foreign policy towards key regional allies in Europe, as well as its take on relations with Russia, the US and Turkey’s position and role in the Middle East. Finally, the speaker will share how CHP’s external policy might differ from the ruling AKP. 

Turkey-Russia Relations: A Marriage of Convenience? 26 November 2020 — 12:00PM TO 1:30PM Anonymous (not verified) 17 November 2020 Chatham House

Speakers discuss the complex but, so far, durable ties between Putin and Erdogan and the perspectives of each leader. Other issues will include the impact of the Biden presidency and the unfolding situation in Nagorny Karabakh.

This is an online only event

Russia-Turkey relations are governed by a unique dynamic between presidents Vladimir Putin and Recep Tayyip Erdogan. They pursue contrasting objectives in Libya, the Eastern Mediterranean, Caucasus and Ukraine; yet they have managed to compartmentalize their differences to avoid any spill-over into diplomatic, military and economic cooperation.

Erdogan purchased the Russian S400 missile defence system at the cost of ejection from the US-led fourth generation F35 stealth fighter programme; and at the risk of sanctions by Washington. Russia is also proceeding with the construction of the Akkuyu Nuclear Power Plant near Turkey’s Mediterranean coast.

Turkey's foreign policy: The perspective of the İYİ Parti 25 January 2021 — 12:00PM TO 1:00PM Anonymous (not verified) 14 January 2021 Online

The centre-right İYİ Parti, the second largest opposition party in Turkey, is attracting voters from the governing alliance between the Justice and Development Party (AKP) and the pro-Turkish National Movement Party (MHP).

Please complete your registration on Zoom:

The İYİ Parti, which was set up in 2017, formed the Nation Alliance (Millet İttifakı) with the left-of-centre Republican People’s Party (CHP) and the pro-Islam Felicity Party (Saadet Partisi) in the 2018 parliamentary elections winning 43 seats in the Grand National Assembly.

In the 2019 municipal elections, the İYİ Parti’s alliance alliance with the CHP played an important role in enabling the latter’s candidates to become the mayors of Istanbul and Ankara after a quarter-century dominance by the ruling Justice and Development Party (AKP).

Its popularity has been rising steadily, according to recent polls. In this webinar, the speaker will outline the party’s viewpoint on the country’s foreign policy towards the European Union, as well as its perspectives on relations with Russia, the US, Iran and the Arab world. Finally, he will share the ways in which the İYİ Parti’s approach to external policy might differ from the ruling AKP.

Turkey’s foreign and domestic policy: A story of mutual creation? 1 November 2022 — 2:00PM TO 3:00PM Anonymous (not verified) 12 October 2022 Online

Panellists discuss the link between Turkey’s domestic and foreign policies under President Erdoğan.

From Turkey’s ongoing rapprochement with its erstwhile Middle Eastern antagonists to its Syria policy and earlier approach towards the West, there has been extensive discussion on the domestic drivers behind Ankara’s foreign policy.

Less discussed but no less important is how Turkish foreign affairs have shaped its internal politics. Under the rule of the Justice and Development Party (AKP) government and President Recep Tayyip Erdoğan, Turkey’s foreign and domestic policies have mutually reshaped each other.

In this webinar, launching Gönül Tol’s new book Erdoğan’s War: A Strongman’s Struggle at Home and in Syria, panellists will take stock of how Turkey’s domestic and foreign policies under the leadership of President Erdoğan have influenced and shaped each other. Speakers will also discuss the internal drivers behind Turkey’s current reset in relations with the Middle East, and examine how Ankara’s foreign affairs play into the country’s political and identity fault lines.

The event will be held on the record and will be live-streamed on the MENA Programme’s Facebook page.

Officials in Mexico and across Latin America are anxiously watching the outcome of Tuesday's U.S. Presidential contest in light of GOP candidate Donald Trump's campaign promise to "deport 11 million criminal aliens."

A Qantas airlines flight made an emergency landing at Sydney Airport on Friday afternoon after suffering engine failure shortly after takeoff, the company said.

Genetic-testing lab 23andMe plans to cut its workforce by 40% and end its therapeutics program in an effort to cut costs, the company announced Monday.

Costco voluntarily recalled 79,200 pounds of two types of its store-brand butter over the past month because their labels may not have said the products contain milk.

President-elect Donald Trump announced Tuesday that Elon Musk and Vivek Ramaswamy will lead his administration's new Department of Government Efficiency, or DOGE, to end "government waste" and "slash excess regulations."

This is a Remote Eligible open rank research software engineer position. The OIT (Office of Information Technology) department, Home | Office of Information Technology (oit.gatech.edu) at the Georgia Institute of Technology in Atlanta, Georgia invites applications for Partnership for Advanced Computing Environment (PACE) (pace.gatech.edu). This is a research faculty position, applications will be considered at all ranks. We seek a highly skilled and innovative Research Scientist to join our research software engineer team. The successful candidate will lead software lifecycle management with security and compliance efforts in PACE, in collaboration with other researchers, play a key role in supporting sensitive/regulated research projects while ensuring compliance with applicable regulations and security requirements. This position will also be responsible for the PACE software vulnerability management program. This role will closely work with the Research Facilitation and Cyberinfrastructure Teams to bring support to GT faculty on regulated research projects and evaluate underlying technologies. This role requires strong software engineering expertise, excellent communication skills, and the ability to bring innovative solutions to researchers’ projects and implement them to deliverable. Responsibilities • Define and implement standard operating procedures to incorporate software vulnerability management • Coordinate with other cyber security and research security personnel to satisfy software audit and compliance requirements • Software Bill of Materials (SBOM) management, identify and address software vulnerability for the PACE software stack • Take responsibility for the audit and compliance of restricted software/code (e.g. RSICC/NASA) • Provide domain expertise on CUI (Controlled Unclassified Information) and regulated software • Provide support on commercial/licensed software in the regulated environment • Work in partnership with other GT Colleges’ IT groups to support the deployment of HPC scientific applications and workflows for researchers on PACE systems • Closely work with other internal PACE units, including the Research Computing Facilitation (RCF) and Cyberinfrastructure (CI) teams, to address researchers’ needs • Coordinate review and software access processes with other research cyber security personnel • Implement best practices around research computing software vulnerability management • Research and evaluate any new technologies in software vulnerability and closely monitor NIST regulations • Author and publish scientific papers, reports, and presentations to communicate research results and findings to internal and external audiences

SAN JOSE, Calif., Oct. 16, 2024 — Supermicro, Inc. is launching a new optimized storage system for high performance AI training, inference and HPC workloads. This JBOF (Just a Bunch […]

The post Supermicro Introduces JBOF Storage Platform Powered by NVIDIA BlueField-3 for Scalable AI and HPC appeared first on HPCwire.

Oct. 24, 2024 — The San Diego Supercomputer Center (SDSC), part of the School of Computing, Information and Data Sciences at UC San Diego, has been leading the Open Storage Network (OSN) program for years, and along […]

The post SDSC Leads Expansion of Open Storage Network to More Campus Computing Sites appeared first on HPCwire.

TEL AVIV, Israel and MINNEAPOLIS, Oct. 30, 2024 — NextSilicon, a pioneer in high-performance computing (HPC) innovation, today announced its emergence from stealth with the launch of Maverick-2, the industry’s first […]

The post NextSilicon Launches Maverick-2, Introducing Software-Defined Acceleration for HPC Workloads appeared first on HPCwire.

A hologram of a sex worker who was murdered in Amsterdam more than a decade ago could help solve the cold case, investigators hope.

A flight of Florida-based Spirit Airlines was hit by gunfire while attempting to land in Haiti with a crew member that sustained "minor injuries."

Zapata Computing, which was founded in 2017 as a Harvard spinout specializing in quantum software and later pivoted to an AI focus, is ceasing operations, according to an SEC filing […]

The post Zapata Computing, Early Quantum-AI Software Specialist, Ceases Operations appeared first on HPCwire.

RICHLAND, Wash.—Some computing challenges are so big that it’s necessary to go all in. That’s the approach a diverse team of scientists and computing experts led by the Department of Energy’s […]

The post PNNL-Microsoft Collaborate on Cloud Computing for Chemistry, More to Come appeared first on HPCwire.

Oregon, Ohio State, Georgia and Miami lead the first edition of the 2024-25 College Football Playoff rankings, the selection committee announced.

Billy Napier will remain in place as head football coach at Florida, despite the Gators producing another lackluster campaign during his third season, athletic director Scott Stricklin announced Thursday.

A struggling Detroit Lions offense awoke late, scoring 19-unanswered points to rally past the Houston Texans and improve to 8-1 this season. The Lions overcame a career-high five interceptions Jared Goff threw.

Lionel Messi said Inter Miami will get ready to "come back stronger next year" after the Herons' upset loss to Atlanta United in the first round of the 2024 MLS Cup playoffs.

Chicago Bears coach Matt Eberflus has fired offensive coordinator Shane Waldron, the team said Tuesday. The dismissal came less than a day after Eberflus committed to quarterback Caleb Williams, but promised "changes."

Last week NSF issued a request for the next round of proposals for its Quantum Leap Challenge Institutes (QLCI). First established in 2020, the QLCI program, as directed by National […]

The post NSF Seeks Proposals for Next Round of Quantum Leap Challenge Institutes appeared first on HPCwire.

PITTSBURGH, Sept. 24, 2024 — Ansys and TSMC today announced a successful pilot with Microsoft that significantly speeds-up the simulation and analysis of silicon photonic components. Together, the companies achieved […]

The post TSMC Collaborates with Ansys and Microsoft to Accelerate Photonic Simulations appeared first on HPCwire.

In this webinar, Martijn de Vries, CTO at Bright Computing and Robert Stober, Director of Product Management at Bright Computing, discuss the convergence of HPC and AI in the context […]

The post The Convergence of HPC and AI appeared first on HPCwire.

Raghunandan Mathur, Senior Systems Engineer, NEC, discusses now with modern day programming frameworks designed around the paradigms of scalar architectures and vector-like extensions, many present-day programmers expect a major learning […]

The post Ease of programming on NEC’s Vector Engine or SX-Aurora TSUBASA appeared first on HPCwire.

About This Webinar Oracle’s next generation HPC architecture with Intel compute instance based on 3rd Generation Intel® Xeon® Scalable processors, code named “Ice Lake”, changes the game for HPC in […]

The post Speed up Innovation with performance gains of up to 42% on the most powerful HPC Cloud appeared first on HPCwire.

A 77-year-old slice of cake from Queen Elizabeth II's wedding to Prince Philip was auctioned for $2,800.

The National Toy Hall of Fame in Rochester, N.Y., announced this year's inductees: My Little Pony, Transformers and Phase 10.

We hear a lot about quantum computers – sometimes too much – but not as much about quantum networking which will also be a critical component in making widespread use […]

The post EPB Offers Commercial Quantum Network for Quantum Developers appeared first on HPCwire.

Software implementation in high-performance computing is getting more fragmented as organizations opt for tools in their walled garden environments.  However, a new organization formed under the Linux Foundation could bring […]

The post Public and Private Sectors Team up to Solve HPC Software Problem  appeared first on HPCwire.

March 14, 2024 — Keysight Technologies, Inc. and Q-CTRL are partnering to integrate key infrastructure quantum software to accelerate quantum processor development, characterization, and key proof of principle scientific demonstrations. An interesting […]

The post Keysight and Q-CTRL Team Up to Accelerate Infrastructure Quantum Software appeared first on HPCwire.