Lila Iké’s latest single, ‘ I Spy’, is flirty and playful with a sultry tone. It’s the kind of song record labels in decades past would compulsorily conflate with bubblegum pop princess images of lollipops, pigtails, ribbons, and skirts with...

The global pandemic is real, with almost 8,000 deaths worldwide and nearly 200,000 persons having contracted the virus in 155 affected countries. What is particularly comforting for this country, amid pain and the not knowing, is the bedside and...

Aging-dependent changes in tissue function are associated with the development of metabolic diseases. However, the molecular connections linking aging, obesity, and diabetes remain unclear. Lamin A, lamin C, and progerin, products of the Lmna gene, have antagonistic functions on energy metabolism and life span. Lamin C, albeit promoting obesity, increases life span, suggesting that this isoform is crucial for maintaining healthy conditions under metabolic stresses. Because β-cell loss during obesity or aging leads to diabetes, we investigated the contribution of lamin C to β-cell function in physiopathological conditions. We demonstrate that aged lamin C only–expressing mice (Lmna^LCS/LCS) become obese but remain glucose tolerant due to adaptive mechanisms including increased β-cell mass and insulin secretion. Triggering diabetes in young mice revealed that Lmna^LCS/LCS animals normalize their fasting glycemia by both increasing insulin secretion and regenerating β-cells. Genome-wide analyses combined to functional analyses revealed an increase of mitochondrial biogenesis and global translational rate in Lmna^LCS/LCS islets, two major processes involved in insulin secretion. Altogether, our results demonstrate for the first time that the sole expression of lamin C protects from glucose intolerance through a β-cell–adaptive transcriptional program during metabolic stresses, highlighting Lmna gene processing as a new therapeutic target for diabetes treatment.

The host environment is a crucial factor for considering the transplant of stem cell–derived immature pancreatic cells in patients with type 1 diabetes. Here, we investigated the effect of insulin (INS)-deficient diabetes on the fate of immature pancreatic endocrine cell grafts and the underlying mechanisms. Human induced pluripotent stem cell–derived pancreatic endocrine progenitor cells (EPCs), which contained a high proportion of chromogranin A⁺ NK6 homeobox 1⁺ cells and very few INS⁺ cells, were used. When the EPCs were implanted under the kidney capsule in immunodeficient mice, INS-deficient diabetes accelerated increase in plasma human C-peptide, a marker of graft-derived INS secretion. The acceleration was suppressed by INS infusion but not affected by partial attenuation of hyperglycemia by dapagliflozin, an INS-independent glucose-lowering agent. Immunohistochemical analyses indicated that the grafts from diabetic mice contained more endocrine cells including proliferative INS-producing cells compared with that from nondiabetic mice, despite no difference in whole graft mass between the two groups. These data suggest that INS-deficient diabetes upregulates the INS-secreting capacity of EPC grafts by increasing the number of endocrine cells including INS-producing cells without changing the graft mass. These findings provide useful insights into postoperative diabetic care for cell therapy using stem cell–derived pancreatic cells.

Braves manager Brian Snitker joked that he could almost detect a smile as he shared a phone conversation with Nick Markakis after the stoic outfielder re-signed with the club in January. Snitker and others actually saw that smile on Tuesday morning, when Markakis reported to Spring Training to begin his fifth season with the Braves and attempt to push the club past the rebuild he positively enriched through his leadership.

Looking to preempt questions about his work ethic in a nightmare 2018 season, Chris Davis reported to Spring Training in Florida more than a week before Orioles position players were required to. That's when his efforts to rebound hit their first minor snag.

JOHANNESBURG (AP) — A virtual meeting of South African lawmakers has been disrupted by hackers who flooded the video call with pornographic images. In the incident on Thursday, the hackers also hurled racial and sexual insults at the meeting...

The UK’s austerity programme has disproportionately affected children and people with disabilities, says David Taylor-Robinson, a senior clinical lecturer in public health at the University of Liverpool. He joins us to discuss why the evidence shows the vulnerable are hit hardest by the cuts to public services, despite the UN conventions on...

Jackie Applebee is a GP in Tower Hamlets in London, and is concerned that the way the GP funding formula is working doesn't take account of the earlier health needs of people in deprived areas. For more about the Tower Hamlets Save Our Surgery campaign, visit their facebook page https://www.facebook.com/SaveOurGPsurgeries BMJ Voices is a...

Some apps have the potential to encourage healthier habits and are accessible to most people, argues Iltifat Husain, but Des Spence notes the lack of any evidence of effectiveness and the potential for encouraging unnecessary anxiety. Read more about in our head to head "Can healthy people benefit from health apps?" -...

The "internal market" was created after the 1987 UK general election focused attention on inadequate funding in the NHS, long waiting lists for elective surgery, and large unwarranted variations in clinical care. Economists attributed these problems to a lack of incentives for efficiency, and the remedies offered included increasing competition...

The European Medicines Agency (EMA) has embraced a new model of drug testing and marketing called “adaptive pathways”, allowing new drugs for “unmet medical needs” to be launched on the market faster, on the basis of fewer data. While industry claims this is necessary, an analysis on thebmj.com looks at the assumptions underlying the new pathway,...

Lily was diagnosed at 14 years old with stage four Hodgkin's lymphoma and received six rounds of chemotherapy and two weeks of radiotherapy. She survived but now lives with the long term effects of that therapy - and joins us to discuss how it has impacted her quality of life. We're also joined by Saif Ahmad and Thankamma Ajithkumar, oncologists...

Underneath all of our civilisation and science, we’re still primates - and the connection between patient and doctor can be reinforced by simply taking a hand. Robin Youngson, cofounder of hearts in healthcare, and Mitzi Blennerhassett, who has written extensively on patient engagement, have co-authored an editorial calling for the humanisation...

A study published by The BMJ today reports a possible association between intake of highly processed (“ultra-processed”) food in the diet and cancer. Ultra-processed foods include packaged baked goods and snacks, fizzy drinks, sugary cereals, ready meals and reconstituted meat products - often containing high levels of sugar, fat, and salt, but...

Sue Farrington is chair of the Patient Information Forum, a member organisation which promotes best practice in anyone who produces information for patients. In this podcast, she discusses what makes good patient information, why doctors should be pleased when patients arrive at an appointment with a long list of questions, and why patients are...

There is very little guidance on withdrawing or tapering opioids in chronic pain (not caused by cancer). People can fear pain, withdrawal symptoms, a lack of social and healthcare support, and they may also distrust non-opioid methods of pain management. This can mean that patients receive repeat opioid prescriptions for extended periods of...

Susan Greenhalg is a research professor of chinese society in Harvard’s department of anthropology - not a natural fit for a medical journal you may think, but recently she has been looking at the influence of Coca Cola on obesity policy in China. She has written up her investigation in an article published on bmj.com this week, and joins us in...

In this EBM round-up, Carl Heneghan, Helen Macdonald and Duncan Jarvies are back to give you an update Dual vs single therapy for prevention of TIA or minor stroke - how does the advice that dual work better translate in the UK? Carl explains why Japan can teach us to get active and, how GPs can use that information to "drop a decade" in...

Jönköping has been at the centre of the healthcare quality improvement movement for years - but how did a forested region of Sweden, situated between it's main cities, come to embrace the philosophy of improvement so fervently? Goran Henriks, chief executive of learning and innovation at Qulturum in Jönköping joins us to explain. He also tells...

Change requires the application of power - the way in which individuals can accrue power has shifted in our digitally connected world. Traditional ways of influencing change in healthcare (getting the chief executive on side, having a quiet chat with the medical director) are not the only way to build a momentum. Henry Timms - author of “New...

On the 7th of June, 1753, Dr Archibald Cameron was executed at Tyburn. "The body, after hanging twenty minutes, was cut down: it was not quartered; but the heart was taken out and burnt. " 250 years later, his sixth great grandson, Robert Syned found himself deeply involved in the process of execution, as an expert witness in a case about the use...

This week the Trump administration has banned the sale of flavoured vapes in the USA. The reason for that is the sudden rash of cases of pulmonary disease, including deaths, linked to vaping. The mechanism by which vaping may be causing damage to the lungs is as yet unclear, and our understanding is hampered by the heterogeneous nature of the...

Around half of trials that supported new cancer drug approvals in Europe between 2014 and 2016 were judged to be at high risk of bias, in a new study. Huseyin Naci,assistant professor of health policy a the London School of Economics joins us to talk about why potential bias may mean potential exaggeration of treatment effects, and could be...

Talk Evidence is back, with your monthly take on the world of EBM with Duncan Jarvies and GPs Carl Heneghan (also director for the Centre of Evidence Based Medicine at the University of Oxford) and Helen Macdonald (also The BMJ's UK research Editor). This month Carl talks about evidence that restricting your diet might improve health at a...

A UK general election has been called - polling day is on the 12th of December, and from now until then we’re going to be bringing you a weekly election-themed podcast. We want to help you make sense of the promises and pledges, claims and counter-claims, that are being made around healthcare and the NHS out on the campaign trail. This week has...

Katalin Susztak
Jan 1, 2006; 55:225-233
Complications

Samar I. Itani
Jul 1, 2002; 51:2005-2011
Rapid Publications

U.K. Prospective Diabetes Study Group
Nov 1, 1995; 44:1249-1258
Perspectives in Diabetes

Alexandra E. Butler
Jan 1, 2003; 52:102-110
Islet Studies

Children at increased genetic risk for type 1 diabetes (T1D) after environmental exposures may develop pancreatic islet autoantibodies (IA) at a very young age. Metabolic profile changes over time may imply responses to exposures and signal development of the first IA. Our present research in The Environmental Determinants of Diabetes in the Young (TEDDY) study aimed to identify metabolome-wide signals preceding the first IA against GAD (GADA-first) or against insulin (IAA-first). We profiled metabolomes by mass spectrometry from children’s plasma at 3-month intervals after birth until appearance of the first IA. A trajectory analysis discovered each first IA preceded by reduced amino acid proline and branched-chain amino acids (BCAAs), respectively. With independent time point analysis following birth, we discovered dehydroascorbic acid (DHAA) contributing to the risk of each first IA, and -aminobutyric acid (GABAs) associated with the first autoantibody against insulin (IAA-first). Methionine and alanine, compounds produced in BCAA metabolism and fatty acids, also preceded IA at different time points. Unsaturated triglycerides and phosphatidylethanolamines decreased in abundance before appearance of either autoantibody. Our findings suggest that IAA-first and GADA-first are heralded by different patterns of DHAA, GABA, multiple amino acids, and fatty acids, which may be important to primary prevention of T1D.

It was not the landing the Jamaicans who arrived at Kingston’s Norman Manley International Airport on Wednesday evening would want again. The 43 Jamaican ship workers of the Marella Discovery 2 were among the 115 people aboard the TUI charter flight that touched down amid the Kingston breeze and evening sunset.

THE EDITOR, Madam May is Child Month, and we, as parents, would show love and appreciation by taking out our kids for recreation, but instead, we have to keep them indoors because of a bush tiger called coronavirus. Every year at this time, I...

THE EDITOR, Madam: The Jamaican Government and local private-sector power brokers are still way behind and woefully lacking in investing, financially and otherwise, in Jamaica’s number one most powerful, most famous, most influential, and most...

As the global battle against the deadly COVID-19 disease wages on, with each country’s government, healthcare industry, and general public playing its part in defeating this new and relatively unknown enemy, two seemingly unlikely foot soldiers...

Reduced storage of dietary fatty acids (DFAs) in abdominal adipose tissues with enhanced cardiac partitioning has been shown in subjects with type 2 diabetes (T2D) and prediabetes. We measured DFA metabolism and organ partitioning using positron emission tomography with oral and intravenous long-chain fatty acid and glucose tracers during a standard liquid meal in 12 obese subjects with T2D before and 8–12 days after bariatric surgery (sleeve gastrectomy or sleeve gastrectomy and biliopancreatic diversion with duodenal switch). Bariatric surgery reduced cardiac DFA uptake from a median (standard uptake value [SUV]) 1.75 (interquartile range 1.39–2.57) before to 1.09 (1.04–1.53) after surgery (P = 0.01) and systemic DFA spillover from 56.7 mmol before to 24.7 mmol over 6 h after meal intake after surgery (P = 0.01), with a significant increase in intra-abdominal adipose tissue DFA uptake from 0.15 (0.04–0.31] before to 0.49 (0.20–0.59) SUV after surgery (P = 0.008). Hepatic insulin resistance was significantly reduced in close association with increased DFA storage in intra-abdominal adipose tissues (r = –0.79, P = 0.05) and reduced DFA spillover (r = 0.76, P = 0.01). We conclude that bariatric surgery in subjects with T2D rapidly reduces cardiac DFA partitioning and hepatic insulin resistance at least in part through increased intra-abdominal DFA storage and reduced spillover.

Diabetic retinopathy is the most common microvascular complication of diabetes, and in the advanced diabetic retinopathy appear vitreal fibrovascular membranes that consist of a variety of cells, including vascular endothelial cells (ECs). New therapeutic approaches for this diabetic complication are urgently needed. Here, we report that in cultured human retinal microvascular ECs, high glucose induced expression of p110, which was also expressed in ECs of fibrovascular membranes from patients with diabetes. This catalytic subunit of a receptor-regulated PI3K isoform is known to be highly enriched in leukocytes. Using genetic and pharmacological approaches, we show that p110 activity in cultured ECs controls Akt activation, cell proliferation, migration, and tube formation induced by vascular endothelial growth factor, basic fibroblast growth factor, and epidermal growth factor. Using a mouse model of oxygen-induced retinopathy, p110 inactivation was found to attenuate pathological retinal angiogenesis. p110 inhibitors have been approved for use in human B-cell malignancies. Our data suggest that antagonizing p110 constitutes a previously unappreciated therapeutic opportunity for diabetic retinopathy.

Clinical studies have suggested that changes in peripheral nerve microcirculation may contribute to nerve damage in diabetic polyneuropathy (DN). High-sensitivity troponin T (hsTNT) assays have been recently shown to provide predictive values for both cardiac and peripheral microangiopathy in type 2 diabetes (T2D). This study investigated the association of sciatic nerve structural damage in 3 Tesla (3T) magnetic resonance neurography (MRN) with hsTNT and N-terminal pro-brain natriuretic peptide serum levels in patients with T2D. MRN at 3T was performed in 51 patients with T2D (23 without DN, 28 with DN) and 10 control subjects without diabetes. The sciatic nerve’s fractional anisotropy (FA), a marker of structural nerve integrity, was correlated with clinical, electrophysiological, and serological data. In patients with T2D, hsTNT showed a negative correlation with the sciatic nerve’s FA (r = –0.52, P < 0.001), with a closer correlation in DN patients (r = –0.66, P < 0.001). hsTNT further correlated positively with the neuropathy disability score (r = 0.39, P = 0.005). Negative correlations were found with sural nerve conduction velocities (NCVs) (r = –0.65, P < 0.001) and tibial NCVs (r = –0.44, P = 0.002) and amplitudes (r = –0.53, P < 0.001). This study is the first to show that hsTNT is a potential indicator for structural nerve damage in T2D. Our results indirectly support the hypothesis that microangiopathy contributes to structural nerve damage in T2D.

25 November 2014

Japan's legality verification system, known as the goho-wood system, is not only voluntary but has serious design weaknesses which limit its ability to eliminate illegal products from Japan’s market.

25 November 2014

This paper accompanies a series of assessments on China, France, Japan, the Netherlands, the UK, the US and Vietnam, providing details on how the estimates of the level of illegality of imports of wood-based products into those countries were derived.

Invitation Only Research Event

Event participants

Dr Ashwini Swain, Fellow, CUTS Institute for Regulation and Competition
Glada Lahn, Senior Research Fellow, Energy, Environment and Resources, Chatham House
Dr Gareth Price, Senior Research Fellow, Asia Programme, Chatham House

Members Event

Event participants

Professor Dieter Helm CBE, Professor of Energy Policy, University of Oxford

Chair: David Shukman, Science Editor, BBC News

The present study examined the predictive values of amyloid PET, ¹⁸F-FDG PET, and nonimaging predictors (alone and in combination) for development of Alzheimer dementia (AD) in a large population of patients with mild cognitive impairment (MCI). Methods: The study included 319 patients with MCI from the Alzheimer Disease Neuroimaging Initiative database. In a derivation dataset (n = 159), the following Cox proportional-hazards models were constructed, each adjusted for age and sex: amyloid PET using ¹⁸F-florbetapir (pattern expression score of an amyloid-β AD conversion–related pattern, constructed by principle-components analysis); ¹⁸F-FDG PET (pattern expression score of a previously defined ¹⁸F-FDG–based AD conversion–related pattern, constructed by principle-components analysis); nonimaging (functional activities questionnaire, apolipoprotein E, and mini-mental state examination score); ¹⁸F-FDG PET + amyloid PET; amyloid PET + nonimaging; ¹⁸F-FDG PET + nonimaging; and amyloid PET + ¹⁸F-FDG PET + nonimaging. In a second step, the results of Cox regressions were applied to a validation dataset (n = 160) to stratify subjects according to the predicted conversion risk. Results: On the basis of the independent validation dataset, the ¹⁸F-FDG PET model yielded a significantly higher predictive value than the amyloid PET model. However, both were inferior to the nonimaging model and were significantly improved by the addition of nonimaging variables. The best prediction accuracy was reached by combining ¹⁸F-FDG PET, amyloid PET, and nonimaging variables. The combined model yielded 5-y free-of-conversion rates of 100%, 64%, and 24% for the low-, medium- and high-risk groups, respectively. Conclusion: ¹⁸F-FDG PET, amyloid PET, and nonimaging variables represent complementary predictors of conversion from MCI to AD. Especially in combination, they enable an accurate stratification of patients according to their conversion risks, which is of great interest for patient care and clinical trials.

We aimed to assess the value of ¹¹C-choline PET in patients with primary hyperparathyroidism and negative or discordant results on ^99mTc-sestamibi imaging and neck ultrasound. Methods: Eighty-seven such patients were assessed and subsequently underwent parathyroidectomy. PET/CT image data were analyzed semiquantitatively using SUV_max and SUV ratios (target to contralateral thyroid gland and carotid artery). A positive PET/CT result was defined as focal uptake significantly higher than regular thyroid tissue. Ectopic foci were also considered positive. Inconclusive PET/CT cases were defined as a lesion with uptake equal to normal thyroid tissue. If no prominent or ectopic uptake was detectable, the PET/CT result was considered negative. Results: When dichotomizing the ¹¹C-choline PET/CT imaging results by defining lesions with both positive and inconclusive uptake as positive, we found 84 of 92 lesions (91.3%) to have true-positive uptake whereas 8 lesions (8.7%) had false-positive uptake. One lesion showed false-negative uptake; the sensitivity was 98.8%. The corresponding positive predictive value for lesions was 91.3%. The mean SUV_max was 6.15 ± 4.92 in 72 lesions with positive uptake (70 patients) and 2.96 ± 2.32 in 20 lesions with inconclusive uptake (18 patients). Conclusion: These results in a large group of patients indicate that ¹¹C-choline PET/CT is a promising tool for parathyroid adenoma localization when ultrasound and ^99mTc-sestamibi imaging yield negative or discordant results.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder, definitive treatment usually requiring surgical removal of the offending parathyroid glands. To perform focused surgical approaches, it is necessary to localize all hyperfunctioning glands. The aim of the study was to compare the efficiency of established conventional scintigraphic imaging modalities with emerging ¹⁸F-fluorocholine PET/CT imaging in preoperative localization of hyperfunctioning parathyroid glands in a larger series of PHPT patients. Methods: In total, 103 patients with PHPT were imaged preoperatively with ¹⁸F-fluorocholine PET/CT and conventional scintigraphic imaging methods, consisting of ^99mTc-sestamibi SPECT/CT, ^99mTc-sestamibi/pertechnetate subtraction imaging, and ^99mTc-sestamibi dual-phase imaging. The results of histologic analysis, as well as intact parathyroid hormone and serum calcium values obtained 1 d after surgery and on follow-up, served as the standard of truth for evaluation of imaging results. Results: Diagnostic performance of ¹⁸F-fluorocholine PET/CT surpassed conventional scintigraphic methods (separately or combined), with calculated sensitivity of 92% for PET/CT and 39%–56% for conventional imaging (65% for conventional methods combined) in the entire patient group. Subgroup analysis, differentiating single and multiple hyperfunctioning parathyroid glands, showed PET/CT to be most valuable in the group with multiple hyperfunctioning glands, with sensitivity of 88%, whereas conventional imaging was significantly inferior, with sensitivity of 22%–34% (44% combined). Conclusion: ¹⁸F-fluorocholine PET/CT is a diagnostic modality superior to conventional imaging methods in patients with PHPT, allowing for accurate preoperative localization.

Fibroblast activation protein (FAP), which promotes tumor growth and progression, is overexpressed in cancer-associated fibroblasts of many human epithelial cancers. Because of its low expression in normal organs, FAP is an excellent target for theranostics. In this study, we used radionuclides with relatively long half-lives, ⁶⁴Cu (half-life, 12.7 h) and ²²⁵Ac (half-life, 10 d), to label FAP inhibitors (FAPIs) in mice with human pancreatic cancer xenografts. Methods: Male nude mice (body weight, 22.5 ± 1.2 g) were subcutaneously injected with human pancreatic cancer cells (PANC-1, n = 12; MIA PaCa-2, n = 8). Tumor xenograft mice were investigated after the intravenous injection of ⁶⁴Cu-FAPI-04 (7.21 ± 0.46 MBq) by dynamic and delayed PET scans (2.5 h after injection). Static scans 1 h after the injection of ⁶⁸Ga-FAPI-04 (3.6 ± 1.4 MBq) were also acquired for comparisons using the same cohort of mice (n = 8). Immunohistochemical staining was performed to confirm FAP expression in tumor xenografts using an FAP-α-antibody. For radioligand therapy, ²²⁵Ac-FAPI-04 (34 kBq) was injected into PANC-1 xenograft mice (n = 6). Tumor size was monitored and compared with that of control mice (n = 6). Results: Dynamic imaging of ⁶⁴Cu-FAPI-04 showed rapid clearance through the kidneys and slow washout from tumors. Delayed PET imaging of ⁶⁴Cu-FAPI-04 showed mild uptake in tumors and relatively high uptake in the liver and intestine. Accumulation levels in the tumor or normal organs were significantly higher for ⁶⁴Cu-FAPI-04 than for ⁶⁸Ga-FAPI-04, except in the heart, and excretion in the urine was higher for ⁶⁸Ga-FAPI-04 than for ⁶⁴Cu-FAPI-04. Immunohistochemical staining revealed abundant FAP expression in the stroma of xenografts. ²²⁵Ac-FAPI-04 injection showed significant tumor growth suppression in the PANC-1 xenograft mice, compared with the control mice, without a significant change in body weight. Conclusion: This proof-of-concept study showed that ⁶⁴Cu-FAPI-04 and ²²⁵Ac-FAPI-04 could be used in theranostics for the treatment of FAP-expressing pancreatic cancer. α-therapy targeting FAP in the cancer stroma is effective and will contribute to the development of a new treatment strategy.

Treatment of patients with advanced medullary thyroid carcinoma (MTC) is still a challenge. For more than 2 decades, it has been known that the cholecystokinin 2 receptor is a promising target for the treatment of MTC with radiolabeled minigastrin analogs. Unfortunately, kidney toxicity has precluded their therapeutic application so far. In 6 consecutive patients, we evaluated with advanced 3-dimensional dosimetry whether improved minigastrin analog ¹⁷⁷Lu-DOTA-(d-Glu)₆-Ala-Tyr-Gly-Trp-Nle-Asp-PheNH₂ (¹⁷⁷Lu-PP-F11N) is a suitable agent for the treatment of MTC. Methods: Patients received 2 injections of about 1 GBq (~80 μg) of ¹⁷⁷Lu-PP-F11N with and without a solution of succinylated gelatin (SG, a plasma expander used for nephroprotection) in a random crossover sequence to evaluate biodistribution, pharmacokinetics, and tumor and organ dosimetry. An electrocardiogram was obtained and blood count and blood chemistry were measured up to 12 wk after the administration of ¹⁷⁷Lu-PP-F11N to assess safety. Results: In all patients, ¹⁷⁷Lu-PP-F11N accumulation was visible in tumor tissue, stomach, and kidneys. Altogether, 13 tumors were eligible for dosimetry. The median absorbed doses for tumors, stomach, kidneys, and bone marrow were 0.88 (interquartile range [IQR]: 0.85–1.04), 0.42 (IQR: 0.25–1.01), 0.11 (IQR: 0.07–0.13), and 0.028 (IQR: 0.026–0.034) Gy/GBq, respectively. These doses resulted in median tumor-to-kidney dose ratios of 11.6 (IQR: 8.11–14.4) without SG and 13.0 (IQR: 10.2–18.6) with SG; these values were not significantly different (P = 1.0). The median tumor-to-stomach dose ratio was 3.34 (IQR: 1.14–4.70). Adverse reactions (mainly hypotension, flushing, and hypokalemia) were self-limiting and not higher than grade 1. Conclusion: ¹⁷⁷Lu-PP-F11N accumulates specifically in MTC at a dose that is sufficient for a therapeutic approach. With a low kidney and bone marrow radiation dose, ¹⁷⁷Lu-PP-F11N shows a promising biodistribution. The dose-limiting organ is most likely the stomach. Further clinical studies are necessary to evaluate the maximum tolerated dose and the efficacy of ¹⁷⁷Lu-PP-F11N.