ArticleProceedings of the National Academy of Sciences of the United States of America2006
Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 206 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
206 citing papers in PubMed, 1 synthesis or guideline pooled it, 494 citations in OpenAlex.
- Theranostic Radiopharmaceuticals of Somatostatin Receptors for Patients with Neuroendocrine Tumors: Agonists Versus Antagonists-A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2025Pooled it
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- A prospective randomized, double-blind study to evaluate the diagnostic efficacy ofEuropean journal of nuclear medicine and molecular imaging · 2022Trial
- A Randomized, Factorial Phase II Study to Determine the Optimal Dosing Regimen forJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022Trial
- A Prospective, Randomized, Double-Blind Study to Evaluate the Safety, Biodistribution, and Dosimetry ofJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2021Trial
- Comparison ofEuropean journal of nuclear medicine and molecular imaging · 2020Trial
- Biodistribution and radiation dose estimates forEuropean journal of nuclear medicine and molecular imaging · 2019Trial
- Evaluation of (68)Ga-DOTA-TOC PET/CT for the detection of duodenopancreatic neuroendocrine tumors in patients with MEN1.European journal of nuclear medicine and molecular imaging · 2016Trial
- Positron emission tomography (PET) imaging of prostate cancer with a gastrin releasing peptide receptor antagonist--from mice to men.Theranostics · 2014Trial
- Development of dual SSTRSC medicinal chemistry · 2026Article
- Head-to-head comparison of [European journal of nuclear medicine and molecular imaging · 2026Article
- Radiolabelled somatostatin receptor antagonist versus agonist for peptide receptor radionuclide therapy in patients with metastatic pheochromocytoma or paraganglioma: a retrospective pilot study.European journal of nuclear medicine and molecular imaging · 2026Article
- From DNA-Encoded Chemistry to Tumor-Targeted Small Molecule Therapeutics.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Increased progression free survival with radiolabelled somatostatin receptor antagonist versus standard peptide receptor radionuclide therapy in patients with somatostatin receptor positive tumours.European journal of nuclear medicine and molecular imaging · 2026Article
- Controversies in NEN: An ENETS position statement on the interchangeability of somatostatin receptor PET tracers.Journal of neuroendocrinology · 2026Review
- Radionuclide‑drug conjugates in lung cancer: advances in precision therapy and clinical translation.Molecular cancer · 2026Review
- Peptide receptor radionuclide therapy in neuroendocrine tumours: advances, combination strategies, and future directions.European journal of nuclear medicine and molecular imaging · 2026Review
- Somatostatin and Its Analogues as Second-Line Treatments in Non-Neoplastic Conditions.International journal of molecular sciences · 2026Review
- Medical Management of Well-Differentiated Pancreatic Neuroendocrine Tumors: From Conventional Therapies to Emerging Strategies.Journal of clinical medicine · 2026Review
146 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Targeting neuroendocrine tumors expressing somatostatin receptor subtypes (sst) with radiolabeled somatostatin agonists is an established diagnostic and therapeutic approach in oncology. While agonists readily internalize into tumor cells, permitting accumulation of radioactivity, radiolabeled antagonists do not, and they have not been considered for tumor targeting. The macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was coupled to two potent somatostatin receptor-selective peptide antagonists [NH(2)-CO-c(DCys-Phe-Tyr-DAgl(8)(Me,2-naphthoyl)-Lys-Thr-Phe-Cys)-OH (sst(3)-ODN-8) and a sst(2)-selective antagonist (sst(2)-ANT)], for labeling with (111/nat)In. (111/nat)In-DOTA-sst(3)-ODN-8 and (111/nat)In-DOTA-[4-NO(2)-Phe-c(DCys-Tyr-DTrp-Lys-Thr-Cys)-DTyr-NH(2)] ((111/nat)In-DOTA-sst(2)-ANT) showed high sst(3)- and sst(2)-binding affinity, respectively. They did not trigger sst(3) or sst(2) internalization but prevented agonist-stimulated internalization. (111)In-DOTA-sst(3)-ODN-8 and (111)In-DOTA-sst(2)-ANT were injected intravenously into mice bearing sst(3)- and sst(2)-expressing tumors, and their biodistribution was monitored. In the sst(3)-expressing tumors, strong accumulation of (111)In-DOTA-sst(3)-ODN-8 was observed, peaking at 1 h with 60% injected radioactivity per gram of tissue and remaining at a high level for >72 h. Excess of sst(3)-ODN-8 blocked uptake. As a control, the potent agonist (111)In-DOTA-[1-Nal(3)]-octreotide, with strong sst(3)-binding and internalization properties showed a much lower and shorter-lasting uptake in sst(3)-expressing tumors. Similarly, (111)In-DOTA-sst(2)-ANT was injected into mice bearing sst(2)-expressing tumors. Tumor uptake was considerably higher than with the highly potent sst(2)-selective agonist (111)In-diethylenetriaminepentaacetic acid-[Tyr(3),Thr(8)]-octreotide ((111)In-DTPA-TATE). Scatchard plots showed that antagonists labeled many more sites than agonists. Somatostatin antagonist radiotracers therefore are preferable over agonists for the in vivo targeting of sst(3)- or sst(2)-expressing tumors. Antagonist radioligands for other peptide receptors need to be evaluated in nuclear oncology as a result of this paradigm shift.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.