Somatostatin receptor antagonists for imaging and therapy.
Open accessAbstract
Somatostatin receptor (sstr) scintigraphy for imaging and sstr analogs for treatment have been used for more than 20 y. An important improvement in recent years was the introduction of peptide receptor radionuclide therapy with radiolabeled sstr agonists, such as [90Y-DOTA0,Tyr3]octreotide or [177Lu-DOTA0,Tyr3]octreotide (90Y- or 177Lu-DOTATOC, respectively) and [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE). PET/CT with 68Ga-labeled sstr agonists, such as 68Ga-DOTATOC, 68Ga-DOTATATE, and [68Ga-DOTA,1-Nal3]octreotide (68Ga-DOTANOC), plays an important role in staging and restaging neuroendocrine tumors. Most importantly, sstr scintigraphy and sstr PET/CT can distinguish patients who will qualify for and benefit from peptide receptor radionuclide therapy. This characteristic of sstr targeting is important because it allows a personalized treatment approach (theranostic approach). Until recently, it was thought that internalization of the radiolabeled agonist was mandatory for sstr-mediated imaging and therapy. It was Ginj et al. who proposed in 2006 the paradigm shift that radiolabeled sstr antagonists may perform better than agonists despite the lack of internalization. Despite the rather limited number of head-to-head comparisons of sstr antagonists and agonists, the superiority of sstr antagonists was demonstrated in several cases. From a small library of sstr antagonists, the analog JR11 (Cpa-c[d-Cys-Aph(Hor)-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2), an antagonist with selectivity for sstr subtype 2, showed the best overall characteristics for sstr subtype 2 targeting and was therefore selected for clinical translation. JR11 is under clinical development as a PET imaging agent when labeled with 68Ga (68Ga-NODAGA-JR11 or 68Ga-OPS202) and as a therapeutic agent when labeled with 177Lu (177Lu-DOTA-JR11 or 177Lu-OPS201). In this article, we discuss the development and current status of radiolabeled sstr antagonists. Evidence based on preclinical work, on quantitative in vivo autoradiography of human tumor slices, and on human data now supports a shift to sstr antagonists.
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Using radiolabeled SSTR antagonists, especially LM3 and JR11, may provide more successful imaging and PRRT strategies for neuroendocrine tumors, even those with relatively low SSTR expression, compared to agonists.
“Taking the proposed mechanism, preclinical and clinical studies into consideration, it is obvious that using radiolabeled SSTR antagonists, especially LM3 and JR11, may provide more successful imaging and PRRT strategies for neuroendocrine tumors, even those with relatively low SSTR expression (130, 137, 141) compared to agonists.”
From Alpha-peptide receptor radionuclide therapy using actinium-225 labeled somatostatin receptor agonists and antagonists (2022) · cites this paper as [141]
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- Authors
- Fani, M., Nicolas, G. P., & Wild, D.
- Affiliations
- University Hospital of Basel (CH)
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2017-09
- Volume
- 58
- Issue
- Supplement 2
- Pages
- 61S-66S
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- OpenAlex
- W2752482655
- Cited by
- 274
- References
- 24
- Citations by year
- 2026: 15 · 2025: 31 · 2024: 27 · 2023: 38 · 2022: 21 · 2021: 36 · 2020: 39 · 2019: 37 · 2018: 24 · 2017: 5 · 2014: 1
- FWCI
- 22.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- somatostatin receptor antagonists, somatostatin receptor scintigraphy, peptide receptor radionuclide therapy, neuroendocrine tumors, theranostics, 68Ga-DOTATOC, 177Lu-DOTATOC, receptor internalization, somatostatin receptor 2, radiolabeled somatostatin analogs
- MeSH terms
- Animals, Diagnostic Imaging, Humans, Isotope Labeling, Receptors, Somatostatin, Drug Discovery, Molecular Targeted Therapy
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