Somatostatin Receptor Antagonists for Imaging and Therapy.
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TLDR
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.Abstract:
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.read more
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References
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Jean Claude Reubi,Jean-Claude Schär,Beatrice Waser,Sandra Wenger,A. Heppeler,Jörg S. Schmitt,Helmut R. Mäcke +6 more
TL;DR: In vivo somatostatin receptor scintigraphy using Octreoscan is a valuable method for the visualisation of human endocrine tumours and their metastases and small structural modifications, chelator substitution or metal replacement were shown to considerably affect the binding affinity.
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ENETS Consensus Guidelines Update for the Management of Distant Metastatic Disease of Intestinal, Pancreatic, Bronchial Neuroendocrine Neoplasms (NEN) and NEN of Unknown Primary Site
Marianne Pavel,Dermot O'Toole,Frederico Costa,Jaume Capdevila,David J. Gross,Reza Kianmanesh,Eric P. Krenning,Ulrich Knigge,Ramon Salazar,Ulrich-Frank Pape,Kjell Öberg +10 more
TL;DR: The goal of this paper is to update a more extensive review and guidelines paper published in 2012 with any pertinent update pertaining to the diagnosis and staging of individual prima prima cancer patients.
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Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors
Mihaela Ginj,Hanwen Zhang,Beatrice Waser,Renzo Cescato,Damian Wild,Xuejuan Wang,Judit Erchegyi,Jean Rivier,Helmut R. Mäcke,Jean Claude Reubi +9 more
TL;DR: Somatostatin antagonist radiotracers are preferable over agonists for the in vivo targeting of sst3- or sst2-expressing tumors, and antagonists for other peptide receptors need to be evaluated in nuclear oncology as a result of this paradigm shift.
Journal ArticleDOI
Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?
Patricia Antunes,Mihaela Ginj,Hanwen Zhang,B. Waser,Richard P. Baum,Jean Claude Reubi,Helmut R. Maecke +6 more
TL;DR: This study demonstrates that 67/68Ga-DOTA-octapeptides show distinctly better preclinical, pharmacological performances than the 111In-labelled peptides, especially on sst2-expressing cells and the corresponding animal models, and may be excellent candidates for further development for clinical studies.
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