ECE2023 Poster Presentations Endocrine-related Cancer (62 abstracts)
Management of NENs with SSTR2-antagonist: how close are we to a clinical solution? The first results of the TECANT study: Novel 99m-Tc-labelled somatostatin antagonists in the diagnostic algorithm of neuroendocrine neoplasms – a feasibility study
Alicja Hubalewska-Dydejczyk 1 , Clemens Decristoforo 2 , Petra Kolenc 3 , Renata Mikolajczak 4 , Luka Ležaić 3 , Andrej Suden 5 , Piotr Garnuszek 4 , Urban Simoncic 5 , Irene Virgolini 2 , Malgorzata Trofimiuk-Muldner 1 , Marta Opalinska 6 , Christine Rangger 2 , Boguslaw Glowa 7 , Konrad Skorkiewicz 7 , Melpomeni Fani 8 , Anna Sowa Staszczak 1 , Barbara Janota 4 , Marko Kroselj 3 , Katja Zaletel 3 & Elisabeth Von Guggenberg 2
1Jagiellonian University, Chair and Department of Endocrinology, Cracow, Poland; 2Medizinische Universität Innsbruck, Innsbruck, Austria; 3University Medical Centre Ljubljana, Ljubljana, Slovenia; 4National Centre for Nuclear Research Radioisotope Centre POLATOM, Otwock-Swierk, Poland; 5University of Ljubljana, Ljubljana, Slovenia; 1Jagiellonian University, Chair and Department of Endocrinology, Cracow, Poland; 7SP ZOZ Szpital Uniwersytecki w Krakowie, Kraków, Poland; 8Universitätsspital Basel, Basel, Switzerland
Introduction: The management of patients with neuroendocrine neoplasms (NEN) has been revolutionised since the introduction of radiolabelled somatostatin analogues targeting overexpressed somatostatin receptors (SSTR). Accurate assessment of SSTR status of primary focus/metastases is crucial to determine the choice of the treatment method. Recently it has been shown that novel molecular probes, SST2-antagonists, recognize more binding sites in comparison to the widely used SSTR2-agonists and hence improve diagnostic efficacy, especially when the density of SSTR is low. The aim of the project is to develop a novel 99mTc-labelled SSTR2-antagonist as a sensitive probe to assess the SSTR status in NEN patients.
Material and Methods: In frame of the first, extensive preclinical studies the most promising SSTR antagonist N4-LM-3 (p-Cl-Phe-cyclo(D-Cys-Tyr-DAph(Cbm)-Lys-Thr-Cys)-D-Tyr-NH2 (TECANT-1) was selected for clinical translation to initiate a clinical feasibility study including the development of a robust, reproducible quantitative imaging method of SSTR assessment in NEN tissues1. The clinical study is a phase I multicentre trial. Ten patients with advanced NEN and SSTR positivity confirmed by routinely used SSTR imaging based on a radiolabelled agonist will be enrolled in the study. Safety, tolerability, human pharmacology, dosimetry and NEN targeting properties of the compound tested will be assessed. Comparability of clinical and imaging data collected at imaging centres will be ensured through an established, centralized secured database also providing standardized image analysis protocols and integrated statistical tools.
Results: Within the TECANT project, the preselected 99mTc-labelled SSTR2-antagonist TECANT-1 was successfully developed into a kit formulation amenable for use in a hospital radiopharmacy setting. Together with the favourable toxicological and promising pharmacological profile, [99mTc]Tc-TECANT-1 is ready to be advanced into first-in-human multicentre clinical trial (EudraCT no: 2019-003379-20). After receiving positive opinion from the national authorities, the clinical part of the study has been initiated. No clinical side effects were observed after the first [99mTc]Tc-TECANT-1 application; a very good visualization of NEN metastases was obtained.
Conclusions: The first obtained images with radiolabelled SSTR2-antagonist appear to be of great clinical significance. The 99mTc-labelled SSTR2-antagonist is expected to enable a reliable and widely available method for quantitative assessment of SSTR status and to improve the decision-making diagnostic and therapeutic algorithm as one of the key elements in a personalised approach to the management of NEN patients.
Reference: Funding: ERAPerMed, FWF Austria, NCBiR Poland, MIZS Slovenia
1Melpomeni et al: Selection of the First 99mTc-Labelled Somatostatin Receptor Subtype 2 Antagonist for Clinical Translation-Preclinical Assessment of Two Optimized Candidates. Pharmaceuticals 2020;14(1):19;doi:10.3390/ph14010019
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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