ECE2024 Oral Communications Oral Communications 7: Endocrine-related Cancer (6 abstracts)
How close we are to optimise the assessment of SSTR status in NEN with a radiolabelled SSTR antagonist-final results of the TECANT clinical trial: Novel 99mTc-labelled somatostatin antagonists in the diagnostic algorithm of neuroendocrine neoplasms
Alicja Hubalewska-Dydejczyk 1 , Luka Ležaić 2 , Clemens Decristoforo 3 , Renata Mikolajczak 4 , Irene Virgolini 3 , Petra Kolenc 2 , Andrej Suden 5 , Urban Simoncic 5 , Marta Opalinska , Malgorzata Trofimiuk-Muldner , Piotr Garnuszek 4 , Gianpaolo di Santo 3 , Doroteja Novak 2 , Christine Rangger 3 , Marko Kroselj 2 , Konrad Skorkiewicz 6 , Melpomeni Fani 7 , Barbara Janota 4 , Boguslaw Glowa 6 & Agnieszka Sawicka 4
1Jagiellonian University Medical College, Department of Endocrinology, Kraków, Poland; 2University Medical Centre Ljubljana, Department of Nuclear Medicine, Ljubljana, Slovenia; 3Medical University Innsbruck, Department of Nuclear Medicine,, Innsbruck, Austria; 4National Centre For Nuclear Research Radioisotope Centre POLATOM, National Centre For Nuclear Research Radioisotope Centre POLATOM, Otwock, Poland; 5University of Ljubljana, Faculty of Mathematics and Physics, Ljubljana, Slovenia; 6SP ZOZ Szpital Uniwersytecki w Krakowie, Kraków, Poland; 7Universitätsspital Basel, Basel, Switzerland
Introduction/Aim: Within the past two decades, the imaging and treatment of patients with neuroendocrine neoplasms (NEN) has been redefined by the successful introduction of radiolabelled somatostatin receptor (SSTR)-agonists targeting SSTR-subtype2 (SSTR2) overexpressed in NEN cells. Reliable assessment of the SSTR status of the primary focus/metastasis in different NEN locations is a cornerstone of NEN management and enables a personalised/precise therapeutic approach. Recently, novel molecular probes based on antagonists have been shown to recognise more binding sites compared to commonly used agonists, which should lead to improved diagnostic/treatment outcomes for NEN patients, especially at lower SSTR expression. The aim of the multicenter phase 0/1 TECANT study was to develop a99m Tc-labelled SSTR2-antagonist, a new sensitive diagnostic tool for a reliable SSTR status assessment on tumour cells and to initiate a clinical feasibility study.
Material/Methods: Within the preclinical study, two radiolabelled SSTR2-antagonists: N4-LM-3(TECANT1) and N4-p-Cl-BASS(TECANT2), were tested in cell lines and animal studies assessing receptor affinity, internalisation status, toxicity, biodistribution and SSTR targeting properties. [99m Tc]Tc-TECANT1 showed better targeting properties/lower toxicity, and was ultimately selected for clinical trial. Ten patients with advanced NEN and SSTR-positivity confirmed by routinely performed [68 Ga]Ga-DOTA-TATE/TOC-PET/CT were enrolled in clinical study (EudraCT no:2019-003379-20). Safety, tolerability, human pharmacokinetics, dosimetry, and NEN targeting properties of the TECANT1 were assessed. Clinical and imaging data collected at each clinical center were stored in a centralized secured database to standardize image analysis and integrate statistical tools.
Results: [99m Tc]Tc-TECANT1 SPECT/CT was performed in all patients and no radiopharmaceutical-related side effects were observed. Tumour uptake was visible as early as 5 minutes after administration and retained 24 hours p.i. In all patients, rapid distribution with predominant renal excretion with a typical pattern for SSTR-analogues was observed. An excellent visualization of NEN lesions was obtained; in most cases with tumour-to-background ratio(TBR) superior to 68 Ga-SSTR-agonists, with the highest values of TBR at 4 hours p.i.
Conclusions: Images obtained with [99m Tc]Tc-TECANT1 appear to be of great clinical importance and may be a step toward a more reliable assessment of SSTR status. Detailed quantitative analysis will be reported to support the initial highly comparable diagnostic performance to [68 Ga] Ga-DOTA-TATE PET/CT. Using a99m Tc-labeled SSTR antagonist may provide a widely available method for SPECT imaging, which should lead to further improvements in personalised NEN management.
This research is a part of the project “Novel99m Tc-labelled somatostatin receptor antagonists in the diagnostic algorithm of neuroendocrine neoplasms-a feasibility study” (TECANT), funded by ERA PerMed (ERAPERMED2018-125).
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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