SUN-334 Evaluation of the CCK-2 Receptor Agonist 177Lu-PP-F11N for PRRT of Medullary Thyroid Carcinoma: Results of a Phase 0 "Lumed" Study

• Published in: Journal of the Endocrine Society 2019-04, Vol.3 (Supplement_1)
• Main Authors: Rottenburger, Christof, Nicolas, Guillaume, McDougall, Lisa, Kaul, Felix, Cachovan, Michal, Schibli, Roger, Geistlich, Susanne, Behe, Martin, Wild, Damian, Christ, Emanuel
• Format: Article
• Language: English
• Subjects: Tumor Biology
• ISSN: 2472-1972; 2472-1972
• DOI: 10.1210/js.2019-SUN-334

Introduction: Despite the introduction of new molecular targeted therapies, there is still an unmet need for an effective systemic therapy for advanced medullary thyroid carcinoma (MTC). As MTC expresses cholecystokinine-2 (CCK-2) receptors at a high incidence and density, targeting the CCK-2 receptor with radiolabelled gastrin analogues is a potential approach for radionuclide therapy. Unfortunately, kidney and bone marrow toxicity precluded therapeutic applications of CCK-2 receptor specific radiotracers until now. The aim of this prospective study is the feasibility testing of targeting CCK-2 receptors with the novel gastrin analogue [ 177 Lu-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Nleu-Asp-PheNH2] ( 177 Lu-PP-F11N) in six patients with advanced MTC (ClinicalTrials.gov: NCT02088645). Subjects and Methods: Six patients received two injections of 1 GBq 177 Lu-PP-F11N, one injection with and the other without Physiogel (Gelofusin = plasma expander for nephroprotection) infusion. Planar scintigraphy and SPECT/CT scans were performed at several time points for up to 72 h post injection in order to calculate tumour- and organ doses using 3D voxel- and MIRD based dosimetry (Dosimetry Research Tool v5.2, Siemens Medical Solutions, USA). Blood samples were taken for bone marrow dose calculations. ECG, blood count and blood chemistry were measured up to 12 weeks after the second administration of 177 Lu-PP-F11N in order to evaluate adverse events. Results: Adverse reactions (mainly hypotension, flushing and hypokalemia) were self-limiting and not higher than grade 1, according to CTCAE version 4.03. In all patients, 177 Lu-PP-F11N accumulation was visible in tumor tissue, in the kidneys, stomach and the colon. Altogether, 14 tumours were eligible for dosimetry. The median (range) radiation dose for tumours, kidneys and bone marrow was 0.88 Gy/GBq (0.69-2.85), 0.090 (0.045-0.115) and 0.010 (0.008-0.016). These resulted in median tumour-to-kidney dose ratios of 12.8 (6.0-52.4) (without Physiogel) and 12.4 (6.4-29.8) (with Physiogel), which was not significantly different. The median tumour-to-bone marrow dose ratio was 87.9 (52.8-316.4). Discussion/Conclusion: The administration of the novel CCK-2 receptor ligand 177 Lu-PP-F11N was safe in all six examined patients. Visualization of metastasized/recurrent disease in all patients provides evidence that CCK-2 receptor targeting with 177 Lu-PP-F11N is feasible in patients with MTC. The dosimetry results indicate tumour doses tha