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Endocrine Abstracts (2019) 63 GP226 | DOI: 10.1530/endoabs.63.GP226

ECE2019 Guided Posters Adrenal and Neuroendocrine - Clinical (1) (10 abstracts)

Evaluation of the CCK-2 receptor agonist 177Lu-PP-F11N for radionuclide therapy of medullary thyroid carcinoma – final Results of the phase 0 ‘Lumed’ Study

Christof Rottenburger 1 , Guillaume Nicolas 1 , Lisa McDougall 1 , Felix Kaul 1 , Michael Cachovan 2 , Roger Schibli 3 , Susanne Geistlich 3 , Martin Béhé 3 , Damian Wild 1 & Emanuel Christ 4


1Division of Nuclear Medicine, University Hospital of Basel, Basel, Switzerland; 2Siemens healthcare GmbH, Forcheim, Germany; 3Center for Radiopharmaceutical Sciences, Paul Scherrer, Villigen, Switzerland; 4Division of Endocrinology, Diabetology and Metabolism, Basel, Switzerland.

Objectives: 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 clinical study is to test the proof of principle that the novel gastrin analogue [177Lu-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Nleu-Asp-PheNH2] (177Lu-PP-F11N) targets effectively metastases of MTC ( NCT02088645).

Methods: Six patients received two injections of 1 GBq 177Lu-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 tumor- and organ doses using 3D volume based MIRD 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 177Lu-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, 177Lu-PP-F11N accumulation was visible in tumor tissue, in the kidneys, stomach and the colon. Altogether, 13 tumors were eligible for dosimetry. The median (range) radiation dose for tumors, stomach, kidneys and bone marrow was 0.88 Gy/GBq (0.38–8.04), 0.42 (0.13–2.07), 0.1 (0.05–0.15) and 0.010 (0.008–0.016). These resulted in median tumor-to-kidney dose ratios of 12.3 (6.8–27.6) (without Physiogel) and 13.0 (6.4–21.8) (with Physiogel), which was not significantly different (Wilcoxon test P=0.19). The median tumor-to-bone marrow dose ratio was 77.7 (52.8–398.5).

Conclusions: The administration of the novel CCK-2 receptor ligand 177Lu-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 177Lu-PP-F11N is feasible in patients with MTC. The dosimetry results indicate tumor doses that could enable radionuclide therapy. Dosimetry results for kidneys and bone marrow revealed low organ doses, as well as excellent tumor-to-kidney and tumor-to-bone marrow ratios. Further studies will be necessary to evaluate the theranostic potential of 177Lu-PP-F11N in patients with CCK-2 receptor expressing tumors.

Volume 63

21st European Congress of Endocrinology

Lyon, France
18 May 2019 - 21 May 2019

European Society of Endocrinology 

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