Cholecystokinin-2 Receptor Agonist 177Lu-PP-F11N for Radionuclide Therapy of Medullary Thyroid Carcinoma - Results of the Lumed Phase 0a Study.

Rottenburger, Christof; Nicolas, Guillaume P; McDougall, Lisa; Kaul, Felix; Cachovan, Michal; Vija, A Hans; Schibli, Roger; Geistlich, Susanne; Schumann, Anne; Rau, Tilman; Glatz, Kathrin; Behe, Martin; Christ, Emanuel R; Wild, Damian (2020). Cholecystokinin-2 Receptor Agonist 177Lu-PP-F11N for Radionuclide Therapy of Medullary Thyroid Carcinoma - Results of the Lumed Phase 0a Study. Journal of nuclear medicine, 61(4), pp. 520-526. Society of Nuclear Medicine 10.2967/jnumed.119.233031

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Treatment of patients with advanced medullary thyroid carcinoma (MTC) is still a challenge. For more than 2 decades it is known that cholecystokinine-2 receptor (CCK2R) is a promising target for the treatment of MTC with radiolabeled minigastrin analogues. Unfortunately, kidney toxicity precluded their therapeutic application so far. In 6 consecutive patients we evaluated with advanced 3D dosimetry whether improved minigastrin analogue 177Lu-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Nle-Asp-PheNH2 (177Lu-PP-F11N) is a suitable agent for the treatment of MTC. Methods: Patients received two injections of about 1 GBq (~80 µg) 177Lu-PP-F11N with and without a solution of succinylated gelatin (SG, a plasma expander used for nephroprotection) in a random cross-over sequence in order to evaluate biodistribution, pharmacokinetics as well as tumor- and organ dosimetry. ECG, blood count and blood chemistry were measured up to 12 weeks after administration of 177Lu-PP-F11N to assess safety. Results: In all patients 177Lu-PP-F11N accumulation was visible in tumor tissue, stomach and kidneys. Altogether 13 tumors were eligible for dosimetry. The median (interquartile range = IQR) absorbed dose for tumors, stomach, kidneys and bone marrow was 0.88 Gy/GBq (0.85-1.04), 0.42 (0.25-1.01), 0.11 (0.07-0.13) and 0.028 (0.026-0.034). These resulted in a median (IQR) tumor-to-kidney dose ratio of 11.6 (8.11-14.4) without SG and 13.0 (10.2-18.6) with SG, which were not significantly different (P = 1.0). The median (IQR) tumor-to-stomach dose ratio was 3.34 (1.14-4.7). Adverse reactions (mainly hypotension, flushing and hypokalemia) were self-limiting and not higher than grade 1. Conclusion:177Lu-PP-F11N accumulates specifically in MTC at a dose that is sufficient for a therapeutic approach. With little kidney and bone marrow radiation dose 177Lu-PP-F11N shows promising biodistribution. The dose limiting organ is most likely the stomach. Further clinical studies are necessary to evaluate the maximum tolerated dose and the efficacy of 177Lu-PP-F11N.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Rau, Tilman


500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health




Society of Nuclear Medicine




Tilman Rau

Date Deposited:

13 Jan 2020 09:25

Last Modified:

04 Apr 2020 01:32

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

<sup>177</sup>Lu-PP-FF11N Cholecystokinine-2 receptor targeting Oncology: Endocrine PRRT Radiation Therapy Planning Radionuclide Therapy Theranostics




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