Endocrine Abstracts

Objectives: There is still an unmet need for an effective systemic therapy for advanced medullary thyroid carcinoma (MTC). Targeting the cholecystokinine-2 (CCK-2) receptor with radiolabelled gastrin analogues is a potential approach for radionuclide therapy, as MTC expresses CCK-2 receptors at a high incidence and density. Unfortunately, kidney and bone marrow toxicity precluded therapeutic applications of CCK-2 receptor specific compounds until now. The aim of this prospective study is the feasibility testing of targeting CCK-2 receptors with the novel 177Lu labelled gastrin analogue PP-F11N [DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Nleu-Asp-PheNH2]in six patients with metastasized MTC (ClinicalTrials.gov: NCT02088645).

Methods: Six patients received two injections of 1 GBq 177Lu-PP-F11N, one injection without and the other one with additional Physiogel infusion for nephroprotection. 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 voxel-based dosimetry. Blood samples were taken for the purpose of bone marrow dose calculation. 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: Apart from self-limiting flushing, nausea and vomiting (grade 1 according to CTCAE version 4.0), there were no adverse reactions observed. In all patients, radiotracer uptake in tumor tissue was visible in the scintigraphic images. Furthermore, uptake in the kidneys, stomach and colon was visible. The radiation doses to the tumors and organs were calculated for the three patients: dose range in tumors was between 1 and 1.5 Gy/GBq, dose range in kidneys 0.045–0.075 Gy/GBq (without Physiogel) and 0.07–0.15 Gy/GBq (with Physiogel), resulting in tumor-to-kidney dose ratios between 13.3 and 27.3. Calculated bone marrow doses were 0.01–0.02 Gy/GBq, resulting in tumor-to-bone marrow dose ratios between 50 and 150.

Conclusions: The administration of the new CCK-2 receptor ligand 177Lu-PP-F11N was safe. Visualization of metastasized/recurrent disease in all patients proves that the principle of CCK-2 receptor targeting of MTC with this new radiopharmaceutical is feasible. Preliminary results of the 3D voxel-based dosimetry in the first three analyzed patients indicated 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 MTC.