Biodistribution and Radiation Dosimetry for 68Ga-DOTA-CCK-66, a Novel CCK2R-Targeting Compound for Imaging of Medullary Thyroid Cancer

Abstract

Abstract Cholecystokinin 2 receptor (CCK2R) is a promising target for imaging and treatment of medullary thyroid cancer due to its overexpression in over 90% of tumor cells. 68Ga-DOTA-CCK-66 is a recently introduced PET tracer selective for CCK2R, which has shown favorable pharmacokinetics in vivo in preclinical experiments. In order to further investigate safety and suitability of this tracer in the human setting, whole-body distribution and radiation dosimetry were evaluated. Patients and Methods Six patients with a history of medullary thyroid cancer were injected intravenously with 169 ± 19 MBq of 68Ga-DOTA-CCK-66. Whole-body PET/CT scans were acquired at 10 minutes, 1 hour, 2 hours, and 4 hours after tracer injection. Time-activity curves per organ were determined, and mean organ-absorbed doses and effective doses were calculated using OLINDA/EXM. Results Injection of a standard activity of 150 MBq of 68Ga-DOTA-CCK-66 results in an effective dose of 4.5 ± 0.9 mSv. The highest absorbed organ doses were observed in the urinary bladder wall (40 mGy) and the stomach (15 mGy), followed by the kidneys (6 mGy), as well as the liver and the spleen (3 mGy each). CCK2R-expressing tumor manifestations could be detected in 2 of the 6 patients, including lymph node, bone, and liver metastases. Conclusions 68Ga-DOTA-CCK-66 exhibits a favorable dosimetry. Beyond physiologic receptor expression of the stomach, no other relevant tracer accumulation could be observed, rendering this organ at risk in case of subsequent radioligand therapy using 177Lu-DOTA-CCK-66.