Kinetics and dosimetry of ¹²⁴I-PGN650, a PET tracer for phosphatidylserine exposure in solid tumors.

Objectives PGN650 is an F(ab’)₂ antibody fragment that targets phosphatidylserine (PS), which becomes exposed in the tumor microenvironment. PGN650 was labeled with ¹²⁴I for use with PET as an in vivo biomarker of PS exposure. In this phase 0 study, we evaluated its pharmacokinetics, radiation dosimetry and tumor uptake in a cohort of human patients.

Methods Eight patients with known advanced solid tumors (4 gastrointestinal cancer, 1 Ewing sarcoma, 1 melanoma, 2 lung cancer) received ~140 MBq of ¹²⁴I-PGN650 and underwent PET/CT at ~1 h, ~4 h and either 24 h or 48 h. Radiation dosimetry estimates were obtained from integration of the organ time-activity data and OLINDA for the adult male model. Radiation dosimetry was performed for individual patient and by combining data from all patients. In order to assess the safety of ¹²⁴I-PGN650, all patients underwent vital sign measurement, clinical laboratory testing, and ECG testing before, during and after completion of imaging. In addition, the patients were monitored for any side effect related to the drug for 7 d after injection. Tumor uptake was assessed qualitatively.

Results Activity was retained predominantly in the liver, spleen and blood; blood clearance was relatively slow (half-life of 46 h). Individual patient dosimetry indicated a dose of 1.35 mGy/MBq to the heart, kidneys and liver for an effective dose of 0.5 mSv/MBq. A bias was observed for patients imaged up to 24 h versus those imaged up to 48 h due to the clearance assumptions. Cumulative dosimetry indicated dose to kidneys, heart and liver of 0.81 mGy/MBq and an effective dose of 0.34 mSv/MBq. Increased tumor uptake was noted in 6 patients, and was best seen at 24 to 48 h. There were no adverse effects in any of the 8 patients, nor were there significant changes in vital signs, laboratory studies or ECGs.

Conclusions ¹²⁴I-PGN650 is safe and results in acceptable dosimetry and needs further optimization as an imaging agent based on the level of increased tumor uptake on PET/CT.

Research Support This work was performed with funds provided by Peregrine Pharmaceuticals Inc.