Pharmacokinetic, Dosimetry and Toxicity Study of ;177Lu-EDTMP in Patients: Phase 0/I study

177 has been proposed as a potent bone pain palliation agent owing to theoretical advantage of reduced bone marrow suppression resulting from the low β-& energy and a suitably long half-life facilitating its wider distribution with less loss from radioactive decay. Herein, we report the pharmacokinetics, dosimetry and toxicity analysis of 177 in patients (phase-0/I study). In a phase-0 study, the biokinetics of skeletal and non-skeletal uptake of 177 was assessed in 6 patients with metastatic prostate cancer using tracer doses (172.7–206.9MBq). Data of whole skeletal uptake, blood and fractionated urine samples were obtained and dosimetric calculations were performed using the OLINDA/EXM 1.0 software. Prolonged bone retention was observed in all patients. Excretion was mainly via the renal route and blood clearance was rapid and biphasic. Mean estimated red marrow dose was 0.80±0.15mGy/MBq while mean total-body dose was 0.16±0.04mGy/MBq. A maximum tolerated dose (MTD) of 2000-3250MBqfor 177 was calculated. For the phase-I study, 21 patients with metastatic prostate cancer were given a therapeutic dose of 177 EDTMP (692-5550MBq). Toxiciy (WHO), evaluated by assessment of hemoglobin levels, platelet and leukocyte counts over 12 weeks, was mainly limited to anemia or thrombocytopenia. Only transient toxicity was observed in 14/21 patients, of which 6 had baseline toxicity. Beyond the MTD, a significantly higher number of patients displayed grade 3-4 toxicity. Pain relief, assessed by VAS pain score, was observed in 86% patients with median relief duration of 7 weeks. The results demonstrate that 177 has excellent pharmacokinetic and dosimetric properties, besides being safe and effective. Along with estimating radiation dose values to certain critical organs, we have also proposed an MTD for 177 that correlated well with toxicity data. The encouraging dosimetry and toxicity data of 177 reported provide the basis for subsequent phases of the studies to establish complete effectiveness and safety of 177 as an attractive alternative to other radioactive bone pain palliation agents.