177Lu-EDTMP 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 177Lu-EDTMP in patients (phase-0/I study). In a
phase-0 study, the biokinetics of skeletal and non-skeletal uptake of 177Lu-EDTMP 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 177Lu-EDTMP was
calculated. For the phase-I study, 21 patients with metastatic prostate cancer were given a therapeutic dose of 177Lu-
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 177Lu-EDTMP 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 177Lu-EDTMP
that correlated well with toxicity data. The encouraging dosimetry and toxicity data of 177Lu-EDTMP reported provide the
basis for subsequent phases of the studies to establish complete effectiveness and safety of 177Lu-EDTMP as an attractive
alternative to other radioactive bone pain palliation agents.