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

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

Volume: 9 Issue: 1

Author(s): Chandrasekhar Bal, Geetanjali Arora, Praveen Kumar, Nishikant Damle, Tapas Das, Sudipta Chakraborty, Sharmila Banerjee, Meera Venkatesh, John J. Zaknun and M. R.A. Pillai

Affiliation:

Keywords: ¹⁷⁷Lu-EDTMP, bone pain palliation, dosimetry, maximum tolerated dose, phase 0/I study, toxicity.

Abstract: 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.

Cite this article as:

Bal Chandrasekhar, Arora Geetanjali, Kumar Praveen, Damle Nishikant, Das Tapas, Chakraborty Sudipta, Banerjee Sharmila, Venkatesh Meera, Zaknun J. John and Pillai R.A. M., Pharmacokinetic, Dosimetry and Toxicity Study of ¹⁷⁷Lu-EDTMP in Patients: Phase 0/I study, Current Radiopharmaceuticals 2016; 9 (1) . https://dx.doi.org/10.2174/1874471008666150313105000