Rhenium-186-labeled hydroxyethylidene diphosphonate dosimetry and dosing guidelines for the palliation of skeletal metastases from androgen-independent prostate cancer.

Abstract

Rhenium-186 (tin)-labeled hydroxyethylidene diphosphonate (186Re-labeled HEDP) was evaluated in 27 men with progressive androgen-independent prostate cancer and bone metastases. Administered activities ranged from 1251 to 4336 MBq (33.8-117.2 mCi). The primary objectives were to assess tumor targeting, normal organ dosimetry, and safety. Antitumor effects were assessed by posttherapy changes in prostate-specific antigen and, when present, palliation of pain. Whole-body kinetics, blood and kidney clearance, skeletal dose, marrow dose, and urinary excretion of the isotope were assessed. Targeting of skeletal disease was observed over the period of quantification (4-168 h). Radiation doses to whole body, bladder, and kidney were well tolerated. The dose-limiting toxicity was myelosuppression (grade III) at 4107 MBq (111 mCi) and grade II at 296 MBq (80 mCi). Probe clearance (whole body) and urinary excretion measurements were highly correlated. Of the six patients treated at the highest dosage schedules (three at 1510 MBq/m2 and three at 1665 MBq/m2), three showed a posttherapy decline in prostate-specific antigen of 50% or more. The declines were not sustained. The determination of total activity retained at 24 h, as well as an estimate of marrow dose, correlated with the amount of myelosuppression observed. These results suggest that a single 24-h measurement of retained activity would allow individualized dosing and an improved therapeutic index relative to fixed dosing schema. Repetitive dosing is required to increase palliation.