Prediction of Myelotoxicity Based on Bone Marrow Radiation-Absorbed Dose: Radioimmunotherapy Studies Using 90Y- and 177Lu-Labeled J591 Antibodies Specific for Prostate-Specific Membrane Antigen

In radioimmunotherapy, myelotoxicity due to bone marrow ra-diation-absorbed dose is the predominant factor and frequently is the dose-limiting factor that determines the maximum toler-ated dose (MTD). With 90Y- and 131I-labeled monoclonal anti-bodies, it has been reported that myelotoxicity cannot be pre-dicted on the basis of the amount of radioactive dose administered or the bone marrow radiation-absorbed dose (BMrad), estimated using blood radioactivity concentration. As part of a phase I dose-escalation study in patients with prostate cancer with 90Y-DOTA-J591 (DOTA 1,4,7,10-tetraazacy-clododecane-N,N,N,N-tetraacetic acid) (90Y-J591) and 177Lu-DOTA-J591 (177Lu-J591), we evaluated the potential value of several factors in predicting myelotoxicity. Methods: Seven groups of patients (n 28) received 370–2,775 MBq/m2 (10–75 mCi/m2) of 177Lu-J591 and 5 groups of patients (n 27) re