Prediction of human PET imaging dose to monitor NHL therapy using <64>Cu-DOTA-rituximab and a transgenic mouse model

Objectives In this study we attempted to predict human dosimetry for a novel antibody based PET tracer, <64>Cu-DOTA-rituximab prior to clinical translation.

Methods To validate the PET tracer multiple radiolabeling, Quality assurance (QA), and imaging experiments were carried out in three groups of transgenic mice (CD20TM) that express the human CD20 on their B cells. The study groups of mice are as follows; a) control (nude mice, n=2) that received 7.4 MBq <64>Cu-rituximab, b) with pre-dose (CD20TM, n=6): received 2 mg/kg pre-dose of cold rituximab prior to 7.4 MBq <64>Cu-DOTA-rituximab, and c) without pre-dose (CD20TM, n=6) 7.4 MBq <64>Cu-DOTA-rituximab. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72 h) post-injection of <64>Cu-DOTA-rituximab. Organs were delineated on small animal PET and computed tomography (CT) images. The OLINDA/EXM application was used to determine the human equivalent dose for individual organs.

Results QA of tracer showed specific activity of 545 ± 38.91 TBq/mol, RCY >80%, IR >80% and purity >95%. At 24 h, spleen uptake of PET tracer in %ID/g (mean ± STD) was 1.76 ± 0.43 and 16.5 ± 0.45 with and without pre-dosing, respectively (P < 0.011); liver uptake was 0.41 ± 0.51 and 0.52 ± 0.17 with and without pre-dosing, respectively. The spleen specific uptake of PET tracer is approximately 15 times higher than the liver due to the expression of huCD20. The human equivalent of the highest dosed organ is osteogenic cells 42.2 ± 0.002 mSv/MBq.

Conclusions Pre-clinical evaluation of <64>Cu-rituximab with huCD20TM showed that this novel PET tracer is able to specifically image huCD20. Human dosimetry of PET tracer was estimated for clinical translation and an IND has been obtained (IND #104995).

Research Support ICMIC P50 - CA11474