Positron Emission Tomography of 64Cu-DOTA-Rituximab in a Transgenic Mouse Model Expressing Human CD20 for Clinical Translation to Image NHL

This study aims to evaluate Cu-64-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation. Cu-64 was chelated to DOTA-rituximab. Multiple radiolabeling, quality assurance, and imaging experiments were performed. The human CD20 antigen was expressed in B cells of transgenic mice (CD20TM). The mice groups studied were: (a) control (nude mice, n = 3) that received 7.4 MBq/dose, (b) with pre-dose (CD20TM, n = 6) received 2 mg/kg pre-dose of cold rituximab prior to PETRIT of 7.4 MBq/dose, and (c) without pre-dose (CD20TM, n = 6) PETRIT alone received 7.4 MBq/dose. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72 h). The OLINDA/EXM software was used to determine the human equivalent dose for individual organs. PETRIT was obtained with a specific activity of 545 +/- 38.91 MBq/nmole, radiochemical purity > 95%, and immunoreactivity > 75%. At 24 h, spleenic uptake of PETRIT%ID/g (mean +/- STD) with and without pre-dose was 1.76 +/- 0.43% and 16.5 +/- 0.45%, respectively (P value = 0.01). Liver uptake with and without pre-dose was 0.41 +/- 0.51% and 0.52 +/- 0.17% (P value = 0.86), respectively. The human equivalents of highest dose organs with and without pre-dose are osteogenic cells at 30.8 +/- 0.4 mu Sv/MBq and the spleen at 99 +/- 4 mu Sv/MBq, respectively. PET imaging with PETRIT in huCD20 transgenic mice provided human dosimetry data for eventual applications in non-Hodgkins lymphoma patients.