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

TY - JOUR

T1 - Positron Emission Tomography of (64)Cu-DOTA-Rituximab in a Transgenic Mouse Model Expressing Human CD20 for Clinical Translation to Image NHL

AU - Natarajan, Arutselvan

AU - Gowrishankar, Gayatri

AU - Nielsen, Carsten Haagen

AU - Wang, Sen

AU - Iagaru, Andrei

AU - Goris, Michael L

AU - Gambhir, Sanjiv Sam

PY - 2012/10

Y1 - 2012/10

N2 - PURPOSE: This study aims to evaluate (64)Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation. PROCEDURES: (64)Cu 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. RESULTS: 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 µSv/MBq and the spleen at 99¿±¿4 µSv/MBq, respectively. CONCLUSIONS: PET imaging with PETRIT in huCD20 transgenic mice provided human dosimetry data for eventual applications in non-Hodgkins lymphoma patients.

AB - PURPOSE: This study aims to evaluate (64)Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation. PROCEDURES: (64)Cu 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. RESULTS: 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 µSv/MBq and the spleen at 99¿±¿4 µSv/MBq, respectively. CONCLUSIONS: PET imaging with PETRIT in huCD20 transgenic mice provided human dosimetry data for eventual applications in non-Hodgkins lymphoma patients.

U2 - 10.1007/s11307-011-0537-8

DO - 10.1007/s11307-011-0537-8

M3 - Journal article

C2 - 22231277

SN - 1536-1632

VL - 14

SP - 608

EP - 616

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

IS - 5

ER -