Radiation Dosimetry Study of [(89)Zr]rituximab Tracer for Clinical Translation of B cell NHL Imaging using Positron Emission Tomography.

ABSTRACT: We evaluated the dosimetry of [(89)Zr]rituximab, an anti-CD20 immunoPET tracer to image B cell non-Hodgkin's lymphoma (NHL) using a humanized transgenic mouse model that expresses human CD20 transgenic mice (huCD20TM).Rituximab was conjugated to desferrioxamine (Df) for radiolabeling of Zirconium-89. [(89)Zr]rituximab (2.8?±?0.2 MBq) was tail vein-injected into huCD20T mice. Positron emission tomography (PET)/CT imaging was performed on the two groups of mice (blocking?=?2 mg/kg pre-dose of rituximab and non-blocking; n?=?5) at eight time points (1, 4, 24, 48, 72, 96, 120, and 168 h) post injection.The novel [(89)Zr]rituximab PET tracer had good immunoreactivity, was stable in human serum, and was able to specifically target human CD20 in mice. The human equivalents of highest dose (mean?±?SD) organs with and without pre-dose are liver (345?±?284 ?Sv/MBq) and spleen (1165?±?149 ?Sv/MBq), respectively.Dosimetry of the human patient whole-body dose was found to be 145 MBq per annum, and the patient dose-limiting organ will be the liver (with rituximab pre-dose blocking) and spleen for non-blocking. The [(89)Zr]rituximab (t½?=?78.4 h) imaging of B cell NHL patients could permit the observation of targeting lesions in NHL patients over an extended period due to longer half-life as compared to the [(64)Cu] rituximab (t½?=?12.7 h).

SUBMITTER: Natarajan A 

PROVIDER: S-EPMC4465424 | biostudies-other | 2015 Aug

REPOSITORIES: biostudies-other