Preclinical positron emission tomography imaging properties of radiolabeled nimotuzumab : a retrospective analysis towards imaging application for visualizing epidermal growth factor receptor expression

Abstract

The purpose of this study was to evaluate the preclinical imaging properties of radiolabeled nimotuzumab (h-R3) for visualizing epidermal growth factor receptor (EGFR) expression using positron emission tomography (PET). The primary aim was to enhance knowledge of radiolabeled h-R3 to provide insight into its in vivo pharmacology and particular EGFR expression patterns using small animal PET imaging. The research involved a retrospective, exploratory analysis of data sets from animal studies conducted at Sir Charles Gairdner Hospital. This entailed analyzing data obtained from the injection of [89Zr]Zr-DFO-h-R3, [64Cu]Cu-DOTA-h-R3, and [64Cu]Cu-SarAr-h-R3. The imaging data were reconstructed and analyzed using Interview Fusion Software to generate three-dimensional (3D) projections and volumes of interest (VOI). The total radioactivity uptake was calculated for different regions of interest, including the whole body, chest, cardiac region and abdomen. Statistical methods, such as calculating means, standard deviations, and performing two-tailed student's t-tests, were employed to evaluate the data and assess significance between groups. Elevated levels of radioactivity in the abdomen, intestines, liver/spleen, or bone were deemed unfavorable. In contrast to Intravenous (IV) administration, intraperitoneal (IP) injection of [89Zr]Zr-DFO-h-R3 resulted in high levels of radioactivity in the spleen and femoral bone. Intravenous administration of [64Cu]Cu-DOTA-h-R3 exhibited larger amounts of radioactivity in the intestines, liver/spleen compared to IV injected [64Cu]Cu-SarAr-h-R3. [64Cu]Cu-SarAr-h-R3 and [89Zr]Zr-DFO-h-R3 may be considered for future exploration in EGFR-overexpressing cancers and/or correlation analysis with tissue analyses for h-R3 expression in situ.