Ultra-low dose 64 Cu-rituximab tracer for a human CD20 mouse model PET imaging

Frezghi Habte ^1* Arutselvan Natarajan ²

• ¹ School of Medicine, Stanford University, Stanford, United States
• ² Department of Radiology, School of Medicine, Stanford University, Stanford, California, United States

and their fragments can be labeled with PET radioisotope (immunoPET) for in vivo diagnostic imaging. Compared to the conventional FDG-PET, immunoPET can be designed to target in vivo cancer-specific antigen expression levels for various tumors and metastasis, which makes immunoPET (iPET) a powerful technique for molecular imaging and therapy monitoring. However, achieving the optimal dose to minimize radioisotope toxicity without compromising the visualization of the smallest tumor is challenging. To find an ultra-minimal tracer dose, we have developed a novel iPET with an intact rituximab Ab labeled with 64 Cu to image human CD20 (hCD20) in a transgenic mouse model for non-Hodgkin's lymphoma (NHL) imaging. Using phantom and in vivo mouse models, we optimized the minimal dose that can be administered in a mouse using a high-specific iPET tracer prepared from 64 Cu-rituximab. A phantom study was used to characterize the scanner capability and limit for imaging using low doses. An ultra-minimal dose administered in a mouse model showed good image quality with high signal-to-noise ratio without compromising quantitative accuracy. The phantom study with below 50 µCi dose level indicated a slight increase in variability due to reduced dose specifically for target regions with lower uptakes (< 3:1 ratio) relative to the background. In vivo study performed with four groups of mice (n=3), each group injected with ~90 µCi, ~50 µCi, ~25 µCi, and ~10 µCi showed a linear increase of tracer uptake measured as percentage injected dose per gram (%ID/g). This tracer has shown high specific uptake in the spleen, where most B-cells are engineered to express hCD20. The study demonstrated that the lowest dose threshold limit for 64 Cu-antibodybased iPET was about 25 µCi while achieving a high-quality image and quantitative accuracy.