High tumor uptake of (64)Cu: implications for molecular imaging of tumor characteristics with copper-based PET tracers

Introduction: The use of copper-based positron emission tomography (PET) tracers in cancer studies is increasing. However, as copper has previously been found in high concentrations in human tumor tissue in vivo, instability of PET tracers could result in tumor accumulation of non-tracer-bound radioactive copper that may influence PET measurements. Here we determine the degree of (64)Cu uptake in five commonly used human cancer xenograft models in mice. Additionally, we compare copper accumulation in tumor tissue to gene expression of human copper transporter 1 (CTR1).

Methods: Small animal PET scans were performed on five different human cancer xenograft mice models 1h and 22h post injection (p.i.) of (64)CuCl2. Regions of interest (ROIs) were drawn on tumor tissue and sections of various organs on all images. Quantitative real-time PCR (qPCR) gene expression measurements of CTR1 were performed on tumor samples obtained after the 22h scan.

Results: A relatively high tumor uptake of (64)Cu was seen in four out of five tumor types and an increase in (64)Cu accumulation was seen in three out of five tumor types between 1h and 22h p.i. No relationship was found between tumor uptake of (64)Cu and gene expression of CTR1.

Conclusions: The relatively high, time- and tumor type dependent (64)Cu uptake demonstrated here in five different human cancer xenograft models in mice, emphasizes the importance of validating tracer uptake and indicates that high in vivo stability of copper-based PET tracers is of particular importance because non-tracer-bound copper can accumulate in tumor tissue to a level that could potentially lead to misinterpretation of PET data.