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

IntroductionThe 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 64Cu 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).MethodsSmall animal PET scans were performed on five different human cancer xenograft mice models 1 h and 22 h post injection (p.i.) of 64CuCl2. 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 22 h scan.ResultsA relatively high tumor uptake of 64Cu was seen in four out of five tumor types and an increase in 64Cu accumulation was seen in three out of five tumor types between 1 h and 22 h p.i. No relationship was found between tumor uptake of 64Cu and gene expression of CTR1.ConclusionsThe relatively high, time- and tumor type dependent 64Cu 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.