Investigation of copper-PTSM as a PET tracer for tumor blood flow |
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| Affiliation: | 1. The Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Mo., U.S.A.;2. Department of Surgery, Washington University School of Medicine, St Louis, Mo., U.S.A.;3. Purdue University, School of Pharmacy, West Lafayette, In., U.S.A.;1. Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany;2. Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany;3. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada;1. Collaboration for Cancer Outcomes Research and Evaluation (CCORE), Ingham Institute for Applied Medical Research, Liverpool Hospital, UNSW, Sydney, Australia;2. Department of Radiation Oncology, Prince of Wales Hospital, Sydney, Australia;3. University of New South Wales, Sydney, Australia;4. University of Western Sydney, Australia;5. Division of Cancer Care and Epidemiology, Queen’s University Cancer Research Institute, Kingston, Canada;1. Institute of Applied Physics and Computational Mathematics, Beijing 100094, China;2. Key Laboratory of Nuclear Data, China Institute of Atomic Energy, P.O. Box 275(41), Beijing 102413, China;3. Department of Physics, Nankai University, Tianjin 300071, China |
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| Abstract: | Copper-PTSM has been shown in previous studies to act as a fluid microsphere and to be useful in quantitating blood flow in brain, myocardium, and kidneys. In this study we have evaluated this agent as a PET tumor blood flow agent. 64Cu- or 67Cu-labeled Cu-PTSM was administered (i.v.) to Golden Syrian hamsters with colorectal carcinoma cell implants (GW39). One minute prior to sacrifice (10–60 min after Cu-PTSM was administered) 125I-iodoantipyrine (125I-IAP), an agent known to measure tumor blood flow, was administered intravenously by a 3-stage, 1 min ramp infusion. Following sacrifice, samples of tumor and brain were removed (within 40 s) and the tumor and brain levels of Cu-PTSM and iodoantipyrine determined. Since the brain uptake of both Cu-PTSM and IAP is perfusion rate limited, the brain was used as a reference organ to normalize tumor levels of the two tracers. The plot of Cu-PTSM versus 125I-IAP tumor/brain ratios showed a good linear correlation (r value of 0.97), suggesting that Cu-PTSM could be used to quantify tumor blood flow. Since the mechanism of Cu-PTSM trapping is likely to be due to glutathione levels in the tissue, and because tumor tissue glutathione levels might vary, the temporal uptake of Cu-PTSM was investigated by PET imaging both the tumor-bearing hamsters and ~300 g Copenhagen rats bearing R3227 prostate tumors. The tumors were clearly visualized and the retained copper radioactivity in the tumor was constant over the 30 min imaging period. |
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