Investigation of copper-PTSM as a PET tracer for tumor blood flow.
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 40s) 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 approximately 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.
Mathias
C J
CJ
Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110.
Welch
M J
MJ
Perry
D J
DJ
McGuire
A H
AH
Zhu
X
X
Connett
J M
JM
Green
M A
MA
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives; D001921:Brain / Q000098:blood supply; D003110:Colonic Neoplasms / Q000473:pathology; D003300:Copper; D003331:Coronary Vessels / Q000502:physiology; D006224:Cricetinae; D006801:Humans; D007668:Kidney / Q000098:blood supply; D008297:Male; D008647:Mesocricetus; D008863:Microspheres; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply*; D009942:Organometallic Compounds; D011471:Prostatic Neoplasms / Q000473:pathology; D013882:Thiosemicarbazones; D014055:Tomography, Emission-Computed
D009942:Organometallic Compounds; D013882:Thiosemicarbazones; C052629:copper pyruvaldehyde bis(N(4)-methylthiosemicarbazone) complex; D003300:Copper; D000983:Antipyrine; C008135:iodoantipyrine