Evaluation of a fluorinated 2-nitroimidazole binding to hypoxic cells in tumor-bearing rats by 19F magnetic resonance spectroscopy and immunohistochemistry.
We have examined a hexafluorinated 2-nitroimidazole, CCI-103F, as a probe for hypoxic tumor cells by in vivo 19F magnetic resonance spectroscopy (MRS). Following initial intraperitoneal injections of the drug in tumor-bearing (Dunning R3327-AT1-Matlylu) rats, 19F spectra were obtained on an Otsuka 2.0T Vivospec spectrometer using a 1.5-cm surface coil. Signal at 1- and 2-h time points indicated initial biodistribution of drug in the tumor. At 4 and 8 h, a progressive increase in signal intensity was observed, indicating retention of drug within the tumor. Tumor signal remained detectable in 4 of 10 rats at 24 h, indicating possible nitroreductive bioactivation by hypoxic cells. Immunohistochemistry of these tumors revealed a staining pattern consistent with labeling of hypoxic cells. No detectable 19F signal was found at 24 h for the other rats, indicating complete washout of unbound drug. Immunohistochemical assessment of these tumors revealed some staining for bound drug at the periphery of necrotic zones. 31P-MRS of the tumors showed good correlation with the presence or absence of hypoxia as evaluated by 19F-MRS, T1- and T2-weighted images, and immunohistochemistry. These results provide the groundwork for further studies using this misonidazole analog for noninvasive identification of hypoxic tumor cells in vivo by MRS.
Kwock
L
L
Department of Radiology, University of North Carolina, Chapel Hill 27599.
Gill
M
M
McMurry
H L
HL
Beckman
W
W
Raleigh
J A
JA
Joseph
A P
AP
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D015687:Cell Hypoxia; D005069:Evaluation Studies as Topic; D007150:Immunohistochemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009593:Nitroimidazoles; D011471:Prostatic Neoplasms / Q000473:pathology*; D051381:Rats; D005466:Fluorocarbons
D009593:Nitroimidazoles; C049948:CCI 103F; D005466:Fluorocarbons