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Measurement of PDT-Induced Hypoxia in Dunning Prostate Tumors by Iodine-123-Iodoazomycin Arabinoside

Departments of Radiation Oncology, Nuclear Medicine and Surgery, Cross Cancer Institute, Edmonton, Alberta, Canada
Departments of Radiology and Diagnostic Imaging and Surgery and Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada

Correspondence: For correspondence or reprints contact: J. Donald Chapman, Tumor Biology and Biophysics, Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111.

ABSTRACT

Photodynamic therapy (PDT) is known to produce vascular damage in solid tumors resulting in secondary ischemia and tumor cell death from hypoxia. The oxygenation status of both non-treated and PDT-treated Dunning R3327-AT prostate tumors growing in Fischer X Copenhagen rats was investigated with the novel hypoxic marker, ¹²³I-iodoazomycin arabinoside (IAZA). Both qualitative and quantitative data from planar scintigraphy of anesthetized tumor-bearing rats showed increased retention of ^123>I-IAZA in tumors treated with PDT. Tumor perfusion in the same tumors was measured with ^99mTc-hexamethylpropyleneamineoxime (HMPAO). Region of interest analyses revealed an inverse correlation between tumor hypoxia measured by ¹²³I-IAZA and tumor perfusion as measured by ^99mTc-HMPAO (coefficient of correlation, r = –0.72). Planar images of 2-mm frozen sections from a large tumor showed ¹²³I-IAZA selectively retained in the region that had been treated with PDT. This and other iodinated azomycin nucleosides, labeled with ¹²³I, show promise for monitoring tumor oxygenation status noninvasively and, in particular, for monitoring the effectiveness of interstitial PDT treatments where perfusion shutdown is a major mechanism of tumor response.

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