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Tumor Uptake of Copper-Diacetyl-Bis(N⁴-Methylthiosemicarbazone): Effect of Changes in Tissue Oxygenation

Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri; and Biomedical Imaging Research Center, Fukui Medical University, Matsuoka, Fukui, Japan

View larger version (11K): [in a new window]   FIGURE 1. Structure of Cu-ATSM.

View larger version (12K): [in a new window]   FIGURE 2. Oxygen probe evaluation of 9L tumors in age-matched rats. (A) Representative oxygenation of tumor in normal untreated animal. (B) Representative oxygenation of tumor in rat that received hydralazine 1 h before pO2 measurements.

View larger version (18K): [in a new window]   FIGURE 3. Correlation of 67Cu-ATSM uptake with oxygen probe measurements in 9L tumors subjected to various degrees of oxygenation (same animals as in Fig. 4). Relative uptake was determined by quantification of 67Cu-ATSM in 1-mm tumor slices using InstantImager (Packard Instrument Co., Meriden, CT). Oxygen measurements were taken 5 min after injection of 67Cu-ATSM; kill was performed 10 min after tracer injection. Hydralazine-treated animals showed significantly higher uptake of 67Cu-ATSM (A, average pO2 = 20.81 ± 7.54 mm Hg, n = 3) than did well-oxygenated animals (C, average pO2 = 45.88 ± 15.99 mm Hg, n = 3). Tumors from control animals showed wide range of 67Cu-ATSM uptake (B, average pO2 = 28.61 ± 8.74 mm Hg, n = 3).

View larger version (31K): [in a new window]   FIGURE 4. Typical autoradiographs of 67Cu-ATSM distribution in 9L tumors with manipulated oxygenation levels. Tumors used were of comparative size, and slices were selected at random from tumors shown in Figures 2 and 3. The hydralazine-treated animals visually show higher uptake of 67Cu-ATSM (A) compared with well-oxygenated animals (C). Control untreated tumors show wide range of 67Cu-ATSM uptake (B). White areas of very low uptake seen within tumors were examined visually and were not necrotic.

View larger version (27K): [in a new window]   FIGURE 5. Typical dual-tracer autoradiograph of two slices of 9L tumor from fasted but otherwise untreated rat, with FDG distribution at 60 min after injection (imaged shortly after kill, left) and 64Cu-ATSM distribution at 10 min after injection (imaged 24 h after kill, right). Difference in regional uptake between tracers is seen clearly.

View larger version (18K): [in a new window]   FIGURE 6. Time-activity curves generated by drawing ROIs over tumors from 61Cu-ATSM PET of rats bearing 9L tumors under varying degrees of oxygenation. Data are normalized to amount of radioactivity injected. , FIO2 10% oxygen:90% nitrogen; , FIO2 100% oxygen; , hydralazine; x, saline.