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Gamma Camera Dual Imaging with a Somatostatin Receptor and Thymidine Kinase after Gene Transfer with a Bicistronic Adenovirus in Mice¹

¹ From the Departments of Radiology (K.R.Z., T.R.C.), Radiation Oncology (D.J.B., B.E.R.), Pathology (W.E.G.), Division of Human Gene Therapy, Departments of Medicine, Surgery, and Pathology (V.N.K., D.T.C.), and Gene Therapy Center (K.R.Z., V.N.K., D.J.B., N.B., D.T.C., B.E.R.), University of Alabama at Birmingham, Boshell Bldg, BDB 11, 1530 3rd Ave S, Birmingham, AL 35294-0012. Received February 21, 2001; revision requested March 29; revision received August 2; accepted September 17. Supported by the National Cancer Institute grants CA80104 and CO97110. Address correspondence to K.R.Z. (e-mail: kurtzinn@uab.edu).

PURPOSE: To compare two systems for assessing gene transfer to cancer cells and xenograft tumors with noninvasive gamma camera imaging.

MATERIALS AND METHODS: A replication-incompetent adenovirus encoding the human type 2 somatostatin receptor (hSSTr2) and the herpes simplex virus thymidine kinase (TK) enzyme (Ad-hSSTr2-TK) was constructed. A-427 human lung cancer cells were infected in vitro and mixed with uninfected cells at different ratios. A-427 tumors in nude mice (n = 23) were injected with 1 x 10⁶ to 5 x 10⁸ plaque-forming units (pfu) of Ad-hSSTr2-TK. The expressed hSSTr2 and TK proteins were imaged owing to internally bound, or trapped, technetium 99m (^99mTc)-labeled hSSTr2-binding peptide (P2045) and radioiodinated 2'-deoxy-2'-fluoro-ß-D-arabinofuranosyl-5-iodouracil (FIAU), respectively. Iodine 125 (¹²⁵I)-labeled FIAU was used in vitro and iodine 131 (¹³¹I)-labeled FIAU, in vivo. The ^99mTc-labeled P2045 and ¹²⁵I- or ¹³¹I-labeled FIAU were imaged simultaneously with different window settings with an Anger gamma camera. Treatment effects were tested with analysis of variance.

RESULTS: Infected cells in culture trapped ¹²⁵I-labeled FIAU and ^99mTc-labeled P2045; uptake correlated with the percentage of Ad-hSSTr2-TK-positive cells. For 100% of infected cells, 24% ± 0.4 (mean ± SD) of the added ^99mTc-labeled P2045 was trapped, which is significantly lower (P < .05) than the 40% ± 2 of ¹²⁵I-labeled FIAU that was trapped. For the highest Ad-hSSTr2-TK tumor dose (5 x 10⁸ pfu), the uptake of ^99mTc-labeled P2045 was 11.1% ± 2.9 of injected dose per gram of tumor (thereafter, dose per gram), significantly higher (P < .05) than the uptake of ¹³¹I-labeled FIAU at 1.6% ± 0.4 dose per gram. ^99mTc-labeled P2045 imaging consistently depicted hSSTr2 gene transfer in tumors at all adenovirus doses. Tumor uptake of ^99mTc-labeled P2045 positively correlated with Ad-hSSTr2-TK dose; ¹³¹I-labeled FIAU tumor uptake did not correlate with vector dose.

CONCLUSION: The hSSTr2 and TK proteins were simultaneously imaged following dual gene transfer with an adenovirus vector.

© RSNA, 2002

Index terms: Animals • Experimental studies • Genes and genetics • Molecular analysis • Radionuclide imaging

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