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Tumor localization of a radiolabeled bombesin analogue in mice bearing human ovarian tumors induced to express the gastrin-releasing peptide receptor by an adenoviral vector

✍ Scribed by Buck E. Rogers; David T. Curiel; Matthew S. Mayo; Kim K. Laffoon; Sheila J. Bright; Donald J. Buchsbaum


Publisher
John Wiley and Sons
Year
1997
Tongue
English
Weight
136 KB
Volume
80
Category
Article
ISSN
0008-543X

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✦ Synopsis


METHODS. Human ovarian cancer cells (SKOV3.ip1) were infected in vitro with

AdCMVGRPr and were assayed for receptor expression at 2, 4, and 7 days after 2 Department of Medicine, Comprehensive Caninfection by using a radiolabeled bombesin-binding assay. Biodistribution studies cer Center, University of Alabama at Birutilized athymic nude mice inoculated i.p. with SKOV3.ip1 cells. The tumors were mingham, Birmingham, Alabama.

induced to express GRPr with an i.p. injection of AdCMVGRPr followed by adminis-3 Gene Therapy Program, Comprehensive Cantration of [ 125 I]-mIP-bombesin 2 days later (AdCMVLacZ or saline was used for cer Center, University of Alabama at Birnegative controls). In addition, the tumor localization of [ 125 I]-mIP-bombesin was mingham, Birmingham, Alabama. determined 4 and 7 days after AdCMVGRPr administration. The tumor localization of [ 131 I]-mIP-bombesin was compared with [ 125 I]-mIP-bombesin in this in vivo model. RESULTS. SKOV3.ip1 cells infected with AdCMVGRPr resulted in 80.3 { 5.9% bind-Presented at the Sixth Conference on Radioiming of [ 125 I]-Tyr 4 -bombesin at 2 days after infection, which decreased to 46.8 { munodetection and Radioimmunotherapy of 0.4% at 4 days and to 17.7 { 0.1% at 7 days. The biodistribution study showed Cancer, Princeton, New Jersey, October 10-12, that the tumor localization (14.9 { 8.2% injected dose/gram; ID/g) of [ 125 I]-mIP-1996.

bombesin 2 days after administration of AdCMVGRPr was significantly greater than its localization in other organs (P õ 0.003) and was significantly greater than in Supported by Grants DE-FG05-93ER61654 and AcCMVLacZ-and saline-treated mice (P õ 0.003). Injections of [ 125 I]-mIP-DE-FG02-96ER62181 from the U.S. Department of Energy.

bombesin at 4 and 7 days after a single AdCMVGRPr administration showed tumor localization of 4.5 { 3.0% ID/g at Day 4 and 3.9 { 3.5% ID/g at Day 7. The decreased The authors thank Sally Lagan for help in the localization at longer times after AdCMVGRPr infection correlated with in vitro preparation of this paper and Christine Olsen results. The tumor uptake of [ 125 I]-mIP-bombesin was comparable to the uptake for technical assistance.

of [ 131 I]-mIP-bombesin (21.2 { 8.3% ID/g versus 15.4 { 5.6% ID/g, respectively), as was the normal tissue biodistribution.