دورية أكاديمية
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.
| العنوان: | 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. |
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| المؤلفون: | Rogers BE; Department of Radiation Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, 35294, USA., Curiel DT, Mayo MS, Laffoon KK, Bright SJ, Buchsbaum DJ |
| المصدر: | Cancer [Cancer] 1997 Dec 15; Vol. 80 (12 Suppl), pp. 2419-24. |
| نوع المنشور: | Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley Country of Publication: United States NLM ID: 0374236 Publication Model: Print Cited Medium: Print ISSN: 0008-543X (Print) Linking ISSN: 0008543X NLM ISO Abbreviation: Cancer Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2005- >: Hoboken, NJ : Wiley Original Publication: New York [etc.] Published for the American Cancer Society by J. Wiley [etc.] |
| مواضيع طبية MeSH: | Adenoviridae/*genetics , Bombesin/*pharmacokinetics , Iodine Radioisotopes/*therapeutic use , Ovarian Neoplasms/*radiotherapy , Receptors, Bombesin/*biosynthesis, Animals ; Female ; Genetic Vectors ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Receptors, Bombesin/genetics ; Tissue Distribution ; Tumor Cells, Cultured |
| مستخلص: | Background: The adenoviral vector, AdCMVGRPr, has been used to induce the expression of the murine gastrin-releasing peptide receptor (GRPr) both in vitro and in vivo. A bombesin analogue ([125I]-mIP-bombesin) has been shown to bind with high affinity to GRPr and to localize to intraperitoneal (i.p.) ovarian tumors 2 days after induction of GRPr in an athymic nude mouse model. The present study was conducted to determine the level of localization of [(125/131)I]-mIP-bombesin in the tumors at 2, 4, and 7 days after AdCMVGRPr administration and to determine the feasibility of giving multiple doses of [131I]-mIP-bombesin for therapy. 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 infection by using a radiolabeled bombesin-binding assay. Biodistribution studies utilized athymic nude mice inoculated i.p. with SKOV3.ip1 cells. The tumors were induced to express GRPr with an i.p. injection of AdCMVGRPr followed by administration of [125I]-mIP-bombesin 2 days later (AdCMVLacZ or saline was used for negative controls). In addition, the tumor localization of [125I]-mIP-bombesin was determined 4 and 7 days after AdCMVGRPr administration. The tumor localization of [131I]-mIP-bombesin was compared with [125I]-mIP-bombesin in this in vivo model. Results: SKOV3.ip1 cells infected with AdCMVGRPr resulted in 80.3 +/- 5.9% binding of [125I]-Tyr4-bombesin at 2 days after infection, which decreased to 46.8 +/- 0.4% at 4 days and to 17.7 +/- 0.1% at 7 days. The biodistribution study showed that the tumor localization (14.9 +/- 8.2% injected dose/gram; ID/g) of [125I]-mIP-bombesin 2 days after administration of AdCMVGRPr was significantly greater than its localization in other organs (P < 0.003) and was significantly greater than in AcCMVLacZ- and saline-treated mice (P < 0.003). Injections of [125I]-mIP-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 localization at longer times after AdCMVGRPr infection correlated with in vitro results. The tumor uptake of [125I]-mIP-bombesin was comparable to the uptake of [131I]-mIP-bombesin (21.2 +/- 8.3% ID/g versus 15.4 +/- 5.6% ID/g, respectively), as was the normal tissue biodistribution. Conclusions: The expression of GRPr in human ovarian cancer cells can be accomplished both in vitro and in vivo by using AdCMVGRPr, with the in vivo tumor localization of [125I]-mIP-bombesin being significantly greater than in control animals. The tumor localization of [125I]-mIP-bombesin and [131I]-mIP-bombesin at 2 days after AdCMVGRPr was comparable in a mouse model of human ovarian carcinoma. Injections of [125I]-mIP-bombesin at Days 4 and 7 after AdCMVGRPr infection resulted in tumor localization of [125I]-mIP-bombesin but at a level lower than 2 days. Thus, the total amount of radioactivity delivered to the tumor should be increased by multiple injections of [131I]-mIP-bombesin, which would be required for a therapeutic effect. |
| المشرفين على المادة: | 0 (Iodine Radioisotopes) 0 (Receptors, Bombesin) PX9AZU7QPK (Bombesin) |
| تواريخ الأحداث: | Date Created: 19971224 Date Completed: 19980102 Latest Revision: 20190620 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1002/(sici)1097-0142(19971215)80:12+<2419::aid-cncr13>3.3.co;2-5 |
| PMID: | 9406692 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 0008-543X |
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| DOI: | 10.1002/(sici)1097-0142(19971215)80:12+<2419::aid-cncr13>3.3.co;2-5 |