Abstract | UNLABELLED: METHODS: [125I]-mIP- bombesin was synthesized and compared with [125I]-Tyr4- bombesin in internalization assays using BNR-11 cells (mouse fibroblast cells stably transfected with GRPr) over a 24-hr period. In vitro binding assays used BNR-11, and A427, HeLa and SKOV3.ip1 human cancer cells, which were either uninfected or infected with AdCMVGRPr. Biodistribution studies were performed in normal BALB/c mice and in athymic nude mice bearing orthotopic SKOV3.ip1 ovarian cancer tumors. The SKOV3.ip1 tumors were induced to express GRPr with the AdCMVGRPr adenoviral vector. RESULTS: Internalization assays showed that [125I]-Tyr4- bombesin was rapidly internalized and catabolized at 37 degrees C with approximately 10% of the radioactivity remaining intracellularly at 4 hr, compared with approximately 30% with [125I]-mIP- bombesin. HeLa, A427 and SKOV3.ip1 cells were all induced to express levels of GRPr that were higher than those seen with the positive control BNR-11 cells. Normal mice showed a lower level of radioactivity in both the blood and thyroid for [125I]-mIP- bombesin [0.26% +/- 0.10% injected dose per gram (ID/g) and 0.24% +/- 0.05% ID] than for [125I]-Tyr4- bombesin (3.5% +/- 1.6% ID/g and 5.2% +/- 4.4% ID) at 4 hr postinjection. Mice bearing intraperitoneal (i.p.) SKOV3.ip1 tumors and given AdCMVGRPr i.p. 5 days after tumor cell inoculation followed by [125I]-mIP- bombesin i.p. at day 7 showed 16.5% +/- 4.8% ID/g in tumor compared with 5.9% +/- 3.0% ID/g with [125I]-Tyr4- bombesin at 4 hr postinjection. Tumor bearing mice given saline or a control adenovirus expressing the beta-galactosidase (LacZ) gene showed significantly lower tumor uptake values of both bombesin peptides. CONCLUSION: Internalization assays showed that [125I]-mIP- bombesin has favorable characteristics compared with [125I]-Tyr4- bombesin with regards to cellular internalization and retention. The results demonstrate successful in vitro and in vivo transduction of human tumor cells with a recombinant adenoviral vector-expressing GRPr. Additionally, tumors transduced in vivo to express GRPr demonstrated significantly greater localization of [125I]-mIP- bombesin when compared with [125I]-Tyr4- bombesin.
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Authors | B E Rogers, M E Rosenfeld, M B Khazaeli, G Mikheeva, M A Stackhouse, T Liu, D T Curiel, D J Buchsbaum |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 38
Issue 8
Pg. 1221-9
(Aug 1997)
ISSN: 0161-5505 [Print] United States |
PMID | 9255155
(Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Iodine Radioisotopes
- Peptide Fragments
- Receptors, Bombesin
- bombesin(8-13)-NH2, N-(3-iodobenzoyl)glutamyl-des-Met(14)-
- bombesin, Tyr(4)-
- Bombesin
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Topics |
- Adenoviridae
- Animals
- Bombesin
(analogs & derivatives, pharmacokinetics)
- Female
- Gene Transfer Techniques
- Genetic Vectors
- Humans
- Iodine Radioisotopes
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Ovarian Neoplasms
(diagnostic imaging, metabolism)
- Peptide Fragments
(pharmacokinetics)
- Radionuclide Imaging
- Receptors, Bombesin
(biosynthesis)
- Tissue Distribution
- Tumor Cells, Cultured
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