In vivo imaging and specific targeting of P-glycoprotein expression in multidrug resistant nude mice xenografts with [(125)I]MRK-16 monoclonal antibody Journal Article
| Authors: | Scott, A. M.; Rosa, E.; Mehta, B. M.; Divgi, C. R.; Finn, R. D.; Biedler, J. L.; Tsuruo, T.; Kalaigian, H.; Larson, S. M. |
| Article Title: | In vivo imaging and specific targeting of P-glycoprotein expression in multidrug resistant nude mice xenografts with [(125)I]MRK-16 monoclonal antibody |
| Abstract: | Multidrug resistance (MDR) in tumors is associated with P-glycoprotein (Pgp) expression. In vivo quantitation of Pgp may allow MDR to be evaluated noninvasively prior to treatment planning. The purpose of this study was to radiolabel MRK-16, a monoclonal antibody that targets an external epitope of P-glycoprotein, and perform in vivo quantitation of P-glycoprotein in a MDR xenograft nude mouse model. MRK-16 was labeled with 125I by the iodogen method, with subsequent purification by size exclusion chromatography. Groups of 10 Balb/c mice were each xenografted with colchicine-resistant or -sensitive neuroblastoma cell lines, respectively. Whole body clearance and tumor uptake over time was quantitated by gamma camera imaging, and biodistribution studies were performed with [125I]MRK-16 and an isotype matched control antibody, A33. Quantitative autoradiography and immunohistochemistry analysis of tumors was also evaluated to confirm specific targetting of [125I]MRK-16. Peak tumor uptake was at 2-3 days post-injection, and was significantly greater in resistance compared to sensitive tumors (mean % injected dose/g ± SD) (18.76 ± 2.94 vs 10.93 ± 0.96; p < 0.05). Quantitative autoradiography verified these findings (19.13 ± 0.622 vs 12.08 ± 0.38, p < 0.05). Specific binding of [125I]MRK-16 was confirmed by comparison to [131I]A33 in biodistribution studies, and localized to cellular components of tissue stroma by comparison of histologic and autoradiographic sections of sensitive and resistant tumors. Immunoblot analysis demonstrated a 4.5-fold difference in P-glycoprotein expression between sensitive and resistant cell lines without colchicine selective pressure. We conclude that in vivo quantitation of P-glycoprotein in MDR tumors can be performed with [125I]MRK-16. These findings suggest a potential clinical application for radiolabeled MRK-16 in the in vivo evaluation of multidrug resistance in tumors. © 1995. |
| Keywords: | immunohistochemistry; controlled study; unclassified drug; human cell; doxorubicin; mouse; animal; mice; gene expression; animal experiment; vincristine; tumor xenograft; mice, inbred balb c; monoclonal antibody; antibodies, monoclonal; iodine 125; nude mouse; tissue distribution; iodine radioisotopes; mice, nude; neuroblastoma; transplantation, heterologous; dactinomycin; autoradiography; multidrug resistance; p-glycoprotein; colchicine; drug resistance, multiple; glycoprotein p; human; female; article; support, u.s. gov't, non-p.h.s.; monoclonal antibody mrk 16 |
| Journal Title: | Nuclear Medicine and Biology |
| Volume: | 22 |
| Issue: | 4 |
| ISSN: | 0969-8051 |
| Publisher: | Elsevier Science Inc. |
| Date Published: | 1995-05-01 |
| Start Page: | 497 |
| End Page: | 504 |
| Language: | English |
| DOI: | 10.1016/0969-8051(94)00127-6 |
| PUBMED: | 7550027 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
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