Preclinical radioimmunotargeting of folate receptor alpha using the monoclonal antibody conjugate DOTA-MORAb-003 Journal Article
| Authors: | Smith-Jones, P. M.; Pandit-Taskar, N.; Cao, W.; O'Donoghue, J.; Philips, M. D.; Carrasquillo, J.; Konner, J. A.; Old, L. J.; Larson, S. M. |
| Article Title: | Preclinical radioimmunotargeting of folate receptor alpha using the monoclonal antibody conjugate DOTA-MORAb-003 |
| Abstract: | Introduction: The in vitro and in vivo behavior of the radiolabeled monoclonal antibody MORAb-003 was investigated as a prelude to a clinical trial. Methods: The cellular retention of 111In- and 131I-labeled MORAb-003 was investigated using IGROV1 and SW620 cells. Biodistribution studies in tumor-bearing mice were performed with the more favorable agent. Results: Five 1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″-tetraacetic acid (DOTA) molecules were conjugated to MORAb-003 with no apparent loss of immunoreactivity. Radiolabeled MORAb-003 had a high affinity for the folate receptor alpha (FRA) expressed by both IGROV1 and SW620 cells and was found to bind to around 8×105 and 7×105 sites/cell, respectively. Both cancer cell lines were found to internalize both 131I- and 111In-labeled MORAb-003, but 111In was retained and 131I was released as iodide. In athymic mice, 111In-DOTA-MORAb-003 was cleared from the blood with a single exponential biological clearance rate of 110 h. The uptake in SW620 tumors was 32±5%ID/g after 4 days. The clearance rate of activity from normal organs such as liver, kidney and spleen was similar to the blood clearance and was 5.36%ID/g, 4.03%ID/g and 4.36%ID/g at 1 day postinjection and 2.14%ID/g, 1.65%ID/g and 3.74%ID/g after 8 days, respectively. In a pilot clinical study, the biodistribution and tumor targeting of 111In-MORAb-003 was assessed in three patients undergoing treatment with cold MORAb-003. Conclusion: MORAb-003 is an attractive antibody for radioimmunoscintigraphy and possibly radioimmunotherapy of FRA-expressing cancers in addition to its potential direct therapeutic effects. © 2008 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; human cell; clinical trial; case report; nonhuman; radiopharmaceuticals; ovarian neoplasms; animal cell; mouse; animals; mice; animal tissue; neoplasm recurrence, local; protein targeting; animal experiment; animal model; drug evaluation, preclinical; cell line, tumor; immunoreactivity; monoclonal antibody; drug dose escalation; antibodies, monoclonal; indium radioisotopes; iodine 131; drug distribution; drug uptake; isotope labeling; tissue distribution; iodine radioisotopes; mice, nude; pilot projects; carrier proteins; drug clearance; metabolic clearance rate; phase 1 clinical trial; drug half life; indium 111; drug binding; 1,4,7,10 tetraazacyclododecane 1,4,7,10 tetraacetic acid; drug conjugation; monoclonal antibody morab 003; receptors, cell surface; folate receptor alpha; neoplasms, glandular and epithelial; immunoconjugates; folate receptor; heterocyclic compounds, 1-ring; radioimmunodetection; dota; in-111; in-131; biological transport, active |
| Journal Title: | Nuclear Medicine and Biology |
| Volume: | 35 |
| Issue: | 3 |
| ISSN: | 0969-8051 |
| Publisher: | Elsevier Science Inc. |
| Date Published: | 2008-04-01 |
| Start Page: | 343 |
| End Page: | 351 |
| Language: | English |
| DOI: | 10.1016/j.nucmedbio.2007.12.008 |
| PUBMED: | 18355690 |
| PROVIDER: | scopus |
| PMCID: | PMC2676680 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 18" - "Export Date: 17 November 2011" - "CODEN: NMBIE" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
-
156Konner -
1Cao -
344Pandit-Taskar -
151O'Donoghue -
140Carrasquillo -
67
Smith-Jones -
959Larson -
593Old
Related MSK Work