Bispecific antibody pretargeting PET (ImmunoPET) with an (124)I-labeled hapten-peptide Journal Article
| Authors: | McBride, W. J.; Zanzonico, P.; Sharkey, R. M.; Norén, C.; Karacay, H.; Rossi, E. A.; Losman, M. J.; Brard, P. Y.; Chang, C. H.; Larson, S. M.; Goldenberg, D. M. |
| Article Title: | Bispecific antibody pretargeting PET (ImmunoPET) with an (124)I-labeled hapten-peptide |
| Abstract: | We previously described a highly flexible bispecific antibody (bs-mAb) pretargeting procedure using a multivalent, recombinant anti-CEA (carcinoembryonic antigen) x anti-HSG (histamine-succinyl-glycine) fusion protein with peptides radiolabeled with 111In, 90Y, 177Lu, and 99mTc. The objective of this study was to develop a radioiodination procedure primarily to assess PET imaging with 124I. Methods: A new peptide, DOTA-D-Tyr-D-Lys(HSG)-D-Glu-D-Lys(HSG)- NH2 (DOTA is 1,4,7, 10-tetraazacyclododecane-N,N′,N″, N‴-tetraacetic acid), was synthesized and conditions were established for radioiodination with yields of ∼70% for 131I and 60% for 124I. Pretargeting with the 131I- and 124I- labeled peptide was tested in nude mice bearing LS174T human colonic tumors that were first given the anti-CEA x anti-HSG bs-mAb. Imaging (including small-animal PET) and necropsy data were collected at several intervals over 24 h. Comparisons were made between animals given 124I-anti-CEA Fab′, 18F-FDG, the same peptide radiolabeled with 111In and pretargeted with the bs-mAb, and the radioiodinated peptide alone. Results: The radioiodinated peptide alone cleared quickly from the blood with no evidence of tumor targeting, but when pretargeted with the bs-mAb, tumor uptake increased 70-fold, with efficient and rapid clearance from normal tissues, allowing clear visualization of tumor within 122 h. Tumor uptakemeasured at necropsy was 3- to 15-fold higher and tumor-to-blood ratios were 10- to 20-fold higher than those for 124I-Fab′ at 1 and 24 h, respectively. Thyroid and stomach uptake was observed with the radio-iodinated peptide several hours after injection (animals were not premedicated to reduce uptake in these tissues), but gastric uptake was much more pronounced with 124I-Fab′. Tumor visualization with 18F-FDG at ∼1.5 h was also good but showed substantially more uptake in several normal tissues, making image interpretation in the pretargeted animals less ambiguous than with 18F-FDG. Conclusion: Bispecific antibody pretargeting has a significant advantage for tumor imaging over directly radiolabeled antibodies and could provide additional enhancements for oncologic imaging, particularly for improving targeting specificity as compared with 18F-FDG. Copyright © 2006 by the Society of Nuclear Medicine, Inc. |
| Keywords: | controlled study; unclassified drug; nonhuman; comparative study; positron emission tomography; mouse; animal; metabolism; animals; mice; animal tissue; carcinoembryonic antigen; analytic method; animal experiment; colonic neoplasms; cell line, tumor; monoclonal antibody; chemistry; iodine 131; diagnostic agent; radioactive iodine; isotope labeling; xenograft; nude mouse; tissue distribution; iodine radioisotopes; mice, nude; whole body imaging; colon cancer; colon tumor; tumor cell line; fluorodeoxyglucose f 18; positron-emission tomography; peptides; radiopharmaceutical agent; scintiscanning; transplantation, heterologous; imaging; iodine 124; neoplasm transplantation; pet; oligopeptides; cancer transplantation; immunoglobulin f(ab) fragment; oligopeptide; single heterocyclic rings; radioimmunoassay; heterocyclic compounds, 1-ring; radioimmunodetection; radioiodination; antibodies, bispecific; bispecific antibody; pretargeting; 1,4,7,10 tetraazacyclododecane 1,4,7,10 tetraacetic acid dextro tyrosyl dextro lysyl (histamine succinyl glycine)dextro glutamyl dextro lysin (histamine succinyl glycine)amide i 131; 1,4,7,10 tetraazacyclododecane 1,4,7,10 tetraacetic acid dextro tyrosyl dextro lysyl (histamine succinyl glycine)dextro glutamyl dextro lysin (histamine succinyl glycine)amide in 111; 1,4,7,10 tetraazacyclododecane 1,4,7,10 tetraacetic acid dextro tyrosyl dextro lysyl dextro glutamyl dextro lysin (histamine succinyl glycine)amide i 124; 1,4,7,10 tetraazacyclododecane 1,4,7,10 tetraacetic acid dextro tyrosyl dextro lysyl dextro glutamyl dextro lysin (histamine succinyl glycine)amide in 111; hbs 14 i 125; histamine succinyl glycine monoclonal antibody; indium chloride in 111; dota tyrosyl lysyl(histaminyl succinyl glycyl) glutamyl lysyl(histaminyl succinyl glycyl)amide; dota-tyrosyl-lysyl(histaminyl-succinyl-glycyl)-glutamyl-lysyl(histaminyl-succinyl-glycyl)amide; hapten; haptens |
| Journal Title: | Journal of Nuclear Medicine |
| Volume: | 47 |
| Issue: | 10 |
| ISSN: | 0161-5505 |
| Publisher: | Society of Nuclear Medicine |
| Date Published: | 2006-10-01 |
| Start Page: | 1678 |
| End Page: | 1688 |
| Language: | English |
| PUBMED: | 17015905 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 44" - "Export Date: 4 June 2012" - "CODEN: JNMEA" - "Source: Scopus" |
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