PT  - JOURNAL ARTICLE
AU  - William J. McBride
AU  - Pat Zanzonico
AU  - Robert M. Sharkey
AU  - Carl Norén
AU  - Habibe Karacay
AU  - Edmund A. Rossi
AU  - Michele J. Losman
AU  - Pierre-Yves Brard
AU  - Chien-Hsing Chang
AU  - Steven M. Larson
AU  - David M. Goldenberg
TI  - Bispecific Antibody Pretargeting PET (ImmunoPET) with an <sup>124</sup>I-Labeled Hapten-Peptide
DP  - 2006 Oct 01
TA  - Journal of Nuclear Medicine
PG  - 1678--1688
VI  - 47
IP  - 10
4099  - http://jnm.snmjournals.org/content/47/10/1678.short
4100  - http://jnm.snmjournals.org/content/47/10/1678.full
SO  - J Nucl Med2006 Oct 01; 47
AB  - We previously described a highly flexible bispecific antibody (bs-mAb) pretargeting procedure using a multivalent, recombinant anti-CEA (carcinoembryonic antigen) × 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 × 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 1–2 h. Tumor uptake measured 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 radioiodinated 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.