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J Nucl Med. 2008; 49 (Supplement 1):52P
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Oncology-Basic Science: Basic Science

Imaging - Antibodies and Constructs

Pretargeted immunoPET imaging of CEA-expressing tumors using a Ga-68 labeled peptide

Otto Boerman1, Robert Sharkey2, Gerben Franssen1, Chien-Hsing Chang3, Edmund Rossi3, William McBride3, Rafke Schoffelen1, Winette van der Graaf1, Wim Oyen1 and David Goldenberg2

1 Nuclear Medicine, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands; 2 Garden State Cancer Center, Belleville, New Jersey; 3 Immunomedics, Morris Plains, New Jersey

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Objectives: We have developed a flexible pretargeting system using trivalent anti-CEA x anti-HSG (histamine-succinyl-glycine) bispecific antibodies (bsAb) produced using the dock-and-lock technology. Tumors that are pretargeted with this bsAb can be targeted with HSG-conjugated peptides. We have used Ga-68-labeled peptide DOTA-YK(HSG)EK(HSG)-NH2 for PET imaging of CEA-expressing tumors.

Methods: Athymic mice with s.c. LS174T tumors were pretargeted with (0.1-10 nmol) bsAb and 16 h later In-111/Ga-68 labeled peptide (10 – 100 pmol) was injected. Four bsAb:peptides ratios were studied: 10:1, 25:1, 50:1 and 100:1. The tumor accumulation of the radiolabeled peptide was studied in biodistribution studies and by dynamic microPET/CT imaging at/during 2 h postinjection.

Results: At bsAb doses up to 2.5 nmol high specific uptake of the bsAb in the tumor was obtained (3.5%ID/g, 16 h p.i.). At a molar bsAb:peptide ratio of 25:1 maximal accumulation of the In-111-labeled peptide in the tumor was observed in this model: 26.2 ± 3.8 %ID/g at 2 h p.i. At optimal conditions very high tumor-to-blood and tumor-to-kidney ratios were obtained: 590 and 6, respectively. The DOTA-conjugated peptide was labeled with Ga-68 at a specific activity of 1500 Ci/mmol. PET/CT imaging of mice pretargeted with 2.5 nmol bsAb that received 10 MBq Ga-68-labeled peptide revealed excellent high contrast images.

Conclusions: Pretargeted immunoPET imaging of CEA-expressing tumors using anti-CEA x anti-HSG bsAb in combination with Ga-68-labeled peptide reveals excellent PET images of s.c. LS174T tumors within 1 h after injection.





This Article
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Right arrow Articles by Boerman, O.
Right arrow Articles by Goldenberg, D.
PubMed
Right arrow Articles by Boerman, O.
Right arrow Articles by Goldenberg, D.