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Metastatic Human Colonic Carcinoma: Molecular Imaging with Pretargeted SPECT and PET in a Mouse Model¹

¹ From the Center for Molecular Medicine and Immunology, Garden State Cancer Center, 520 Belleville Ave, Belleville, NJ 07109 (R.M.S., H.K., D.M.G.); Citigroup Biomedical Imaging Center and Department of Radiology, Weill Medical College of Cornell University, New York, NY (S.V., S.J.G.); Immunomedics, Morris Plains, NJ (W.J.M., C.H.C.); and IBC Pharmaceuticals, Morris Plains, NJ (E.A.R., C.H.C.). Received February 2, 2007; revision requested April 5; revision received April 20; accepted May 9; final version accepted July 19. Supported in part by grant CDG-06-103 from the New Jersey Department of the Treasury. Address correspondence to R.M.S. (e-mail: rmsharkey{at}gscancer.org).

Purpose: To prospectively determine if a bispecific monoclonal antibody (MoAb) pretargeting method with a radiolabeled hapten peptide can depict small (<0.3 mm in diameter) microdisseminated human colon cancer colonies in the lungs of nude mice.

Materials and Methods: Animal studies were approved in advance by animal care and use committees. Animals injected intravenously with a human colon cancer cell line to establish microdisseminated colonies in the lungs were pretargeted with TF2—a recombinant, humanized, anti–carcinoembryonic antigen (CEA) and anti–histamine-succinyl-glycine (HSG) bispecific MoAb; 21 hours later, a radiolabeled HSG peptide was given. Imaging and necropsy data for tumor-bearing animals given the anti-CEA bispecific MoAb (n = 38, all studies) were compared with those of animals given fluorine 18 (¹⁸F) fluorodeoxyglucose (FDG) (n = 15, all studies), peptide alone (n = 20, all studies), or an irrelevant anti-CD22 bispecific MoAb (n = 12, all studies). Uptake of these agents in the lungs of non–tumor-bearing animals enabled assessment of specificity (n = 15, 4, and 6 for TF2 pretarget, hapten peptide alone, and ¹⁸F-FDG, respectively).

Results: TF2-pretargeting helped localize tumors in the lungs within 1.5 hours of the radiolabeled HSG peptide injection, while the peptide alone, irrelevant bispecific MoAb pretargeted peptide, and ¹⁸F-FDG failed. Necropsy data indicated that the signal in tumor-bearing lungs was five times higher than in blood within 1.5 hours, increasing to 50 times higher by 24 hours. Peptide uptake in tumor-bearing lungs pretargeted with TF2 was nine times higher than in non–tumor-bearing lungs, while it was only 1.5-fold higher with ¹⁸F-FDG or the peptide alone. Micro-positron emission tomographic (PET) images showed discrete uptake in individual metastatic tumor colonies; autoradiographic data demonstrated selective targeting within the lungs, including metastases less than 0.3 mm in diameter.

Conclusion: Bispecific antibody pretargeting is highly specific for imaging micrometastatic disease and may thus provide a complementary method to ¹⁸F-FDG at clinical examination.

© RSNA, 2008

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