Metastatic human colonic carcinoma: molecular imaging with pretargeted SPECT and PET in a mouse model.

Abstract

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 ((18)F) 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 (18)F-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 (18)F-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 (18)F-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 (18)F-FDG at clinical examination.

• Authors: Robert M Sharkey, Habibe Karacay, Shankar Vallabhajosula, William J McBride, Edmund A Rossi, Chien-Hsing Chang, Stanley J Goldsmith, David M Goldenberg
• Journal: Radiology (Radiology) Vol. 246 Issue 2 Pg. 497-507 (Feb 2008) ISSN: 1527-1315 [Electronic] United States
• PMID: 18227543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) RSNA, 2008.

Chemical References

• Antibodies, Monoclonal
• Radiopharmaceuticals

Topics

• Animals
• Antibodies, Monoclonal
• Colonic Neoplasms (diagnostic imaging)
• Disease Models, Animal
• Drug Delivery Systems (methods)
• Female
• Image Enhancement (methods)
• Lung Neoplasms (diagnostic imaging, secondary)
• Mice
• Mice, Nude
• Positron-Emission Tomography (methods)
• Radiopharmaceuticals
• Sensitivity and Specificity
• Tomography, Emission-Computed, Single-Photon (methods)