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


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.


CONCLUSIONS
Bispecific antibody pretargeting is highly specific for imaging micrometastatic disease and may thus provide a complementary method to (18)F-FDG at clinical examination.
Sharkey
Robert M
RM
Center for Molecular Medicine and Immunology, Garden State Cancer Center, 520 Belleville Ave, Belleville, NJ 07109, USA. rmsharkey@gscancer.org
Karacay
Habibe
H
Vallabhajosula
Shankar
S
McBride
William J
WJ
Rossi
Edmund A
EA
Chang
Chien-Hsing
CH
Goldsmith
Stanley J
SJ
Goldenberg
David M
DM
D000818:Animals; D000911:Antibodies, Monoclonal; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D007089:Image Enhancement / Q000379:methods; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D012680:Sensitivity and Specificity; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D000911:Antibodies, Monoclonal; D019275:Radiopharmaceuticals