Radiolabeled anti-
carcinoembryonic antigen (CEA)
antibodies have the potential to give excellent images of a wide variety of human
tumors, including
tumors of the colon, breast, lung, and medullar thyroid. In order to realize the goals of routine and repetitive clinical imaging with anti-CEA
antibodies, it is necessary that the
antibodies have a high affinity for CEA, low cross reactivity and uptake in normal tissues, and low immunogenicity. The humanized anti-CEA antibody hT84.66-M5A (M5A) fulfills these criteria with an affinity constant of >10 (10) M (-1), no reactivity with CEA cross-reacting
antigens found in normal tissues, and >90% human
protein sequence. A further requirement for routine clinical use of radiolabeled
antibodies is a versatile method of radiolabeling that allows the use of multiple
radionuclides that differ in their radioemissions and half-lives. We describe a versatile bifunctional
chelator,
DO3A-VS (1,4,7-tris(carboxymethyl)-10-(vinylsulfone)-1,4,7,10-tetraazacyclododecane) that binds a range of radiometals including 111 In for gamma-ray imaging and 64Cu for positron emission tomography (PET), and which can be conjugated with negligible loss of immunoreactivity either to sulfhydryls (SH) in the hinge region of lightly reduced
immunoglobulins or surface lysines (NH) of
immunoglobulins. Based on our correlative studies comparing the kinetics of radiolabeled anti-CEA
antibodies in murine models with those in man, we predict that 64Cu-labeled intact,
humanized antibodies can be used to image CEA positive
tumors in the clinic.