Numerical selection of optimal tumor imaging agents with application to engineered antibodies

Three analytic indicators were used to compare five members of a monoclonal antibody (Mab) family. The cognates consisted of the genetically engineere d intact chimeric IgG(1) (cT84.66) and related engineered fragments [scFv, diabody, minibody, F(ab')(2)] reactive against the same epitope of carcinoe mbryonic antigen (CEA). All analyses were based on radioiodinated Mabs targ eting to colorectal xenografts of LS174T tumors in nude mice. Affinity cons tants were evaluated initially. A second indicator was the imaging figure o f merit (IFOM) which determines how rapidly a statistically significant tum or image can be acquired. Finally, deconvolution was used to determine turn er temporal response to an arterial bolus. This last analysis gave the poss ible tumor accumulation in the absence of normal tissue sequestration. Affi nities were all in excess of 10(8) M-1 and were highest for the divalent Ma bs. Using the IFOM criterion, an I-131 label was best suited as a radiolabe l for the intact (IgG) T84.66, while an I-123 label indicated optimal imagi ng with either minibody or F(ab')(2). Deconvolution analyses showed that di valent members behaved similarly while the univalent member (scFv) had a tu mor residence time smaller by an order of magnitude. The diabody had the la rgest impulse response function, but renal uptake may limit its present use fulness.