For the therapy of solid tumors, co-administration of angiotensin II (AngII) results in an increased uptake of drugs into the tumor interstitium. We have engineered a dimeric sc(FV)(2)-AngII fusion construct that combines the superior kinetics of covalent dimeric scFvs [sc(Fv)(2)], recognizing the pancarcinoma tumor-associated antigen 72 (TAG-72), with the advantageous intrinsic activity of AngII. The binding characteristics of the fusion construct were unaltered by the addition of the AngII sequence [affinity constant K-A 1.18 x 10(7) and 8.42 x 10(6) M-1 for sc(Fv)(2) and sc(Fv)(2)-AngII, respectively]. The binding of the fusion construct to the angiotensin receptor (AT(1)) was similar to AngII, and the arterial contraction was 16 +/- 1% of the response observed with norepinephrine. In animal studies, the radiolabeled sc(Fv)(2)-AngII construct exhibited similar uptake and a more homogeneous distribution within the tumor as compared to sc(FV)(2). (C) 2005 Elsevier Inc. All rights reserved.