AMINOSYN-II EFFECTIVELY BLOCKS RENAL UPTAKE OF F-18 LABELED ANTI-TAC DISULFIDE-STABILIZED FV

Because intact IgG has limitations as a tumor-imaging agent, radiolabe led Fv fragments are being evaluated. Due to the high renal accumulati on of Fv fragments, methods to block renal uptake are being sought. Th is study evaluated how well Aminosyn II, a Food and Drug Administratio n-approved 15% amino acid solution, would block the renal accumulation of F-18 anti-Tac disulfide-stabilized Fv (dsFv) fragments (small frag ments with high renal uptake). The anti-Tac dsFv is directed against t he cu subunit of the interleukin 2 receptor. It was labeled at specifi c activities of 1.1-2.7 mCi/mg using N-succinimidyl 4-[F-18]fluorometh yl benzoate. Four adult baboons a ere injected i.v., with 0.7-1.9 mCi and 150 pg of dsFv. Each baboon was preinjected with Aminosyn II i.v. and, on a separate occasion, with a control solution. Thirty min befor e injection of F-18-labeled anti-Tac dsFv, a bolus of either solution was given, followed by a constant infusion of 13.3 ml/kg/h. Quantitati ve positron emission tomography imaging was performed. The amino acid levels in serum were measured serially. The baseline levels of lysine (and other amino acids) in plasma were not significantly different in either the Aminosyn Za or control infusion group and did not change du ring the control infusion. In the Aminosyn II group, lysine levels in plasma 5 min before anti-Tac dsFv infusion were 5-15 times higher than the baseline value and continued to rise during the infusion. The are as under the curve in blood of the F-18-labeled anti-Tac dsFv, from ti me of injection to end of imaging, expressed as percentage injected do se (%ID), were 28.94 +/- 4.05%ID x h/liter (mean +/- SD) for the contr ol group and 32.09 +/- 11.15%ID x h/liter for the Aminosyn IH group (P = 0.54). The peak concentration of F-18-labeled anti-Tac dsFv in the kidney of the controls was 24.53 +/- 4.34%ID; the value in the Aminosy n II group was 5.39 +/- 1.89%ID, representing a mean decrease of 78.5% . The times to reach 90% of the peak levels of F-18 in the kidney were 5.6 +/- 3.0 min for the Aminosyn II group and 33.8 +/- 4.8 min for th e control group. The amounts excreted in urine by 90 min were 47.7 +/- 8.55%ID and 78.5 +/- 12.8%ID (P = 0.01) for the controls and Aminosyn II group, respectively. In conclusion, Aminosyn Il effectively blocks the renal accumulation of F-18-labeled anti-Tac dsFv. Use of Aminosyn HI should allow much higher tracer administration for the same radiat ion exposure to the target organ (kidney).