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Aminosyn II Effectively Blocks Renal Uptake of ¹⁸F-labeled Anti-Tac Disulfide-stabilized Fv

Department of Nuclear Medicine [J. A. C., M. W.] and Positron Emission Tomography Department [L. L., P. H., W. C. E.], Warren G. Magnuson Clinical Center, and Laboratory of Molecular Biology, Division of Basic Sciences [Q. W., I. P.], National Cancer Institute, NIH, Bethesda, Maryland 20892-1180

Because intact IgG has limitations as a tumor-imaging agent, radiolabeled Fv fragments are being evaluated. Due to the high renal accumulation of Fv fragments, methods to block renal uptake are being sought. This study evaluated how well Aminosyn II, a Food and Drug Administration-approved 15% amino acid solution, would block the renal accumulation of ¹⁸F anti-Tac disulfide-stabilized Fv (dsFv) fragments (small fragments with high renal uptake). The anti-Tac dsFv is directed against the subunit of the interleukin 2 receptor. It was labeled at specific activities of 1.1–2.7 mCi/mg using N-succinimidyl 4-[¹⁸F]fluoromethyl benzoate. Four adult baboons were injected i.v. with 0.7–1.9 mCi and 150 µg of dsFv. Each baboon was preinjected with Aminosyn II i.v. and, on a separate occasion, with a control solution. Thirty min before injection of ¹⁸F-labeled anti-Tac dsFv, a bolus of either solution was given, followed by a constant infusion of 13.3 ml/kg/h. Quantitative 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 II or control infusion group and did not change during 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 areas under the curve in blood of the ¹⁸F-labeled anti-Tac dsFv, from time of injection to end of imaging, expressed as percentage injected dose (%ID), were 28.94 ± 4.05%ID x h/liter (mean ± SD) for the control group and 32.09 ± 11.15%ID x h/liter for the Aminosyn II group (P = 0.54). The peak concentration of ¹⁸F-labeled anti-Tac dsFv in the kidney of the controls was 24.53 ± 4.34%ID; the value in the Aminosyn 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 ¹⁸F in the kidney were 5.6 ± 3.0 min for the Aminosyn II group and 33.8 ± 4.8 min for the 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 II effectively blocks the renal accumulation of ¹⁸F-labeled anti-Tac dsFv. Use of Aminosyn II should allow much higher tracer administration for the same radiation exposure to the target organ (kidney).

¹ To whom requests for reprints should be addressed, at Building 10, Room 1C496, NIH, 10 Center Drive, Bethesda, MD, 20892-1180

Received 12/29/97. Accepted 4/17/98.