Differential inhibitory effect of L‐lysine on renal accumulation of 67 Cu‐labelled F(ab′) 2 fragments in mice

The basic amino acid L‐lysine was administered to mice in an attempt to circumvent unwanted renal accumulation of 67 Cu‐labelled F(ab′) 2 fragments derived from the anti‐NCAM IgG 1 , SEN7 and anti‐CEA IgG 1 monoclonal antibody (MAb)35. In control experiments, significant renal uptake of both 67 Cu‐labelled F(ab′) 2 fragments was observed, radiolabel being primarily localised to proximal tubules in the renal cortex. Following optimised L‐lysine dosing protocols, renal uptake of 67 Cu‐MAb35 F(ab′) 2 was inhibited by up to 42%. Surprisingly, little inhibition (<10%) of 67 Cu‐SEN7 F(ab′) 2 uptake was observed. Experiments to investigate this differential inhibition indicated that inhibition of MAb35 F(ab′) 2 uptake was relatively short‐lived (approx. 6 hr), whilst no apparent differences were found in blood clearance rates between either 67 Cu‐F(ab′) 2 fragment. L‐lysine administration caused a significant diuresis with high levels of intact 67 Cu‐labelled SEN7 and MAb35 F(ab′) 2 appearing in the urine, possibly due to blockade of renal uptake and lysine‐induced increases in glomerular membrane permeability. Iso‐electric focusing studies failed to identify any charge differences between the 67 Cu‐labelled F(ab′) 2 fragments, although a cathodal migration of all 67 Cu‐labelled samples, presumably due to the net positive charge conferred by addition of 67 Cu 2+ ions, was observed. Our results demonstrate that in addition to net charge, other unidentified characteristics may influence renal accumulation of radiometal‐labelled F(ab′) 2 fragments and their inhibition by L‐lysine. Int. J. Cancer 72:522–529, 1997. © 1997 Wiley‐Liss, Inc.