D-lysine reduction of indium-111 octreotide and yttrium-90 octreotide renal uptake

Indium-111-DTPA-octreotide (111In-DTPAOC) is used successfully for imaging somatostatin receptor-positive lesions. A new and promising application is its use in peptide-receptor radionuclide therapy (PRRT). For the latter purpose, [DOTA0,D-Phe1,Tyr3]octreotide (DOTATOC), which is suitable for stable radiolabeling with 90Y, is probably even more promising. Significant renal uptake of these octreotide analogs exists, however, reducing the scintigraphic sensitivity for detection of small tumors in the perirenal region and limiting the possibilities for PRRT. We showed that the renal uptake of 111In-DTPAOC could be reduced to about 50% of control by L-lysine administration in vivo in rats. This study compares the effects of several doses and different methods of administration of D- and L-lysine, in addition to time-related effects of D-lysine, on kidney uptake of 111In-DTPAOC and 90Y-DOTATOC.

Male Wistar rats (200-250 g) were given 111In-DTPAOC (0.2 MBq, 0.5 microg-0.5 mg intravenously, intraperitoneally or orally) in the presence or absence of D- or L-lysine. At 1, 4 or 24 hr, the rats were killed, and the organs were isolated and counted for radioactivity. In different experiments, male Wistar rats (200-250 g) were given 90Y-DOTATOC (1 MBq, 0.5 microg intravenously) in the presence or absence of D-lysine. At 24 hr, the rats were killed, and the organs were isolated and counted for radioactivity.

Administration of D- or L-lysine in a single intravenous dose of 400 mg/kg, resulted in more than 50% inhibition of kidney uptake of 111In-DTPAOC at all time points tested, independently of the mass of 111In-DTPAOC used. Higher or repeated doses of lysine did not give a significantly higher percentage inhibition. D-lysine, given orally in a dose of 400 mg/kg at 30 or 15 min before 111In-DTPAOC injection, resulted in 30% and 20% inhibition of kidney uptake, respectively. L-lysine, given orally 30 min before 111In-DTPAOC administration, resulted in 30% inhibition as well. Inhibition of kidney uptake of 111In-DTPAOC by L-lysine after intraperitoneal administration was 40%. After L-lysine administration, 111In-DTPAOC was decreased in the kidneys and in somatostatin receptor-positive organs such as the pancreas and adrenal glands. In contrast, D-lysine did not have a significant effect on uptake in octreotide receptor-positive organs. Renal uptake of 90Y-DOTATOC was reduced by 65% by intravenous D-lysine, whereas radioactivity in blood, pancreas and adrenal glands was not affected.

D-lysine may be preferred to L-lysine for reduction of renal uptake of radioactivity during scintigraphy and PRRT because of its lower toxicity and because it should not interfere with the natural amino acid metabolic balance.