Amino acid infusion blocks renal tubular uptake of an indium-labelled somatostatin analogue

Abstract

Summary The Indium-labelled somatostatin analogue pentetreotide has been successfully developed for imaging of somatostatin receptor positive tumours. However there is significant renal tubular uptake of the radiolabelled peptide, which can obscure upper abdominal tumours and would preclude its use for targeted radiotherapy. The aim of this study was to determine whether amino acid infusion, which has been shown to block renal tubular peptide reabsorption, diminishes renal parenchymal uptake of this radiolabelled analogue.Eight patients being scanned with the "'In-labelled somatostatin analogue, pentetreotide, for localisation of gastroenteropancreatic tumours received an infusion of synthetic amino acids. The ratio of isotope uptake in kidney to that in spleen was assessed, and compared to the ratio for matched control patients, to determine if amino acid infusion reduced renal parenchymal uptake of the radiopharmaceutical. The amount of isotope in the urine was determined to ensure that any effect of the amino acid infusion was unrelated to changes in clearance.Infusion of amino acids significantly reduced renal parenchymal uptake of isotope at 4 h. There was a non-significant increase in urinary clearance of isotope over the 4 h, consistent with reduced reuptake and a lack of effect on glomerular filtration rate.This technique, by preventing renal damage, may allow the use of this somatostatin analogue for local radiotherapy, and could be of wider value in blocking tubular re-uptake of potentially nephrotoxic agents, such as radiolabelled Fab fragments.

Indication for Different Mechanisms of Kidney Uptake of Radiolabeled Peptides

“…For OCT as a radiolabeled peptide, this effect was demonstrated in the early 1990s (13). It is assumed that uptake of OCT occurs in the proximal tubule cells in the kidneys.…”

Renal Toxicity of Radiolabeled Peptides and Antibody Fragments: Mechanisms, Impact on Radionuclide Therapy, and Strategies for Prevention

“…Several years later, coadministration of the basic amino acids lysine and arginine was found to reduce the renal uptake of radiolabeled antibody fragments and somatostatin analogs (61,62). Behr et al reported that poly-L-lysine was more potent than L-lysine or D-lysine in reducing the renal retention of radiolabeled Fab9 fragments in rats, but poly-L-lysine was also more toxic.…”

Somatostatin receptor subtype 2-mediated uptake of radiolabelled somatostatin analogues in the human kidney

“…It was recently shown that renal uptake of somatostatin analogues can be inhibited by maleic acid, which interferes with cellular energy supplies [10], by colchicine [11] due to dysfunction of proximal tubule reabsorption processes and by positively charged amino acids such as lysine and arginine [10,12,13]. Based on animal studies and clinical data [6,[14][15][16][17], PRRT is nowadays performed by coinfusion of lysine and arginine for kidney protection.…”