Gelatin-based plasma expander effectively reduces renal uptake of 111In-octreotide in mice and rats.
111In-Diethylenetriaminepentaacetic acid-octreotide generally is used for the scintigraphic imaging of neuroendocrine and other somatostatin receptor-positive tumors. On the basis of the successful targeting of octreotide, radiolabeled somatostatin analogs, such as 90Y-(1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid [DOTA])0-Tyr3-octreotide and 177Lu-DOTA0-Tyr3-octreotate, were developed for peptide receptor radionuclide therapy. However, the maximum tolerated doses of these analogs are limited because of the high and persistent renal uptake that leads to relatively high radiation doses in the kidneys. Renal uptake can be reduced by coinfusion of basic amino acids or polypeptides. However, high doses of basic amino acids can induce severe side effects. It was reported that the infusion of gelatin-based plasma expanders resulted in increased low-molecular-weight proteinuria, suggesting that these plasma expanders interfere with the tubular reabsorption of peptides and proteins. In the present study, we analyzed the effects of several plasma expanders on the renal uptake of 111In-octreotide in rats and mice.


METHODS
Wistar rats and BALB/c mice were injected with 0.5 or 0.1 mL of plasma expander, respectively. Thereafter, the animals received 111In-octreotide intravenously. Animals were killed at 20 h after the injection of the radiopharmaceutical. Organs were dissected, and the amount of radioactivity in the organs and tissues was measured.


RESULTS
The administration of 20 mg of Gelofusine in rats or 4 mg in mice was as effective in reducing the renal uptake of 111In-octreotide as the administration of 80 or 20 mg of lysine in rats or mice, respectively, without reducing 111In-octreotide uptake in receptor-positive organs. Plasma expanders based on starch or dextran had no effect on the renal uptake of 111In-octreotide.


CONCLUSIONS
The gelatin-based plasma expander Gelofusine significantly reduced the kidney uptake of 111In-octreotide as effectively as did lysine. Because Gelofusine is a well-known and generally used blood volume substitute that can be applied safely without the induction of toxicity, evaluation of this compound for its potential to reduce the kidney uptake of radiolabeled peptides in patients is warranted.
van Eerd
Julliëtte E M
JE
Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. j.vaneerd@nucmed.umcn.nl
Vegt
Erik
E
Wetzels
Jack F M
JF
Russel
Frans G M
FG
Masereeuw
Rosalinde
R
Corstens
Frans H M
FH
Oyen
Wim J G
WJ
Boerman
Otto C
OC
D000818:Animals; D001822:Body Burden; D004338:Drug Combinations; D005260:Female; D005780:Gelatin / Q000008:administration & dosage* / Q000627:therapeutic use*; D007668:Kidney / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009928:Organ Specificity; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013386:Succinates / Q000008:administration & dosage* / Q000627:therapeutic use*
D004338:Drug Combinations; D011837:Radiation-Protective Agents; D019275:Radiopharmaceuticals; D013386:Succinates; C094279:indium-111-octreotide; C060085:succinylated gelatin; D005780:Gelatin; D015282:Octreotide