Renal uptake and retention of radiolabeled somatostatin, bombesin, neurotensin, minigastrin and CCK analogues: species and gender differences.
BACKGROUND
During therapy with radiolabeled peptides, the kidney is most often the critical organ. Newly developed peptides are evaluated preclinically in different animal models before their application in humans. In this study, the renal retention of several radiolabeled peptides was compared in male and female rats and mice.


METHODS
After intravenous injection of radiolabeled peptides [somatostatin, cholecystokinin (CCK), minigastrin, bombesin and neurotensin analogues], renal uptake was determined in both male and female Lewis rats and C57Bl mice. In addition, ex vivo autoradiography of renal sections was performed to localize accumulated radioactivity.


RESULTS
An equal distribution pattern of renal radioactivity was found for all peptides: high accumulation in the cortex, lower accumulation in the outer medulla and no radioactivity in the inner medulla of the kidneys. In both male rats and mice, an increasing renal uptake was found: [(111)In-DTPA]CCK8<[(111)In-DTPA-Pro(1),Tyr(4)]bombesin approximately [(111)In-DTPA]neurotensin<[(111)In-DTPA]octreotide<<[(111)In-DTPA]MG0. Renal uptake of [(111)In-DTPA]octreotide in rats showed no gender difference, and renal radioactivity was about constant over time. In mice, however, renal uptake in females was significantly higher than that in males and decreased rapidly over time in both genders. Moreover, renal radioactivity in female mice injected with [(111)In-DTPA]octreotide showed a different localization pattern.


CONCLUSIONS
Regarding the renal uptake of different radiolabeled peptides, both species showed the same ranking order. Similar to findings in patients, rats showed comparable and constant renal retention of radioactivity in both genders, in contrast to mice. Therefore, rats appear to be the more favorable species for the study of the renal retention of radioactivity.
Melis
Marleen
M
Department of Nuclear Medicine, Erasmus MC Rotterdam, 3015 CE Rotterdam, The Netherlands. m.melis@erasmusmc.nl
Krenning
Eric P
EP
Bernard
Bert F
BF
de Visser
Monique
M
Rolleman
Edgar
E
de Jong
Marion
M
D000818:Animals; D001345:Autoradiography; D001839:Bombesin / Q000493:pharmacokinetics*; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005260:Female; D005755:Gastrins / Q000493:pharmacokinetics*; D006727:Hormone Antagonists / Q000493:pharmacokinetics*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007205:Indium Radioisotopes; D007553:Isotope Labeling; D007668:Kidney / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009496:Neurotensin / Q000493:pharmacokinetics*; D004369:Pentetic Acid / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats; D011917:Rats, Inbred Lew; D012727:Sex Characteristics; D013004:Somatostatin / Q000493:pharmacokinetics*; D013045:Species Specificity; D014018:Tissue Distribution
D005755:Gastrins; D006727:Hormone Antagonists; D007205:Indium Radioisotopes; C008530:minigastrin; D009496:Neurotensin; D013004:Somatostatin; D004369:Pentetic Acid; D002766:Cholecystokinin; D001839:Bombesin