Reducing renal uptake of radiolabeled peptides using albumin fragments.

نویسندگان

  • Erik Vegt
  • Julliëtte E M van Eerd
  • Annemarie Eek
  • Wim J G Oyen
  • Jack F M Wetzels
  • Marion de Jong
  • Frans G M Russel
  • Rosalinde Masereeuw
  • Martin Gotthardt
  • Otto C Boerman
چکیده

UNLABELLED In most types of peptide receptor radionuclide therapy, the maximum activity dose that can be administered is limited by high and persistent renal retention of the radiolabeled peptides, which is, at least partly, mediated by the megalin receptor. Several agents that interfere with renal reabsorption of radiolabeled peptides have been identified (e.g., lysine, arginine, succinylated gelatin solution), but none of these inhibit renal reabsorption completely. Albumin, a naturally abundant megalin ligand, might be a safe and potent alternative. In this study, we analyzed the effects of albumin and fragments of albumin (FRALB) on the renal reabsorption of (111)In-diethylenetriaminepentaacetic acid (DTPA)-d-Phe(1)-octreotide ((111)In-octreotide), [Lys(40)(aminohexoic acid-DTPA-(111)In)NH(2)]-exendin-4 ((111)In-exendin), and (111)In-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-Glu(1)-minigastrin ((111)In-minigastrin). METHODS The effects of albumin and FRALB on megalin-associated binding of (111)In-octreotide, (111)In-exendin, and (111)In-minigastrin were assessed in vitro using rat yolk sac epithelial (BN16) cells. In vivo, uptake and localization of (111)In-albumin and (111)In-FRALB in the kidneys of Wistar rats were determined, as well as the effect of lysine, succinylated gelatin solution, albumin, and FRALB on the kidney uptake of (111)In-octreotide, (111)In-exendin, and (111)In-minigastrin. RESULTS FRALB significantly reduced binding and uptake of (111)In-octreotide, (111)In-exendin, and (111)In-minigastrin by BN16 cells. In rats, renal uptake of (111)In-labeled FRALB was significantly higher than that of (111)In-labeled intact albumin (P<0.001). FRALB administration effectively reduced renal uptake of (111)In-octreotide, (111)In-exendin, and (111)In-minigastrin. Administration of 1-2 mg of FRALB reduced renal uptake of (111)In-octreotide as efficiently as 80 mg of lysine. CONCLUSION Renal uptake of (111)In-octreotide and other radiolabeled peptides in rats can be effectively reduced by administration of albumin fragments. Additional studies to identify the albumin fragments responsible for inhibition of renal peptide uptake are warranted.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Chemical design of radiolabeled antibody fragments for low renal radioactivity levels.

The renal uptake of radiolabeled antibody fragments presents a problem in targeted imaging and therapy. We hypothesized that the renal radioactivity levels of radiolabeled antibody fragments could be reduced if radiolabeled compounds of urinary excretion were released from glomerularly filtered antibody fragments before they were incorporated into renal cells by the action of brush border enzym...

متن کامل

Physiologically Based Pharmacokinetic (PBPK) model for biodistribution of radiolabeled peptides in patients with neuroendocrine tumours

Objective(s): The objectives of this work was to assess the benefits of the application of Physiologically Based Pharmacokinetic (PBPK) models in patients with different neuroendocrine tumours (NET) who were treatedwith Lu-177 DOTATATE. The model utilises clinical data on biodistribution of radiolabeled peptides (RLPs) obtained by whole body scintigraphy (WBS) of the patients.Methods: The blood...

متن کامل

Inhibition of the Metabolic Degradation of Filtered Albumin Is a Major Determinant of Albuminuria

Inhibition of the degradation of filtered albumin has been proposed as a widespread, benign form of albuminuria. There have however been recent reports that radiolabeled albumin fragments in urine are not exclusively generated by the kidney and that in albuminuric states albumin fragment excretion is not inhibited. In order to resolve this controversy we have examined the fate of various radiol...

متن کامل

Indication for different mechanisms of kidney uptake of radiolabeled peptides.

UNLABELLED Nephrotoxicity due to renal reabsorption of radiolabeled peptides limits the tumor dose in peptide receptor radiotherapy (PRRT). Therefore, we evaluated the ability of several agents to inhibit the renal accumulation of different radiopeptides. METHODS Male Wistar rats (4 per group) were injected intravenously with 1 MBq of (111)In-labeled octreotide (OCT), minigastrin (MG), bombes...

متن کامل

Selection of radiolabeled gastrin analogs for peptide receptor-targeted radionuclide therapy.

UNLABELLED The gastrin/cholecystokinin-2 (CCK-2) receptor has been identified as a possible target for peptide receptor radionuclide imaging and therapy. Several radiolabeled peptides binding to this receptor have been explored in animal models and clinical trials but either low tumor uptake or high renal retention has been found. The aim of this study was to identify a peptide with improved tu...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of nuclear medicine : official publication, Society of Nuclear Medicine

دوره 49 9  شماره 

صفحات  -

تاریخ انتشار 2008