Megalin Is Essential for Renal Proximal Tubule

Radiolabeled somatostatin analogs have been shown to be important radiopharmaceuticals for tumor diagnosis and radionuclide therapy. The kidney has appeared to be the critical organ during radionuclide therapybecauseof peptide reabsorption and retention in theproximal tubules after glomerular filtration. The molecular mechanism of renal reabsorption of these analogs has not been clarified. A possible receptor candidate ismegalin, amultiligand scavenger receptor in the renal proximal tubules. The objective of this study was to investigate the role of megalin in tubular reabsorption of radiolabeled somatosta-tin analogs by using kidney-specific megalin-deficient mice versus mice with normal renal megalin expression. [111In-Diethylenetriamine-pentaacetic acid (DTPA)]octreotide was used as a practical model of peptide. Methods: Renal uptake of [111In-DTPA]octreotide was de-termined by animal SPECT scintigraphy at different time points after injection of the tracer and by measurement of radioactivity after iso