Renal imaging via receptor-mediated binding of radiolabeled tilmanocept to mesangial cells of healthy rats
JOURNAL OF NUCLEAR MEDICINE(2014)
摘要
384 Objectives There is an unmet need for imaging specific sites of inflammation and fibrosis in the kidney. Glomerular mesangial cells reside behind a fenestrated endothelial barrier and form the central stalk of the glomerulus. They regulate glomerular blood flow, as well as provide structural support and immune surveillance of invading pathogens. This latter function is consistent with the role of CD206, the receptor for [99mTc]tilmanocept (FDA approval 2013). The objective of this study is to determine if glomerular mesangial cells are the site of renal accumulation of tilmanocept. Methods Three rats were injected (iv) with IRDye800-labeled [68Ga]tilmanocept (0.10 nmol/g, 0.1 - 0.3 mCi). After 20 mins of PET imaging (Vista DR) over the kidneys and a 5-min static image over the bladder, each rat was euthanized and frozen sections of both kidneys were immunofluorescently stained for podocytes (Alexa-488), and CD206 (Alexa-647). Renal time-SUV curves were generated and the time to reach 90 percent of the peak value (T90) was calculated. Results Time-SUV curves demonstrated accumulation within the renal cortex with plateau SUVs ranging from 11 to 19 (median = 13.7). The T90 values ranged from 3.2 to 7.9 min (median = 4.25 min). The cortical activity was retained for 25 mins with no evidence of filtration; absent renal pelvis or urinary bladder activity. Histologic examination demonstrated co-localization of CD206 and fluorescent-labeled tilmanocept within glomerular compartments in a mesangial-type distribution. Conclusions This study demonstrated mesangial cell accumulation of tilmanocept. Given the significant role of mesangial cells during the development of fibrotic, inflammatory, and diabetic nephropathies, SPECT or PET renal imaging with radiolabeled tilmanocept may offer a novel receptor-based imaging biomarker to monitor the progression of glomerular disease. Research Support P50 CA114745
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