Preclinical safety, biodistribution and dosimetry estimates of 99mTc-DTPA-glipizide as a novel compound imaging pancreatic islet cells

Objectives This study aimed to evaluate the biodistribution, radiation dosimetry, and acute toxicity of ^99mTc-DTPA-glipizide (DTPA-GLP) in rats.

Methods DTPA dianhydride conjugated with GLP in dimethylsulfoxide, yielded 60%. Biodistribution and planar images were obtained at 30-120 min after injection of ^99mTc-DTPA-GLP (1 mg/rat) in healthy female Fischer 344 rats. Acute toxicity was studied with Fischer 344 male and female rats injected intravenously with ^99mTc-DTPA-GLP (3, 10 mg/rat, 11.1 MBq/rat). Toxicity was evaluated by determination of biochemistry parameters. Radiation dosimetry projections in humans were estimated on the basis of the residence times in rats by use of the MIRDose 3.1 software package.

Results Structure of DTPA-GLP was confirmed by NMR, mass spectrometry and HPLC. Radiochemical purity assessed by ITLC was > 96%. ^99mTc-DTPA-GLP showed increased pancreas-to-muscle ratios whereas ^99mTc-DTPA showed decreased ratios at various time-points. Pancreas could be visualized with ^99mTc-DTPA-GLP in normal rat, whereas no uptake in the pancreas was observed in rats pretreated with streptozotocin. Biochemistry results (ALT and AST, bilirubin, BUN, creatinine, and glucose levels) remained within or close to the normal ranges. The projected effective dose equivalent in humans was 0.0113 rem/mCi. Thehighest absorbed doses would be received by the kidney (0.0669 rem/mCi).

Conclusions ^99mTc-DTPA-GLP is safe and feasible to assess pancreas beta cell receptor recognition.