The survival identification of pancreatic islets of Langerhans. In vitro and in vivo effects of two dithizone preparations on staining of rat and human islets of Langerhans-preliminary study (Part I).

ABSTRACT

Dithizone (DTZ) which selectively stains islets of Langerhans in vitro has a diagnostic potential in the in vivo identification of viable transplanted pancreatic islets. In the present study, we compared the use of DTZ, and a synthetic iodo-derivative of DTZ (I-DTZ) as a potential radioactive marker for identification of viable transplanted pancreatic islet cells. Fresh islets isolated from Lewis rat donors were transplanted beneath the kidney capsule into each diabetic syngeneic (Lewis) recipient rat. DTZ(I-DTZ) solution was injected intravenously (i.v.) at a dose 10 mg/kg body weight (b.w.) for macro and microscopic identification of surviving transplanted islets. The recipients were nephrectomized to confirm that the normoglycemic state was maintained by the islet grafts. In addition, we administered i.v. at the same time concentrations of DTZ (I-DTZ) to test for toxicity. The results show that following i.v. or intraductal (i.d.) injection of low concentrations does not damage pancreatic islet function as determined by insulin secretion or glucose levels. Angiogenesis and microvascularization were observed for 10-12 days after transplantation, and the histologic and biochemical studies showed no pathological changes in injected rats in organ examined. The human pancreatic islets harvested from multiorgan donors stain red ex vivo in the same way as DTZ or I-DTZ administered i.v. in rats. The results indicate that DTZ has a diagnostic potential in monitoring the survival of transplanted pancreatic islets and possibly in the early diagnosis by radioisotopic detection of pancreatic endocrine diseases.