Fiedor P S, Oluwole S F, Hardy M A
Department of Surgery, College of Physicians and Surgeons of Columbia University, 630 West 168 Street, New York, New York 10032, U.S.A.
World J Surg. 1996 Oct;20(8):1016-22; discussion 1022-3. doi: 10.1007/s002689900155.
Transplantation of whole pancreas or pancreatic islets remains a promising approach to treatment of diabetes mellitus. Because at present there is no efficient method for in vivo early diagnosis of pancreatic islet rejection or for disorders of pancreatic endocrine function, we examined if dithizone (DTZ) and a synthetic iodo-derivative of DTZ (I-DTZ) can be used as a potential radioactive marker for monitoring viable transplanted pancreatic islets. Human pancreatic islets harvested from multiorgan donors were tested ex vivo after intraductal injection of DTZ solution for islet staining. Lewis rats were used in the in vivo experiments for localizing pancreatic islets in situ after intravenous injection of various concentrations of DTZ or I-DTZ. Fresh rat islets were transplanted into streptozotocin-induced diabetic recipients, either underneath the kidney capsule or intraperitoneally. Intravenous DTZ or I-DTZ was then used for macroscopic and microscopic identification of viable transplanted islets. These studies indicate that DTZ and I-DTZ solutions specifically stain pancreatic islets in vivo after intravenous injection without damage to their endocrine function as assessed by plasma insulin and glucose levels. Human islets stain red in in vitro studies similar to the DTZ (I-DTZ) effect in rats. We conclude that DTZ and I-DTZ are effective in the in vivo and in vitro identification of pancreatic islets and may have potential clinical application in the detection of pancreatic islet tumors (insulinomas) and in the diagnosis of rejection of pancreatic organ allografts or islets.
全胰腺或胰岛移植仍然是治疗糖尿病的一种有前景的方法。由于目前尚无用于胰岛排斥反应的体内早期诊断或胰腺内分泌功能紊乱的有效方法,我们研究了双硫腙(DTZ)及其合成碘衍生物(I-DTZ)是否可作为监测存活移植胰岛的潜在放射性标记物。将从多器官供体获取的人胰岛在导管内注射DTZ溶液进行胰岛染色后进行体外测试。在体内实验中,给Lewis大鼠静脉注射不同浓度的DTZ或I-DTZ后,对胰腺胰岛进行原位定位。将新鲜的大鼠胰岛移植到链脲佐菌素诱导的糖尿病受体的肾包膜下或腹腔内。然后静脉注射DTZ或I-DTZ用于对存活的移植胰岛进行宏观和微观鉴定。这些研究表明,静脉注射后,DTZ和I-DTZ溶液可在体内特异性地对胰岛进行染色,且根据血浆胰岛素和葡萄糖水平评估,不会损害其内分泌功能。在体外研究中,人胰岛染成红色,类似于DTZ(I-DTZ)在大鼠中的作用。我们得出结论,DTZ和I-DTZ在体内和体外对胰岛的鉴定中均有效,并且在胰岛肿瘤(胰岛素瘤)的检测以及胰腺器官同种异体移植或胰岛排斥反应的诊断中可能具有潜在的临床应用价值。