Preliminary radiochemical and biological studies on the liposome encapsulated platinum-[125I]iodohistamine complex

BACKGROUND: The platinum-iodohistamine complex with in vitro cytostatic activity toward colon and mammary cancer cells has been synthesised recently in our laboratory. The pharmacokinetics of radioactive complex analogues, labelled with I-131 and I-125, has been examined in murine model of spontaneous mammary adenocarcinoma. The present work is devoted to the examination of the potential use of liposomes as a carrier system for the radioactive platinum-[*I]iodohistamine complex in vivo. MATERIAL AND METHODS: Encapsulations of the Pt- [125I]iodohistamine were studied using a different molar ratio of the complex and liposomes with positive surface charge, as well as various incubation procedures. Biodistribution of the initial and the liposomal form of the complex were studied in C3H tumour-bearing mice with spontaneously developed and transplantable (16C) mammary adenocarcinoma. RESULTS: Comparative biodistribution studies in C3H/16C mice and in mice with spontaneously developed mammary tumour have shown that in the former model pharmacokinetics of the Pt-[125I]iodohistamine complex is more predictable and more similar to that observed for cisplatin. Therefore, the transplantable tumour model is more advantageous for the complex and its liposomal form evaluation. In C3H/16C mice, significant differences in the biodistribution between the radioactive platinum complex and its liposomal form were observed. The concentration of the activity in blood after 2 h p.i.v. was two times lower for the encapsulated complex, and the uptake of the radioactivity by liver, spleen, and lungs was twice as high as that obtained for the free Pt-[125I]iodohistamine preparation. The radioactivity in tumour was almost constant for liposomal platinum complex (ca. 2% ID/g), although it was two times lower compared to the initial platinum complex. CONCLUSIONS: The results of the present study indicate that platinum-[*I]iodohistamine can be efficiently incorporated into cationic liposomes (c. 40%). However, the uptake of the encapsulated complex by the liver and spleen macrophages demands further modification of the lipid membrane

Identification of transplanted pancreatic islet cells by radioactive Dithizone-[131I]-Histamine conjugate. Preliminary report

Background: The unique mechanism of dithizone action in the interior of the viable pancreatic islet suggests the possible development of a specific radiopharmaceutical that may have a potential clinical application in the diagnosis of the pancreatic organ allografts or islets rejection. The radiodiagnostic properties of the newly developed radioactive analogue of dithizone, i.e. Dithizone-[131I]-Histamine conjugate have been evaluated in the present study. METHODS: The four islet cells transplantation models were chosen for this purpose. The most important feature of the Dithizone-[131I]-Histamine conjugate is its possessed ability of zinc chelation. As was presented in the recent study, the conjugate stains pink-reddish the isolated pancreatic islets in vitro. Among the studied transplantation models, only the islets grafting under testis capsule enabled determination of the pancreatic islets in rats by radioactive Dithizone-[131I]-Histamine conjugate. The level of the radioactivity in the recipient testis (right) was almost two times higher compared to the controls (0.24 vs. 0.13% ID/g, respectively). CONCLUSIONS:These preliminary data demonstrate the ability of the developed radioactive analogue of dithizone for in vivo identification of transplanted pancreatic islets, and suggests a potential clinical application of the radiodithizone in the diagnosis of the pancreatic islet rejection