Metal complexes of bleomycin: evaluation of [Rh-105]-bleomycin for use in targeted radiotherapy.

Bleomycin has been used as a carrier for several radioisotopes; however, its potential for clinical use has been limited either by the in vivo stability of the complexes or the half-life of the isotope used. The chemical, biological, and radiological properties of 105Rhodium appear to make it an ideal choice for targeted radiotherapy. The synthesis and purification of a hereto unreported 105Rhodium-bleomycin (105Rh-BLM) complex is described.

Biodistribution of model 105Rh-labeled tetradentate thiamacrocycles in rats.

105Rh(III)Cl2 complexes with a limited series of [14]ane- and [16]ane- thia macrocycles were prepared and their biodistributions in Sprague-Dawley rats studied. These studies demonstrate that modifications in the structure and composition of the 105Rh-thia macrocycle complexes produce significant differences in their uptake and retention in both the liver and kidneys. The results indicate that the cis-Rh(III)Cl2-[14]ane thiamacrocycles exhibit less kidney retention than the corresponding trans-Rh(III)Cl2-[16]ane thiamacrocycles.

Studies on the Oral Anticancer Drug JM-216: Synthesis and Characterization of Isomers and Related Complexes.

The complex cis,trans,cis-[PtCl(2)(OAc)(2)NH(3)(c-C(6)H(11)NH(2))] (JM-216) is currently undergoing clinical evaluation as an antitumor agent. In support of characterization and analysis of this complex a study of its isomers and other complexes [PtCl(m)()(OAc)((4)(-)(m)()())NH(3)(c-C(6)H(11)NH(2))] (m = 0-4) has been undertaken. The complexes have been obtained by a variety of synthetic routes which now extend the scope for the preparation of platinum(IV) antitumor complexes.

Evaluation of novel ammine/amine platinum (IV) dicarboxylates in L1210 murine leukaemia cells sensitive and resistant to cisplatin, tetraplatin or carboplatin.

Seventeen alkylamine ammine dicarboxylatodichloroplatinum(IV) complexes of general structure c,t,c-[PtCl2(OCOR1)2NH3(RNH2)], where R = aliphatic or alicyclic and R1 = aliphatic or aromatic, have been evaluated against L1210 cell lines with acquired resistance to cisplatin (10-fold), tetraplatin (34-fold) or carboplatin (14-fold) using an in vitro growth-delay assay. All of these compounds overcame cisplatin, tetraplatin and carboplatin resistance. Potency increased as the number of carbon atoms in the axial aliphatic ligands (R1) increased, for example comparing JM216 (R = cyclohexyl, R1 = CH3, IC50 = 1.