CONTROLLED USE OF POLYETHER-SUBSTITUTED TUMOR AGENTS IN DIAGNOSIS AND THERAPY

摘要

Tumour active or tumour diagnostic compound (I), which concentrates in the tumour, is coupled to a compound (II), with at least two phenolic OH groups or at least one aliphatic amino group, where at least 2 OH or at least 1 NH2 groups are substituted with a polyethylene glycol chain whose polymerisation degree, n, is 5-250, and whose terminal OH group is substituted with a 1-12C alkyl ester or ether. Preferably n = 10-200 (100-110) and (I) is a cis-platin compound, tetracycline, steroid, porphin, phthalocyanine or a conventional X-ray contrast agent. (I) is formed by reacting (II) with the polyethylene glycol ester or ether (III) in solution. When (III) has a molecular weight of more than 5000 (especially more than 10,000) it is activated with cyanuric chloride. - (I) may be radio-labelled, especially as Gd-phthalocyanine metal complexes, Dy164 derivatives of e.g. phthalocyanine or radiolabelled diphosphonates for radiotherapy with L131 or L125, or are conjugated to give radio-iodo, radio-bromo or radio-metal ion activated peptides, porphins or phthalocyanines. Highly iodo-substituted compounds especially porphins and tyrosine oligomers, and boric acid esters, luminols, and radiosensitisers especially nitroimidazoles, in the form of polyethylene glycol derivatives, are also claimed.