BORONATED PORPHYRINS FOR NEUTRON CAPTURE THERAPY

10B(n, α)7Li反应在中子俘获治疗中的应用

Utilization of the 10B(n,Alpha)7Li reaction for Neutron Capture Therpay (NCT) provides potentially optimal conditions for radiotherapy. Physiological localization of boron in tumor cells permits selective irradiation of cancer cells within the radiation field, as the range of the He and Li ions is about 1 cells diameter (approximately 10M) in tissue. The high relative biological effect from these radiations provides advantages commonly accorded to high LET radiations. Recent work indicates that a number of compounds, including porphyrins, show selective binding to cancer cells in amounts which may enable their uses as vehicles for the transport of boron to tumor. Selectivve binding of the boronated analogs to tumor would allow clearance of boron from normal tissues, thus providing the condition requisite for successful NCT. Endogenous porphyrins (HpD) are already in clinical use for phototherapy, where red light is used to stimulate a cytoxic response in tumors. The evident success, at least with superficial cancers, gives biological evidence of selective concentrations of porphyrins in tumors adequate for therapy. In addition, we have investigated the biodistribution of a synthetic porphyrin (tetraphenylporphinesulfonate, or TPPS) in 7 different animal tumor models. Our data, as well as that of others, indicates abundant accumulations of TPPS in tumor, such that if boronated analogs behave in the same way, boron concentrations in tumors would be up to 10X that needed for therapy. Thus available data indicate that boronated porphyrins may provide the most direct route to adequate boron localization in tumor. Utilization of such porphyrin analogs is similar in concept to phototherapy currently being used clinically, with the distinct advantage of deeper tissue penetration produced by the activating neutrons. The most obvious prime area for clinical testing of clinical testing of porphyrins in neutron capture therapy would be the treatment of brain tumors. Here, the blood-brain barrier would exclude porphyrins from normal brain. Since the treatment volume is limited to the brain, clearance of boronated porphyrins from other normal tissues is not required. We plan to synthesize boronated porphyrins, carry out biodistribution studies in animals, conduct kinetic studies on successful analogs and test these compounds in animals for toxicity in organs indicated by the distribution studies.