SI(IV)-METHOXYETHYLENE-GLYCOL-NAPHTHALOCYANINE - SYNTHESIS AND PHARMACOKINETIC AND PHOTOSENSITIZING PROPERTIES IN DIFFERENT TUMOR-MODELS

A Si(IV)-naphthalocyanine bearing two methoxyethylenglycol axial ligan ds to the centrally coordinated metal ion (SiNc) was prepared by chemi cal synthesis and assayed for the phototherapeutic activity after admi nistration in a Cremophor formulation to C57BI/6 mice bearing a subcut aneously transplanted Lewis lung carcinoma or B16 pigmented melanoma. Pharmacokinetic studies indicate that the maximal accumulation in the tumour occurs at 24 h after intraperitoneal injection of 0.5 mg kg(-1) of SiNc, although the naphthalocyanine concentration in the Lewis lun g carcinoma (0.70 mu g g(-1)) is significantly larger than that in the B16 pigmented melanoma (0.15 mu g g(-1)). This results in a higher se lectivity of tumour targeting in the case of the lung carcinoma. Fhoto dynamic therapy (782 nm, 370 mW cm(-2), 360 J cm(-2)) at 24 h after Si Nc injection causes an efficient tumour response for Lewis lung carcin oma (50% lower tumour diameter on day 19 post-treatment as compared to untreated controls) while the pigmented melanoma shows only a minor r esponse regarding the rate of tumour growth. (C) 1997 Elsevier Science S.A.