Studies towards elucidating the potential of 5,10,15,20-tetrakis(p-carboxy-methyleneoxyphenyl)porphyrin as a theranostic agent for applications in PET and PDT

Abstract

Porphyrins, owing to their inherent tendency to accumulate in tumorous lesions, are considered suitable for developing agents for theranostic applications involving tumor diagnosis and targeted tumor therapy. The aim of the present work is to study the potential of a porphyrin derivative namely, 5,10,15,20-tetrakis(p-carboxymethyleneoxyphenyl)porphyrin (SPTA) as a theranostic agent for applications in positron emission tomography (PET) and photodynamic therapy (PDT). SPTA was synthesized in-house following a three-step reaction process and characterized by using spectroscopic techniques, viz. UV-vis, FT-IR, ¹H-NMR and ¹³C-NMR spectroscopy, as well as by mass spectrometry. SPTA was labeled with ⁶⁸Ga, a generator produced PET radioisotope, and the radiolabeled product was characterized by HPLC. The ⁶⁸Ga-SPTA complex was prepared with a radiochemical purity of >95% under optimized conditions. The diagnostic potential of ⁶⁸Ga-SPTA was evaluated by cell uptake studies in two different tumor cell lines (HT1080 and A549) which revealed the affinity of ⁶⁸Ga-SPTA towards the cancer cells. Biodistribution studies carried out in Swiss mice bearing fibrosarcoma tumors exhibited the accumulation of the radiotracer in the tumor. The therapeutic potential of SPTA was evaluated by determining its photo-cytotoxicity employing the MTT assay in HT1080 and A549 cell lines using three different light doses, which indicated the significant cytotoxicity of SPTA in the presence of light. The present study indicates the possible potential of SPTA in radionuclide imaging as well as in photodynamic therapy (PDT) thus confirming the promising theranostic nature of this porphyrin derivative.