In vivo multimodal tumor imaging and photodynamic therapy with novel theranostic agents based on the porphyrazine framework-chelated gadolinium (III) cation

• Published in: Biochimica et biophysica acta. General subjects 2017-12, Vol.1861 (12), p.3120-3130
• Main Authors: Yuzhakova, Diana V., Lermontova, Svetlana A., Grigoryev, Ilya S., Muravieva, Maria S., Gavrina, Alena I., Shirmanova, Marina V., Balalaeva, Irina V., Klapshina, Larisa G., Zagaynova, Elena V.
• Format: Article
• Language: English
• Subjects: Animals; Bimodal contrast agent; Cell Line, Tumor; Chelating Agents - administration & dosage; Fluorescence; Fluorescence imaging; Gadolinium; Magnetic Resonance Imaging; Mice; Mice, Inbred BALB C; MRI; Multifunctional agent; Multimodal Imaging; Neoplasms - diagnostic imaging; Neoplasms - drug therapy; PDT; Photochemotherapy; Tumor model
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2017.09.004

A promising strategy for cancer diagnosis and therapy is the development of an agent for multimodal imaging and treatment. In the present paper we report on two novel multifunctional agents prepared on the porphyrazine pigment platform using a gadolinium (III) cation chelated by red-fluorescent tetrapyrrole macrocycles (GdPz1 and GdPz2). Spectral and magnetic properties of the compounds were analyzed. Monitoring of GdPz1 and GdPz2 accumulation in the murine colon carcinoma CT26 was performed in vivo using fluorescence imaging and MRI. The photobleaching of GdPz1 or GdPz2 and tumor growth rate after photodynamic therapy (PDT) were assessed. GdPz1 and GdPz2 demonstrated the selective accumulation in tumor that was indicated by higher fluorescence intensity in the tumor area in comparison with the normal tissues. The results of MRI in vivo showed that GdPz1 or GdPz2 provided significant contrast enhancement of the tumor in T1 MR images. PDT with GdPz2 resulted in ~20% decrease in fluorescence intensity of the compound and the inhibition of tumor growth. We assessed the efficiency of two innovative Gd(III) cation-porphyrazine chelates as bimodal MR and fluorescent probes and photosensitizers for PDT and showed their potentials for tumor diagnostics and treatment. Water-soluble structures simple in preparation and administration into the body represent special interest for theranostics of tumors. Novel porphyrazine macrocycles chelating a central gadolinium cation demonstrated a good prospect as effective multimodal agents, representing a new approach to MRI and fluorescence imaging guided PDT. •Two novel Gd(III) cation-porphyrazine chelates have been prepared.•The novel agents may serve as effective multimodal agents for cancer diagnostics.•The possibility of photodynamic therapy of cancer with novel agent was shown.