Synthesis and evaluation of radiolabeled porphyrin derivatives for cancer diagnoses and their nonradioactive counterparts for photodynamic therapy

Nur Izni Ramzi; Kenji Mishiro; Masayuki Munekane; Takeshi Fuchigami; Xiaojun Hu; Renata Jastrząb; Yoji Kitamura; Seigo Kinuya; Kazuma Ogawa

doi:10.1039/d2md00234e

Synthesis and evaluation of radiolabeled porphyrin derivatives for cancer diagnoses and their nonradioactive counterparts for photodynamic therapy

RSC Med Chem. 2022 Sep 22;13(12):1565-1574. doi: 10.1039/d2md00234e. eCollection 2022 Dec 14.

Authors

Nur Izni Ramzi¹, Kenji Mishiro², Masayuki Munekane¹, Takeshi Fuchigami¹, Xiaojun Hu³, Renata Jastrząb⁴, Yoji Kitamura⁵, Seigo Kinuya⁶, Kazuma Ogawa^{1

2}

Affiliations

¹ Graduate School of Pharmaceutical Sciences, Kanazawa University Kakuma-machi Kanazawa Ishikawa 920-1192 Japan kogawa@p.kanazawa-u.ac.jp.
² Institute for Frontier Science Initiative, Kanazawa University Kakuma-machi Kanazawa Ishikawa 920-1192 Japan.
³ Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University Shanghai 200444 China.
⁴ Faculty of Chemistry, Adam Mickiewicz University of Poznan Uniwersytetu Poznanskiego 8 Poznan 61-614 Poland.
⁵ Research Center for Experimental Modeling of Human Disease, Kanazawa University Takara-machi 13-1 Kanazawa Ishikawa 920-8640 Japan.
⁶ Department of Nuclear Medicine, Kanazawa University Hospital, Kanazawa University Takara-machi 13-1 Kanazawa Ishikawa 920-8641 Japan.

Abstract

Radioiodinated porphyrin derivatives and the corresponding nonradioactive iodine introduced compounds, [¹²⁵I]I-TPP_OH ([¹²⁵I]3), [¹²⁵I]I-l-tyrosine-TPP ([¹²⁵I]9), I-TPP_OH (3), and I-l-tyrosine-TPP (9) were designed, synthesized, and evaluated by in vitro and in vivo experiments. In cytotoxicity assays, 3 and 9 exhibited significant cytotoxicity under light conditions but did not show significant cytotoxicity without light irradiation. Biodistribution experiments with [¹²⁵I]3 and [¹²⁵I]9 showed similar distribution patterns with high retention in tumors. In photodynamic therapeutic (PDT) experiments, 3 and 9 at a dose of 13.6 μmol kg^-1 weight with 50 W single light irradiation onto the tumor area significantly inhibited tumor growth. These results indicate that the iodinated porphyrin derivatives [^123/natI]3 and [^123/natI]9 are promising cancer theranostic agents.