Journal of Nuclear Science, Engineering and Technology (JONSAT)
In cooperation with the Iranian Nuclear Society

Radachlorin labeled Gallium-68 Pharmaceutical: a New Theranostic Agent for the Integration of Photodynamic Therapy and Nuclear Imaging

Document Type : Research Paper

Authors

S.Y. Fazaeli Hoseini Nezhad 1
F. Yari 2

1 Radiation Application Research School, Nuclear Science and Technology Research Institute, AEOI, P.O.Box: 11365-3486, Tehran-Iran

2 Radiation Application Research School, Nuclear Science and Technology Research Institute, AEOI, P.O.Box: 11365-3486, Tehran-IranDepartment of Nuclear Engineering, Science and Research Branch, Islamic Azad University, P.O.Box: 1477893855, Tehran-Iran

https://doi.org/10.24200/nst.2020.1115
Abstract
The cyclic tetrapyrrolic compounds, such as porphyrins, play an important role in medical research due to their fundamental role in the body of living beings, the ability to accumulate in various human cancer cells, as well as having distinct physical, magnetic, and optical properties. Therefore, they are very useful in the design of anticancer pharmaceuticals and photodynamic therapy agents. Due to the prominent properties of gallium -68 and the targeted accumulation of radachlorin anticancer drug, the radiopharmaceutical complex of this porphyrin is synthesized with gallium -68 radionuclide and its biological information such as partition coefficient and  biodistribution studies in normal and tumor-bearing rats were studied. The complex was prepared with acceptable radiochemical purity and stability in the final formulation and human serum for 4 h. The partition coefficient was -1.14. High accumulation of the complex in the tumor, rapid washout from the body, and lower absorbed radiation doses to patients were observed using this labeled compound. In this study combining the unique reactivity of gallium -68 with flat-lipophilic ligands with a neutral electric charge, such as radachlorin, the potential for beta-excretion for PET, and the use of radachlorin in PDT for therapeutic purposes, a new PET / PDT imaging agent was introduced.

Highlights

1.             J.F. Kelly, M.E. Snell, M.C. Berenbaum, Photodynamic Destruction of Human Bladder Carcinoma, Br. J. Cancer, 31, 237–244 (1975).

 

2.             J. Lu, et al, Mesoporous silica nanoparticles as a delivery system for hydrophobic anticancer drugs, Small, 3, 1341–1346 (2007).

 

3.             S. Nakajima, et al, Tumour enhancement with newly developed Mn-metalloporphyrin (HOP-9P) in magnetic resonance imaging of mice, Cancer Lett. 149, 221-226 (2000).

 

4.             B.W. Henderson, D.A. Bellnier, Tissue localization of photosensitizers and the mechanism of photodynamic tissue destruction, Ciba Found. Symp, 146, 112-125 (1989).

 

5.             Q. Peng, J. Moan, L.S. Cheng, Photostability of Drugs and drug Formulations, 3th ed, Cancer Lett. 58, 29-35 (1991).

 

6.             D. Kessel, The distribution of porphyrin with different tumor localizing ability among human Plasma Proteins, CaserLett, 33, 183-188 (1986).

 

7.             S. NaKajima, T. Takemura, I. Sakata, Tumor–localizing activity of porphyrin and its affinity to LDL, transferring, Cancer Lett, 92, 113-118 (1995).

 

8.             Y. Fazaeli, et al, Grafting of [(64)Cu]-TPPF20 porphyrin complex on Functionalized nano-porous MCM-41 silica as a potential cancer imaging agent, Appl Radiat Isot, 112, 13-9 (2016).

 

9.             A. Paknafas, et al, Radiosynthesis and Quality Control of [(67)Ga]-3,4-dimethoxylated Porphyrin Complex as a Possible Imaging agent, Iran J Pharm Res, 12(4), 735-44 (2013 Fall).

 

10.          Y. Fazaeli, et al, Development of a (68)Ga-Fluorinated Porphyrin Complex as a Possible PET Imaging Agent, Nucl Med Mol Imaging, 46(1), 20-26 (2012).

 

11.          Y. Fazaeli, et al, Preclinical dosimetric estimation of [111In] 5, 10, 15, 20-tetra phenyl porphyrin complex as a possible imaging/PDT agent, Radiochimica Acta, 104, 327-336 (2016).

 

12.          Y. Fazaeli, et al, Development of radiolabeled radachlorin complex as a possible tumor targeting agent, Journal of Radioanalytical and Nuclear Chemistry, 303, 1695-1701 (2015).

 

13.          Y. Fazaeli, A.R. Jalilian, A. Khalaj, Development of A New Radiogallium Porphyrin Complex as A Possible Tumor Imaging Agent, International Journal of Nuclear Medicine Research, 2, 7-15 (2015).

 

14.          S. Zolghadri, et al, Production, quality control, biodistribution assessment and preliminary dose evaluation of [177Lu]-tetra phenyl porphyrin complex as a possible therapeutic agent, Brazilian Journal of Pharmaceutical Sciences, 51, 339-345 (2015).

 

15.          N. Vahidfar, et al, Preparation of a 153Sm-5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin complex as a possible therapeutic agent, Iranian Journal of Nuclear Medicine, 23, 65-72 (2015).

 

16.          N. Vahidfar, A. Jalilian, Y. Fazaeli, Radiosynthesis and biological evaluation of 166Ho labeled methoxylated porphyrins as possible therapeutic agents, Journal of Radioanalytical and Nuclear Chemistry, 301, 269-276 (2014).

 

17.          N. Vahidfar, et al, Development and evaluation of a 166holmium labelled porphyrin complex as a possible therapeutic agent, Journal of Radioanalytical and Nuclear Chemistry, 295, 979-986 (2013).

Keywords

Radachlorin
Gallium -68
Porphyrin
Nuclear imaging
1.             J.F. Kelly, M.E. Snell, M.C. Berenbaum, Photodynamic Destruction of Human Bladder Carcinoma, Br. J. Cancer, 31, 237–244 (1975).
 
2.             J. Lu, et al, Mesoporous silica nanoparticles as a delivery system for hydrophobic anticancer drugs, Small, 3, 1341–1346 (2007).
 
3.             S. Nakajima, et al, Tumour enhancement with newly developed Mn-metalloporphyrin (HOP-9P) in magnetic resonance imaging of mice, Cancer Lett. 149, 221-226 (2000).
 
4.             B.W. Henderson, D.A. Bellnier, Tissue localization of photosensitizers and the mechanism of photodynamic tissue destruction, Ciba Found. Symp, 146, 112-125 (1989).
 
5.             Q. Peng, J. Moan, L.S. Cheng, Photostability of Drugs and drug Formulations, 3th ed, Cancer Lett. 58, 29-35 (1991).
 
6.             D. Kessel, The distribution of porphyrin with different tumor localizing ability among human Plasma Proteins, CaserLett, 33, 183-188 (1986).
 
7.             S. NaKajima, T. Takemura, I. Sakata, Tumor–localizing activity of porphyrin and its affinity to LDL, transferring, Cancer Lett, 92, 113-118 (1995).
 
8.             Y. Fazaeli, et al, Grafting of [(64)Cu]-TPPF20 porphyrin complex on Functionalized nano-porous MCM-41 silica as a potential cancer imaging agent, Appl Radiat Isot, 112, 13-9 (2016).
 
9.             A. Paknafas, et al, Radiosynthesis and Quality Control of [(67)Ga]-3,4-dimethoxylated Porphyrin Complex as a Possible Imaging agent, Iran J Pharm Res, 12(4), 735-44 (2013 Fall).
 
10.          Y. Fazaeli, et al, Development of a (68)Ga-Fluorinated Porphyrin Complex as a Possible PET Imaging Agent, Nucl Med Mol Imaging, 46(1), 20-26 (2012).
 
11.          Y. Fazaeli, et al, Preclinical dosimetric estimation of [111In] 5, 10, 15, 20-tetra phenyl porphyrin complex as a possible imaging/PDT agent, Radiochimica Acta, 104, 327-336 (2016).
 
12.          Y. Fazaeli, et al, Development of radiolabeled radachlorin complex as a possible tumor targeting agent, Journal of Radioanalytical and Nuclear Chemistry, 303, 1695-1701 (2015).
 
13.          Y. Fazaeli, A.R. Jalilian, A. Khalaj, Development of A New Radiogallium Porphyrin Complex as A Possible Tumor Imaging Agent, International Journal of Nuclear Medicine Research, 2, 7-15 (2015).
 
14.          S. Zolghadri, et al, Production, quality control, biodistribution assessment and preliminary dose evaluation of [177Lu]-tetra phenyl porphyrin complex as a possible therapeutic agent, Brazilian Journal of Pharmaceutical Sciences, 51, 339-345 (2015).
 
15.          N. Vahidfar, et al, Preparation of a 153Sm-5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin complex as a possible therapeutic agent, Iranian Journal of Nuclear Medicine, 23, 65-72 (2015).
 
16.          N. Vahidfar, A. Jalilian, Y. Fazaeli, Radiosynthesis and biological evaluation of 166Ho labeled methoxylated porphyrins as possible therapeutic agents, Journal of Radioanalytical and Nuclear Chemistry, 301, 269-276 (2014).
 
17.          N. Vahidfar, et al, Development and evaluation of a 166holmium labelled porphyrin complex as a possible therapeutic agent, Journal of Radioanalytical and Nuclear Chemistry, 295, 979-986 (2013).

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