Modification of [18F]FMISO Radiosynthesis by Using a Non-Cassette-Based Synthesizer for Supporting Hypoxia Diagnosis in Cancer Patients in Thailand

Authors

  • Jiratthakorn Keeratipiriyakul Department of Applied Radiation and Isotopes, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
  • Wanwisa Sudprasert Department of Applied Radiation and Isotopes, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand

DOI:

https://doi.org/10.48048/tis.2022.5703

Keywords:

[18F]FMISO, Synthra RNplus, Radiosynthesis, Radiopharmaceuticals, Hypoxia

Abstract

In cancer cells, hypoxia can lead to resistance to both radiation and chemotherapy. The ability to measure cellular hypoxia is an useful tool in therapeutic planning. [18F]Fluoromisonidazole ([18F]FMISO) is a specific tracer used for the detection of hypoxic tissues by positron emission tomography (PET). In this research, the [18F]FMISO radiosynthesis has been modified to reduce costs to support clinical studies of patients with hypoxia by using an automated module instead of the disposable cassette-based synthesizer. The Synthra RNplus module, a remote-controlled synthesizer, was used for nucleophilic substitution of NITTP (1-(2'-nitro-1'-imidazolyl)-2-O-tetrahydropyranyl-3-O-toluenesulfonyl-propanediol) with [18F]fluoride anion. Labeling of the 5 mg of NITTP precursor in anhydrous dimethyl sulfoxide (DMSO) was performed at 100 ℃ for 10 min and hydrolyzed with 1 M hydrochloric acid (HCl) at 100 ℃ for 5 min. Finally, the purified product was obtained by using solid phase extraction (SPE) cartridge instead of high-performance liquid chromatography (HPLC). The total [18F]FMISO yield was approximately 29.11 ± 5.00 % (n = 7), the total synthesis time was less than 35 min, and the radiochemical purity was greater than 95 %. These results are very useful for supporting hypoxia diagnosis in cancer patients in Thailand.

HIGHLIGHTS

  • Rapid and simplified [18F]FMISO radiosynthesis are very useful for supporting hypoxia diagnosis in cancer patients in Thailand
  • [18F]FMISO radiosynthesis using Synthra RNplus with SPE purification takes less than 35 min
  • [18F]FMISO yield is approximately 29.11 ± 5.00 % (n = 7, non-decay corrected) and the radiochemical purity is greater than 95 %


GRAPHICAL ABSTRACT

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References

N Tangjaturonrasme, P Vatanasapt and A Bychkov. Epidemiology of head and neck cancer in Thailand. Asia Pac. J. Clin. Oncol. 2018; 14, 16-22.

L Tuntiyatorn, E Fusuwankaya, T Sawangsilpa and T Bhongmakapat. CT perfusion in predicting treatment response of nasopharyngeal carcinoma. J. Med. Assoc. Thai. 2014; 97, 333-41.

RG Bristow and RP Hill. Hypoxia and metabolism: Hypoxia, DNA repair and genetic instability. Nat. Rev. Canc. 2008; 8, 180-92

J Zhang, J Cao, S Ma, R Dong, W Meng, M Ying, Q Weng, Z Chen, J Ma, Q Fang, Q He and B Yang. Tumor hypoxia enhances non-small cell lung cancer metastasis by selectively promoting macrophage M2 polarization through the activation of ERK signaling. Oncotarget 2014; 5, 9664-77.

D Ackerman and MC Simon. Hypoxia, lipids, and cancer: Surviving the harsh tumor micro environment. Trends Cell Biol. 2014; 24, 472-8.

JM Brown. Tumor hypoxia in cancer therapy. Meth. Enzymol. 2007; 435, 297-321.

A Nagelkerke, J Bussink, H Mujcic, BG Wouters, S Lehmann, FC Sweep and PN Span. Hypoxia stimulates migration of breast cancer cells via the PERK/ATF4/LAMP3-arm of the unfolded protein response. Breast Canc. Res. 2013; 15, R2.

SGJA Peeters, CML Zegers, NG Lieuwes, W van Elmpt, J Eriksson, GAMS van Dongen, L Dubois and P Lambin. A comparative study of the hypoxia PET tracers [18F]HX4, [18F]FAZA, and [18F]FMISO in a preclinical tumor model. Int. J. Radiat. Oncol. Biol. Phys. 2015; 91, 351-9.

A Lin and SM Hahn. Hypoxia imaging markers and applications for radiation treatment planning. Semin. Nucl. Med. 2012; 42, 343-52.

CW Chang, TK Chou, RS Liu, SJ Wang, WJ Lin, CH Chen and HE Wang. A robotic synthesis of [18F]fluoromisonidazole ([18F]FMISO). Appl. Radiat. Isot. 2007; 65, 682-6.

M Wang, Y Zhang, Y Zhang and H Yuan. Automated synthesis of hypoxia imaging agent [18F]FMISO based upon a modified Explora FDG4 module. J. Radioanal. Nucl. Chem. 2009; 280, 149-55.

SJ Oh, DY Chi, C Mosdzianowski, JY Kim, HS Gil, SH Kang, JS Ryu and DH Moon. Fully automated synthesis of [18F]fluoromisonidazole using a conventional [18F]FDG module. Nucl. Med. Biol. 2005; 32, 899-905.

G Tang, M Wang, X Tang, M Gan and L Luo. Fully automated one-pot synthesis of [18F]fluoromisonidazole. Nucl. Med. Biol. 2005; 32, 553-8.

EL Kämäräinen, T Kyllönen, O Nihtilä, H Björk and O Solin. Preparation of fluorine‐18‐labelled fluoromisonidazole using two different synthesis methods. J. Labelled Comp. Rad. 2004; 47, 37-45.

S Nandy and M Rajan. Fully automated radiosynthesis of [18F] fluoromisonidazole with single neutral alumina column purification: Optimization of reaction parameters. J. Radioanal. Nucl. Chem. 2010; 286, 241-8.

E Blom and J Koziorowski. Automated synthesis of [18F]FMISO on IBA Synthera®. J. Radioanal. Nucl. Chem. 2014; 299, 265-70.

Synthra GmbH. Detailed specification of RNplus radiosynthesizer, Available at: http://www.synthra.com/download/specs/Synthra%20RNplus%20Specification.pdf, accessed February 2021.

K Kilian, B Chabecki, J Kiec, A Kunka, B Panas, M Wójcik and A Pękal. Synthesis, quality control and determination of metallic impurities in 18F-fludeoxyglucose production process. Rep. Practical Oncol. Radiother. 2014; 19, S22-S31.

Investigator’s Brochure for [18F]FMISO, updated specifications for IND 76,042. Cancer Imaging Program NCI, Available at: https://imaging.cancer.gov/programs_resources/cancer-tracer-synthesis-resources/docs/FMISO_spec_sheet.pdf, accessed February 2021.

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Published

2022-08-21

Issue

Vol. 19 No. 17 (2022): Trends in Sciences, Volume 19, Number 17, 1 September 2022

Section

Research Articles

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