Automated PET Radiotracer Manufacture on the BG75 System and Imaging Validation Studies of [18F]fluoromisonidazole ([18F]FMISO)

Title:Automated PET Radiotracer Manufacture on the BG75 System and Imaging Validation Studies of [18F]fluoromisonidazole ([18F]FMISO)

Volume: 9 Issue: 3

Author(s): Hong Yuan, Jonathan E. Frank, Joseph R. Merrill, Daniel A. Hillesheim, Mark H. Khachaturian and Atilio I. Anzellotti

Affiliation:

Keywords: [¹⁸F]FMISO, hypoxia, PET, solid-phase extraction, system BG75, tumor hypoxia.

Abstract: Background and Objective: The hypoxia PET tracer, 1-[¹⁸F]fluoro-3-(2-nitro-1Himidazol- 1-yl)-propan-2-ol ([¹⁸F]FMISO) is the first radiotracer developed for hypoxia PET imaging and has shown promising for cancer diagnosis and prognosis. However, access to [¹⁸F]FMISO radiotracer is limited due to the needed cyclotron and radiochemistry expertise. The study aimed to develop the automated production method on the [¹⁸F]FMISO radiotracer with the novel fully automated platform of the BG75 system and validate its usage on animal tumor models.

Method: [¹⁸F]FMISO was produced with the dose synthesis cartridge automatically on the BG75 system. Validation of [¹⁸F]FMISO hypoxia imaging functionality was conducted on two tumor mouse models (FaDu/U87 tumor). The distribution of [¹⁸F]FMISO within tumor was further validated by the standard hypoxia marker EF5.

Results: The average radiochemical purity was (99±1) % and the average pH was 5.5±0.2 with other quality attributes passing standard criteria (n=12). Overall biodistribution for [¹⁸F]FMISO in both tumor models was consistent with reported studies where bladder and large intestines presented highest activity at 90 min post injection. High spatial correlation was found between [¹⁸F]FMISO autoradiography and EF5 hypoxia staining, indicating high hypoxia specificity of [¹⁸MF]FMISO.

Conclusion: This study shows that qualified [¹⁸F]FMISO can be efficiently produced on the BG75 system in an automated “dose-on-demand” mode using single dose disposable cards. The possibilities of having a low-cost, automated system manufacturing ([¹⁸F]Fluoride production + synthesis + QC) different radiotracers will greatly enhance the potential for PET technology to reach new geographical areas and underserved patient populations.

Cite this article as:

Yuan Hong, Frank E. Jonathan, Merrill R. Joseph, Hillesheim A. Daniel, Khachaturian H. Mark and Anzellotti I. Atilio, Automated PET Radiotracer Manufacture on the BG75 System and Imaging Validation Studies of [18F]fluoromisonidazole ([18F]FMISO), Current Radiopharmaceuticals 2016; 9 (3) . https://dx.doi.org/10.2174/1874471009666160725100940