Easily automated radiosynthesis of [18F]P10A-1910 and its clinical translation to quantify phosphodiesterase 10A in human brain

Huiyi Wei; Junjie Wei; Shaojuan Zhang; Shiliang Dong; Guocong Li; Wenqing Ran; Chenchen Dong; Weibin Zhang; Chao Che; Wenzhao Luo; Hao Xu; Zhiyong Dong; Jinghao Wang; Lu Wang

doi:10.3389/fbioe.2022.983488

Easily automated radiosynthesis of [¹⁸F]P10A-1910 and its clinical translation to quantify phosphodiesterase 10A in human brain

Front Bioeng Biotechnol. 2022 Sep 6:10:983488. doi: 10.3389/fbioe.2022.983488. eCollection 2022.

Authors

Huiyi Wei¹, Junjie Wei¹, Shaojuan Zhang¹, Shiliang Dong², Guocong Li¹, Wenqing Ran¹, Chenchen Dong¹, Weibin Zhang³, Chao Che³, Wenzhao Luo⁴, Hao Xu¹, Zhiyong Dong^{2

5}, Jinghao Wang^{5

6}, Lu Wang^{1

5}

Affiliations

¹ Center of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, China.
² Center of Bariatric Surgery, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
³ State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China.
⁴ Institute of Analysis, Guangdong Academy of Sciences (China National Analytical Center), Guangzhou, China.
⁵ The Guangzhou Key Laboratory of Basic and Translational Research on Chronic Diseases, The First Affiliated Hospital of Jinan University, Guangzhou, China.
⁶ Department of Pharmacy, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Abstract

Our previous work showed that [¹⁸F]P10A-1910 was a potential radioligand for use in imaging phosphodiesterase 10A (PDE10A). Specifically, it had high brain penetration and specific binding that was demonstrated in both rodents and non-human primates. Here, we present the first automatic cGMP-level production of [¹⁸F]P10A-1910 and translational PET/MRI study in living human brains. Successful one-step radiolabeling of [¹⁸F]P10A-1910 on a GE TRACERlab FX2N synthesis module was realized via two different methods. First, formulated [¹⁸F]P10A-1910 was derived from heating spirocyclic iodonium ylide in a tetra-n-butyl ammonium methanesulfonate solution. At the end of synthesis, it was obtained in non-decay corrected radiochemical yields (n.d.c. RCYs) of 12.4 ± 1.3%, with molar activities (MAs) of 90.3 ± 12.6 μmol (n = 7) (Method I). The boronic pinacol ester combined with copper and oxygen also delivered the radioligand with 16.8 ± 1.0% n. d.c. RCYs and 77.3 ± 20.7 GBq/μmol (n = 7) MAs after formulation (Method II). The radiochemical purity, radionuclidic purity, solvent residue, sterility, endotoxin content and other parameters were all validated for human use. Consistent with the distribution of PDE10A in the brain, escalating uptake of [¹⁸F]P10A-1910 was observed in the order of cerebellum (reference region), substantial nigra, caudate and putamen. The non-displaceable binding potential (BP _ND) was estimated by simplified reference-tissue model (SRTM); linear regressions demonstrated that BP _ND was well correlated with the most widely used semiquantitative parameter SUV. The strongest correlation was observed with SUV_{(50-60 min)} (R ² = 0.966, p < 0.01). Collectively, these results indicated that a static scan protocol could be easily performed for PET imaging of PDE10A. Most importantly, that [¹⁸F]P10A-1910 is a promising radioligand to clinically quantify PDE10A.

Keywords: automatic radiosynthesis; human brain; phosphodiesterase 10A; positron emission tomography; translational PET/MRI.