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Development and application of a fully automatic multi-function cassette module Mortenon M1 for radiopharmaceutical synthesis

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Abstract

Introduction

Functions of existing automatic module systems for synthesis of radiopharmaceuticals mainly focus on the radiolabeling of small molecules. There are few modules which have achieved full-automatic radiolabeling of non-metallic and metallic nuclides on small molecules, peptides, and antibody drugs. This study aimed to develop and test a full-automatic multifunctional module system for the safe, stable, and efficient production of radiopharmaceuticals.

Methods

According to characteristics of labeling process of radioactive drugs, using UG and Solidworks softwares, full-automatic cassette-based synthesis module system Mortenon M1 for synthesis of radiopharmaceuticals with various radionuclides, was designed and tested. Mortenon M1 has at least three significant highlights: the cassettes are disposable, and there is no need of manual cleaning; the synthesis method program is flexible and can be edited freely by users according to special needs; this module system is suitable for radiolabeling of both small-molecule and macromolecular drugs, with potentially various radionuclides including 18F, 64Cu, 68Ga, 89Zr, 177Lu, etc. By program control methods for certain drugs, Mortenon M1 was used for radiolabeling of both small-molecule drugs such as [68Ga]-FAPI-46 and macromolecular drugs such as [89Zr]-TROP2 antibody. Quality control assays for product purity were performed with radio-iTLC and radio-HPLC, and the radiotracers were confirmed for application in microPET imaging in xenograft tumor-bearing mouse models.

Results

Functional tests for Mortenon M1 module system were conducted, with [68Ga]-FAPI-46 and [89Zr]-TROP2 antibody as goal synthetic products, and it displayed that with the cassette modules, the preset goals could be achieved successfully. The radiolabeling synthesis yield was good ([68Ga]-FAPI-46, 70.63% ± 2.85%, n = 10; [89Zr]-TROP2, 82.31% ± 3.92%, n = 10), and the radiochemical purity via radio-iTLC assay of the radiolabeled products was above 99% after purification. MicroPET imaging results showed that the radiolabeled tracers had reasonable radioactive distribution in MDA-MB-231 and SNU-620 xenograft tumor-bearing mice, and the tumor targeted radiouptake was satisfactory for diagnosis.

Conclusion

This study demonstrated that the full-automatic module system Mortenon M1 is efficient for radiolabeling synthesis of both small-molecule and macromolecular substrates. It may be helpful to reduce radiation exposure for safety, provide qualified radiolabeled products and reliable PET diagnosis, and ensure stable production and supply of radiopharmaceuticals.

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Availability of data and materials

Data are contained within the article, and the datasets used and/or analyzed during the current study are available from the corresponding authors on reasonable request.

Abbreviations

%ID/g:

Percentage of injected radioactivity dose per gram

FAPI:

Fibroblast activation protein inhibitor

GMP:

Good manufacturing practice of medical products

HEPES:

2-[4-(2-Hydroxyethyl)-1-piperazinyl]ethanesulfonic acid

iTLC:

Instant thin-layer chromatography

OD:

Outside diameter

PET:

Positron emission tomography

PLC:

Programmable logic controller

Radio-HPLC:

Radioactive high-performance liquid chromatography

ROIs:

Regions of interest

RT:

Retention time

TROP2:

Trophoblast cell-surface antigen-2

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Acknowledgements

The authors are grateful to Norroy Bioscience for financial, technical, and material supports.

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Authors and Affiliations

  1. Department of Oncology, The People’s Hospital of Ma Anshan, Ma Anshan, 243000, Anhui, People’s Republic of China

    Fang-Bo Cui

  2. Norroy Bioscience Co., Ltd, Building 2, Lihu Business Park, Zhongbang MOHO, Huize Road, Binhu District, Wuxi, 214000, Jiangsu, People’s Republic of China

    Xuan Lv, Cheng-Long Yan, Wai-Si Eng & Shan-You Yu

  3. Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 112, Indianapolis, IN, 46202, USA

    Qi-Huang Zheng

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Contributions

F-BC and S-YY: conceived and designed the modular system, performed most of the tests and experiments, and drafted the manuscript. XL and C-LY helped in tests and experiments, and analyzed data. W-SE gave useful suggestion and discussed the manuscript. Q-HZ: supported in methodology, supervised the project, and revised the manuscript.

Corresponding authors

Correspondence to Shan-You Yu or Qi-Huang Zheng.

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Conflict of interest

All the authors declare that they have no conflict of interest relevant to this article.

Ethical approval

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Animal Care and Use Committee of the People’s Hospital of Ma Anshan (Batch No.: ME2021-008-012, date of approval: Aug 28, 2021), and all animal experiments were conducted in compliance with the Guide for the Care and Use of Medical Laboratory Animals (Ministry of Health, China) and institutional guidelines. All the animals were maintained under anesthesia during the model-building, tracer injection, and scanning periods to avoid animal suffering.

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Cui, FB., Lv, X., Yan, CL. et al. Development and application of a fully automatic multi-function cassette module Mortenon M1 for radiopharmaceutical synthesis. Ann Nucl Med 38, 247–263 (2024). https://doi.org/10.1007/s12149-023-01893-2

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