Asia Oceania Journal of Nuclear Medicine and Biology

Asia Oceania Journal of Nuclear Medicine and Biology

On the Optimization of the Protocol for Automated Radiosyntheses of [68Ga]Ga-Pentixafor, [68Ga]Ga-FAPI-4 and [68Ga]Ga-DOTATATE in a Modular-Lab Standard

Document Type : Original Article

Authors
Sreeja Raj Menon 1, 2
Arpit Mitra 3
Sudeep Sahu 4
Sangita Lad 4
Avik Chakraborty 2, 4
Mukti Kanta Ray 2, 4
Sharmila Banerjee 2, 5
1 Health Physics Division, Bhabha Atomic Research Centre, Mumbai, India
2 Homi Bhabha National Institute, Mumbai, India
3 Radiopharmaceutical Laboratory, Board of Radiation and Isotope Technology, Navi Mumbai, India
4 Radiation Medicine Centre, Bhabha Atomic Research Centre, Mumbai, India
5 Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India
10.22038/aojnmb.2024.77059.1545
Abstract
Objective: The present work describes the automated radiochemical syntheses of different PET tracers like [68Ga]Ga-Pentixafor, [68Ga]Ga-FAPI-4 and [68Ga]Ga-DOTATATE using optimized single protocol in the non-cassette based Eckert & Ziegler (EZ) Modular Lab (fixed tubing system) without any modification in the inbuilt human machine interface (HMI) software. Recently, PET agents viz. [68Ga]Ga-Pentixafor and [68Ga]Ga-FAPI-4 are gaining prominence for the diagnosis of overexpressed Chemokine Receptor-4 (CXCR4) and Fibroblast Activation Protein (FAP) receptor, respectively, in the microenvironment of numerous cancer types. The promising results observed with the clinical usage of [68Ga]Ga-DOTATATE produced using the automated protocol, provided impetus for the clinical translation of [68Ga]Ga-Pentixafor and [68Ga]Ga-FAPI-4 using the in-house developed automated radiolabeling protocol.
Methods: Herein we report a single radiolabeling protocol for the automated preparation of [68Ga]Ga-Pentixafor and [68Ga]Ga-FAPI-4 in the non-cassette based EZ Modular-Lab Standard radiochemistry module, without any changes in schematic, graphical user interface (GUI) software and time list, from that used for routine production of [68Ga]Ga-DOTATATE in our centre, since 2015. Physico-chemical quality control and in-vitro stability analyses were carried out using radio-TLC and radio-HPLC.
Results: The automated protocol yielded reliable and consistent non-decay corrected (ndc) radiochemical yield (RCY) of (84.4±0.9)% and (85.5±1.4)% respectively, for [68Ga]Ga-Pentixafor and [68Ga]Ga-FAPI-4, with RCP> 98%, which are comparable to the RCY of (84.4±1.2)% and RCP (99.1±0.3)% for [68Ga]Ga-DOTATATE. The biological quality control studies confirmed the formulations to be of ready-to-use pharmaceutical grade.
Conclusion: The consistent and reliable RCY and RCP of multiple 68Ga-labeled PET tracers by single optimized automated radiochemistry protocol exhibits the versatility of the EZ Modular Lab.
Keywords
[68Ga]Ga-Pentixafor
[68Ga]Ga-FAPI-4
[68Ga]Ga-DOTATATE
Modular-Lab Standard
PET/CT
Subjects
  1. Banerjee SR, Pomper MG. Clinical applications of Gallium-68. Applied Radiation and Isotopes. 2013; 76: 2-13.
  2. Le Pennec R, Iravani A, Woon B, Dissaux B, Gest B, Le Floch PY, Salaün PY, Le Gal G, Hofman MS, Hicks RJ, Le Roux PY. Gallium-68 Ventilation/Perfusion PET-CT and CT Pulmonary Angiography for Pulmonary Embolism Diagnosis: An Interobserver Agreement Study. Frontiers in Medicine. 2021; 7:599901.
  3. Wichmann CW, Ackermann U, Poniger S, Young K, Nguyen B, Chan G, Sachinidis J, Scott AM. Automated radiosynthesis of [68Ga] Ga‐PSMA‐11 and [177Lu] Lu‐PSMA‐617 on the iPHASE MultiSyn module for clinical applications. Journal of Labelled Compounds and Radiopharmaceuticals. 2021; 64(3):140-6.
  4. Boschi S, Lodi F, Malizia C, Cicoria G, Marengo M. Automation synthesis modules review. Applied radiation and isotopes. 2013; 76:38-45.
  5. Sanchez-Crespo A. Comparison of Gallium-68 and Fluorine-18 imaging characteristics in positron emission tomography. Applied Radiation and Isotopes. 2013; 76: 55-62.
  6. Garcia‐Arguello SF, Lopez‐Lorenzo B, Ruiz‐Cruces R. Automated production of [68Ga] Ga‐DOTANOC and [68Ga] Ga‐PSMA‐11 using a TRACERlab FXFN synthesis module. Journal of Labelled Compounds and 2019; 62(3): 146-53.
  7. Boschi S, Malizia C, Lodi F. Overview and perspectives on automation strategies in (68)Ga radiopharmaceutical preparations. Recent Results Cancer Res. 2013; 194:17-31.
  8. Scala S, Giuliano P, Ascierto PA, Ieranò C, Franco R, Napolitano M, Ottaiano A, Lombardi ML, Luongo M, Simeone E, Castiglia D. Human melanoma metastases express functional CXCR4. Clinical cancer research. 2006: 12(8):2427-33.
  9. Scala S, Ottaiano A, Ascierto PA, Cavalli M, Simeone E, Giuliano P, Napolitano M, Franco R, Botti G, Castello G. Expression of CXCR4 predicts poor prognosis in patients with malignant melanoma. Clinical Cancer Research. 2005; 11(5):1835-41.
  10. Mei L, Liu Y, Zhang Q, Gao H, Zhang Z, He Q. Enhanced antitumor and anti-metastasis efficiency via combined treatment with CXCR4 antagonist and liposomal doxorubicin. Journal of Controlled Release. 2014; 196: 324-31.
  11. André ND, Silva VA, Ariza CB, Watanabe MA, De Lucca FL. In vivo knockdown of CXCR4 using jetPEI/CXCR4 shRNA nanoparticles inhibits the pulmonary metastatic potential of B16‑F10 melanoma cells. Mol Med Rep. 2015; 12(6):8320-6.
  12. André ND, Silva VA, Watanabe MA, De Lucca FL. Knockdown of chemokine receptor CXCR4 gene by RNA interference: Effects on the B16-F10 melanoma growth. Oncol Rep. 2016; 35(4):2419-24.
  13. Spreckelmeyer S, Schulze O, Brenner W. Fully-automated production of [68Ga] Ga-PentixaFor on the module Modular Lab-PharmTracer. EJNMMI Radiopharm Chem. 2020; 5(1):8.
  14. Da Pieve C, Costa Braga M, Turton DR, Valla FA, Cakmak P, Plate KH, Kramer-Marek G. New Fully Automated Preparation of High Apparent Molar Activity 68Ga-FAPI-46 on a Trasis AiO Platform. Molecules. 2022; 27(3):675.
  15. Alfteimi A, Lützen U, Helm A, Jüptner M, Marx M, Zhao Y, Zuhayra M. Automated synthesis of [68Ga]Ga-FAPI-46 without pre-purification of the generator eluate on three common synthesis modules and two generator types. EJNMMI Radiopharm Chem. 2022; 7(1):20.
  16. Spreckelmeyer S, Balzer M, Poetzsch S, Brenner W. Fully-automated production of [68Ga]Ga-FAPI-46 for clinical application. EJNMMI Radiopharm Chem. 2020; 5(1):31.
  17. Waters Oasis. Simplifying solid phase extraction. 2007. [Accessed 6 Nov 2023]. Available from: https:// www.waters.com/ webassets/cms/library/docs/720001692en.pdf.
  18. Zwir-Ference A, Biziuk M. Solid Phase Extraction Technique – Trends, Opportunities and Applications. Polish J of Environ Stud. 2006; 15(5):677-690.
  19. Mitra A, Chakraborty A, Upadhye T, Tawate M, Lad S, Sahu S, Rajesh C, Bagul S, Pawar Y, Ray MK, Banerjee S. Automated radiochemical synthesis of pharmaceutical grade [18F] FLT using 3‐N‐Boc‐5′‐O‐dimethoxytrityl‐3′‐O‐nosyl‐thymidine precursor and its Sep‐Pak® purification employing selective elution from reversed phase. Journal of Labelled Compounds and Radio-table 1pharmaceuticals. 2022 65(8): 206-22.
Asia Oceania Journal of Nuclear Medicine and Biology
Volume 12, Issue 2
July 2024
Pages 149-160