2024, Volume 26, Issue 2
Strategic Study of CAE >> 2024, Volume 26, Issue 2 doi: 10.15302/J-SSCAE-2024.02.009
Innovative Development of Reactor-Produced Radionuclides and Radiopharmaceuticals
1. Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang 621900, Sichuan, China;
2. School of Medicine, Tsinghua University, Beijing 100084, China;
3. Chinese Academy of Engineering Innovation Strategy, Beijing 100088, China;
4. Chinese Academy of Engineering Physics, Beijing 100088, China
Next Previous
Abstract
Radionuclides and radiopharmaceuticals produced by reactors are important components and main material foundations of the nuclear healthcare industry. Therefore, summarizing the current status of reactor-produced radionuclides and radiopharmaceuticals is practically significant for accelerating the development of these products in China and promoting the construction of a self-reliant full-chain system. Through literature review, questionnaire survey, field research, and industry discussions, this study analyzes the supply and demand situation, current status, and trends of reactor-produced radionuclides and radiopharmaceuticals in China and abroad. Currently, China has achieved independent supply of a small number of reactor-produced radionuclides such as 131I, 177Lu, and 89Sr; however, the production capacity of these radionuclides cannot meet domestic demand, and most commonly used radionuclides in clinical practice still rely on imports. Meanwhile, the current reactor-produced radiopharmaceuticals face bottlenecks such as a limited variety of drugs, insufficient research and development innovation, and limited production capacity, making it difficult to meet actual clinical needs. Therefore, the supply and diversification of reactor-produced radionuclides should be ensured considering the current status and trends of their supply and demand. It is necessary to promote the large-scale preparation of reactorproduced radionuclides based on clinical needs, support the development and application of more innovative radiopharmaceuticals, and further accelerate the formation of a self-reliant development system for the reactor-produced radionuclides and radiopharmaceuticals in China. Additionally, it is urgent to enrich development models and form innovative concepts, providing reliable support for the sustainable development of nuclear medicine in China.
Keywords
reactor ; medical radionuclides ; radiopharmaceuticals ; supply and demand situation ; independence
References
[ 1 ]
彭述明, 杨宇川, 杨夏, 等. 我国放射性药物创新体系发展战略研究 [J]. 中国工程科学, 2022, 24(6): 116‒126.
Peng S M, Yang Y C, Yang X, et al. Development strategy for innovation system of radiopharmaceuticals in China [J]. Strategic Study of CAE, 2022, 24(6): 116‒126.
[ 2 ]
彭述明, 杨宇川, 谢翔, 等. 我国堆照医用同位素生产及应用现状与展望 [J]. 科学通报, 2020, 65(32): 3526‒3537.
Peng S M, Yang Y C, Xie X, et al. Current status and prospects of reactor produced medical radioisotopes in China [J]. Chinese Science Bulletin, 2020, 65(32): 3526‒3537.
[ 3 ] Akbar M U, Ahmad M R, Shaheen A, et al. A review on evaluation of technetium-99 m labeled radiopharmaceuticals [J]. Journal of Radioanalytical and Nuclear Chemistry, 2016, 310(2): 477‒493.
[ 4 ] Eryilmaz K, Kilbas B. Fully-automated synthesis of 177Lu labelled FAPI derivatives on the module modular lab-Eazy [J]. EJNMMI Radiopharmacy and Chemistry, 2021, 6(1): 16.
[ 5 ] Hofman M S, Violet J, Hicks R J, et al. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): A single-centre, single-arm, phase 2 study [J]. The Lancet Oncology, 2018, 19(6): 825‒833.
[ 6 ] Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 trial of 177Lu-dotatate for midgut neuroendocrine tumors [J]. The New England Journal of Medicine, 2017, 376(2): 125‒135.
[ 7 ] Stewart M W A, Vance E R, Moricca S A, et al. Immobilisation of higher activity wastes from nuclear reactor production of 99Mo [J]. Science and Technology of Nuclear Installations, 2013, 2013: 926026.
[ 8 ] Mang´era K, Ogbomo K, Zriba R, et al. Processing and evaluation of linear accelerator-produced 99Mo/99mTc in Canada [J]. Journal of Radioanalytical and Nuclear Chemistry, 2015, 305(1): 79‒85.
[ 9 ] Qiu L, Wang Y W, Liu H X, et al. Safety and efficacy of 68Ga- or 177Lu-labeled DOTA-IBA as a novel theranostic radiopharmaceutical for bone metastases: A phase 0/I study [J]. Clinical Nuclear Medicine, 2023, 48(6): 489‒496.
[10] Bodei L S, Herrmann K, Schöder H, et al. Radiotheranostics in oncology: Current challenges and emerging opportunities [J]. Nature Reviews Clinical Oncology, 2022, 19(8): 534‒550.
[11] FDA-approved drugs [EB/OL]. (2023-12-30)[2024-01-20]. https://www.accessdata.fda.gov/scripts/cder/daf/.
[12] Sever O N, Elboga U, Sahin E, et al. 177Lu-PSMA-617 RLT in mCRPC: A single center experience, the earlier could be the better [J]. Revista Espanola De Medicina Nuclear e Imagen Molecular, 2023, 42(2): 71‒76.
[13] Zang J, Fan X R, Wang H, et al. First-in-human study of 177Lu-EB-PSMA-617 in patients with metastatic castration-resistant prostate cancer [J]. European Journal of Nuclear Medicine and Molecular Imaging, 2019, 46(1): 148‒158.
[14]
施婧琦, 武新宇, 李博, 等. 定量 99Tcm-HYNIC-PSMA SPECT/CT诊断前列腺癌的价值 [J]. 中华核医学与分子影像杂志, 2022, 42(3): 149‒153.
Shi J Q, Wu X Y, Li B, et al. Clinical value of quantitative 99Tcm-HYNIC-PSMA SPECT/CT in the diagnosis of prostate cancer [J]. Chinese Journal of Nuclear Medicine and Molecular Imaging, 2022, 42(3): 149‒153.
[15] Dash A, Pillai M R A, Jr Knapp F F. Production of (177)Lu for targeted radionuclide therapy: Available options [J]. Nuclear Medicine and Molecular Imaging, 2015, 49(2): 85‒107.
[16]
卓连刚, 杨宇川, 岳海东, 等. DGA树脂辅助的循环淋洗技术制备无载体镥[177Lu] [J]. 同位素, 2022, 35(3): 217‒223.
Zhuo L G, Yang Y C, Yue H D, et al. Preparation of No-carrier-added 177Lu by DGA resin assisted cyclic elution [J]. Journal of Isotopes, 2022, 35(3): 217‒223.
[17] Golabi-Dezfoli A, Yousefnia H, Hosntalab M, et al. Optimized production, quality control and biodistribution assessment of 166Ho-DOTATOC: A novel radiolabelled somatostatin analog [J]. Journal of Radioanalytical and Nuclear Chemistry, 2017, 312(2): 329‒335.
[18] Pareek P, Singh S K, B Mehta D, et al. Application of hollow fibre membrane contactor for ultra purification of 90Sr nitrate solution at bulk scale for 90Sr‒90Y generator for societal use [J]. Journal of Radioanalytical and Nuclear Chemistry, 2022, 331(11): 4625‒4634.
[19] Baum R P, Singh A, Kulkarni H R, et al. First-in-humans application of 161Tb: A feasibility study using 161Tb-DOTATOC [J]. Journal of Nuclear Medicine, 2021, 62(10): 1391‒1397.
[20] Alcocer-Ávila M E, Ferreira A, Quinto M A, et al. Radiation doses from 161Tb and 177Lu in single tumour cells and micrometastases [J]. EJNMMI Physics, 2020, 7(1): 33.
[21] Su F M, Beaumier P, Axworthy D, et al. Pretargeted radioimmunotherapy in tumored mice using an in vivo 212Pb/212Bi generator [J]. Nuclear Medicine and Biology, 2005, 32(7): 741‒747.
[22] Li R G, Stenberg V Y, Larsen R H. An experimental generator for production of high-purity 212Pb for use in radiopharmaceuticals [J]. Journal of Nuclear Medicine, 2023, 64(1): 173‒176.
[23] Kokov K V, Egorova B V, German M N, et al. 212Pb: Production approaches and targeted therapy applications [J]. Pharmaceutics, 2022, 14(1): 189.
[24] Quelven I, Monteil J, Sage M, et al. 212Pb α-radioimmunotherapy targeting CD38 in multiple myeloma: A preclinical study [J]. Journal of Nuclear Medicine, 2020, 61(7): 1058‒1065.
[25] Stallons T A R, Saidi A, Tworowska I, et al. Preclinical investigation of 212Pb-DOTAMTATE for peptide receptor radionuclide therapy in a neuroendocrine tumor model [J]. Molecular Cancer Therapeutics, 2019, 18(5): 1012‒1021.
[26] Delpassand E S, Tworowska I, Esfandiari R, et al. Targeted α-emitter therapy with 212Pb-DOTAMTATE for the treatment of metastatic SSTR-expressing neuroendocrine tumors: First-in-humans dose-escalation clinical trial [J]. Journal of Nuclear Medicine, 2022, 63(9): 1326‒1333.
[27] Meredith R, Torgue J, Shen S, et al. Dose escalation and dosimetry of first-in-human α radioimmunotherapy with 212Pb-TCMC-trastuzumab [J]. Journal of Nuclear Medicine, 2014, 55(10): 1636‒1642.
[28] Koehler C, Sauter P F, Klasen B, et al. Genetic code expansion for site-specific labeling of antibodies with radioisotopes [J]. ACS Chemical Biology, 2023, 18(3): 443‒448.
[29] Li Y S, Li F F, Jiang F, et al. A mini-review for cancer immunotherapy: Molecular understanding of PD-1/PD-L1 pathway & translational blockade of immune checkpoints [J]. International Journal of Molecular Sciences, 2016, 17(7): 1151.
[30] Ren J Y, Xu M X, Chen J Y, et al. PET imaging facilitates antibody screening for synergistic radioimmunotherapy with a 177Lu-labeled αPD-L1 antibody [J]. Theranostics, 2021, 11(1): 304‒315.
[31] Xu K, Wang T L, Pan S B, et al. The efficacy and toxicity of mirvetuximab soravtansine, a novel antibody-drug conjugate, in the treatment of advanced or recurrent ovarian cancer: A meta-analysis [J]. Expert Review of Clinical Pharmacology, 2023, 16(11): 1141‒1152.
[32] Desai A, Abdayem P, Adjei A A, et al. Antibody-drug conjugates: A promising novel therapeutic approach in lung cancer [J]. Lung Cancer, 2022, 163: 96‒106.
[33] Wen Y, Ouyang D J, Zou Q Y, et al. A literature review of the promising future of TROP2: A potential drug therapy target [J]. Annals of Translational Medicine, 2022, 10(24): 1403.
[34] Liu X L, Deng J W, Yuan Y, et al. Advances in Trop2-targeted therapy: Novel agents and opportunities beyond breast cancer [J]. Pharmacology & Therapeutics, 2022, 239: 108296.
[35] Shen M, Liu S Q, Stoyanova T. The role of Trop2 in prostate cancer: An oncogene, biomarker, and therapeutic target [J]. American Journal of Clinical and Experimental Urology, 2021, 9(1): 73‒87.
[36] Tseng H C, Xiong W, Badeti S, et al. Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma [J]. Nature Communications, 2020, 11(1): 4810.
[37] Blakkisrud J, Løndalen A, Martinsen A C T, et al. Tumor-absorbed dose for non-hodgkin lymphoma patients treated with the anti-CD37 antibody radionuclide conjugate 177Lu-lilotomab satetraxetan [J]. Journal of Nuclear Medicine, 2017, 58(1): 48‒54.
[38] Tano H, Oroujeni M, Vorobyeva A, et al. Comparative evaluation of novel 177Lu-labeled PNA probes for affibody-mediated PNA-based pretargeting [J]. Cancers, 2021, 13(3): 500.
[39] Myrhammar A, Vorobyeva A, Westerlund K, et al. Evaluation of an antibody-PNA conjugate as a clearing agent for antibody-based PNA-mediated radionuclide pretargeting [J]. Scientific Reports, 2020, 10(1): 20777.
[40] Nejadghaderi S A, Balibegloo M, Noori M, et al. Clinical efficacy and safety of bispecific antibodies for the treatment of solid tumors: A systematic review and meta-analysis [J]. Expert Review of Anticancer Therapy, 2023, 23(3): 307‒318.
[41] Jallinoja V I J, Abbriano C H, Bhatt K, et al. Pretargeting with cucurbituril-adamantane host-guest pair in xenograft models [J]. Journal of Nuclear Medicine, 2023, 64(8): 1203‒1209.
[42] Bauer D, Carter L M, Atmane M I, et al. 212Pb-pretargeted theranostics for pancreatic cancer [J]. Journal of Nuclear Medicine, 2024, 65(1): 109‒116.
京公网安备 11010502051620号
