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Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:

2024 08

Page:

1543-1549

Research Field:

Publishing date:

Info

Title:

The research progress of 225Ac-PSMA in the treatment of metastatic castration resistant prostate cancer

Author(s):

ZHENG Xingwang¹; LIU Zhen²; YIN Bo¹

1.Department of Urology,Shengjing Hospital of China Medical University,Liaoning Shenyang 110004,China;2.Department of Urology,the People's Hospital of Liaoning Province,Liaoning Shenyang 110067,China.

Keywords:

metastatic castration resistant prostate cancer; radionuclide therapy; Actinium-225

PACS:

R737.25

DOI:

10.3969/j.issn.1672-4992.2024.08.031

Abstract:

Prostate cancer£¨PCa£© is the second highest incidence among men in the world,and it has gradually become the main cause of cancer death among males in China.Metastatic castration resistant prostate cancer (mCRPC) is the terminal stage of prostate cancer progression,which is arduous to treat.Previous treatments include novel hormone therapy (NHT),chemotherapy,PARP inhibitor therapy,immune and targeted therapy,radionuclide therapy and so on.Prostate specific membrane antigen (PSMA) is a popular target for radionuclide therapy.The ¦Â-nuclide 177Lu has been approved by the U.S.Food and Drug Administration (FDA) for the treatment of PSMA-positive mCRPC patients.¦Á radionuclide 223Ra has gradually entered the field of vision of Chinese researches and is recommended for the treatment of patients with bone metastases.225Ac shows significant anti-tumor activity in the treatment of mCRPC,and has the characteristics of good effect and relatively high safety,which has extensive prospects.This article will review the research progress of actinium (Actinium-225,225Ac),a new radionuclide targeted on PSMA,which is rarely reported in China,from the aspects of current status,efficacy analysis and toxic effects,etc.,in order to help clinical workers to grasp the frontier trends of radionuclide treatment of prostate cancer and assist their scientific decision-making.Unfortunately,the existing studies are basically single-center retrospective studies,and there is still a lack of international multi-center,prospective cohort studies and clinical trials.The main side effects of 225Ac treatment are xerostomia,nephrotoxicity and hematological toxicity (such as anemia,leukopenia and thrombocytopenia).The researchers' understanding of the toxicity of 225Ac and its side reaction mechanism is still not comprehensive,and the research of related combined sequential therapy is not deep enough.So there is still numerous follow-up research work to be completed before it is officially approved for clinical patients.

References:

£Û1£Ý SUNG H,FERLAY J,SIEGEL RL,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries£ÛJ£Ý.CA:A Cancer Journal for Clinicians,2021,71(3):209-249.
£Û2£Ý XIA C,DONG X,LI H,et al.Cancer statistics in China and United States,2022:profiles,trends,and determinants£ÛJ£Ý.Chinese Medical Journal,2022,135(5):584-590.
£Û3£Ý SAAD F,APRIKIAN A,FINELLI A,et al.2022 Canadian Urological Association (CUA)-Canadian Uro Oncology Group (CUOG) guideline:Management of castration-resistant prostate cancer (CRPC)£ÛJ£Ý.Canadian Urological Association Journal,2022,16(11):E506-E515.
£Û4£Ý SATHEKGE MM,BRUCHERTSEIFER F,VORSTER M,et al.Global experience with PSMA-based alpha therapy in prostate cancer£ÛJ£Ý.European Journal of Nuclear Medicine and Molecular Imaging,2021,49(1):30-46.
£Û5£Ý DAVIS MI,BENNETT MJ,THOMAS LM,et al.Crystal structure of prostate-specific membrane antigen,a tumor marker and peptidase£ÛJ£Ý.Proceedings of the National Academy of Sciences of the United States of America,2005,102(17):5981-5986.
£Û6£Ý CHANG SS,O' KEEFE DS,BACICH DJ,et al.Prostate-specific membrane antigen is produced in tumor-associated neovasculature£ÛJ£Ý.Clinical Cancer Research,1999,5(10):2674-2681.
£Û7£Ý CZERWINSKA M,BILEWICZ A,KRUSZEWSKI M,et al.Targeted radionuclide therapy of prostate cancer-from basic research to clinical perspectives£ÛJ£Ý.Molecules (Basel,Switzerland),2020,25(7):E1743.
£Û8£Ý »Æº£,ÀµÒåÃ÷,ºÎÍú,µÈ.PSMA¶ÔJNK/SAPKͨ·µÄ¼¤»î¼°¶ÔÇ°ÁÐÏÙ°©Ï¸°ûµòÍöµÄµ÷¿Ø£ÛJ£Ý.Öйú²¡ÀíÉúÀíÔÓÖ¾,2014,30(05):785-791. HUANG H,LAI YM£¬HE W,et al.PSMA activates JNK/SAPK pathway and regulates apoptosis of prostate cancer cells £ÛJ£Ý.Chinese Journal of Pathophysiology,2014,30(05):785-791.
£Û9£Ý CURRENT K,MEYER C,MAGYAR C,et al.Investigating PSMA-targeted radioligand therapy efficacy as a function of cellular PSMA levels and intra-tumoral PSMA heterogeneity£ÛJ£Ý.Clinical Cancer Research,2020,26(12):2946-2955.
£Û10£Ý RUIGROK EAM,VAN VLIET N,DALM SU,et al.Extensive preclinical evaluation of lutetium-177-labeled PSMA-specific tracers for prostate cancer radionuclide therapy£ÛJ£Ý.European Journal of Nuclear Medicine and Molecular Imaging,2021,48(5):1339-1350.
£Û11£Ý ZECHMANN CM,AFSHAR-OROMIEH A,ARMOR T,et al.Radiation dosimetry and first therapy results with a 124I/131I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy£ÛJ£Ý.European Journal of Nuclear Medicine and Molecular Imaging,2014,41(7):1280-1292.
£Û12£Ý AFSHAR-OROMIEH A,HABERKORN U,ZECHMANN C,et al.Repeated PSMA-targeting radioligand therapy of metastatic prostate cancer with 131I-MIP-1095£ÛJ£Ý.European Journal of Nuclear Medicine and Molecular Imaging,2017,44(6):950-959.
£Û13£Ý M¦aLLER C,UMBRICHT CA,GRACHEVA N,et al.Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer£ÛJ£Ý.European Journal of Nuclear Medicine and Molecular Imaging,2019,46(9):1919-1930.
£Û14£Ý SARTOR O,DE BONO J,CHI KN,et al.Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer£ÛJ£Ý.The New England Journal of Medicine,2021,385(12):1091-1103.
£Û15£Ý NONNEKENS J,CHATALIC KLS,MOLKENBOER-KUENEN JDM,et al.213Bi-labeled prostate-specific membrane antigen-targeting agents induce DNA double-strand breaks in prostate cancer xenografts£ÛJ£Ý.Cancer Biotherapy & Radiopharmaceuticals,2017,32(2):67-73.
£Û16£Ý PARKER C,NILSSON S,HEINRICH D,et al.Alpha emitter radium-223 and survival in metastatic prostate cancer£ÛJ£Ý.The New England Journal of Medicine,2013,369(3):213-223.
£Û17£Ý HAMMER S,HAGEMANN UB,ZITZMANN-KOLBE S,et al.Preclinical efficacy of a PSMA-targeted thorium-227 conjugate (PSMA-TTC),a targeted alpha therapy for prostate cancer£ÛJ£Ý.Clinical Cancer Research,2020,26(8):1985-1996.
£Û18£Ý SUOMINEN MI,FAGERLUND KM,RISSANEN JP,et al.Radium-223 inhibits osseous prostate cancer growth by dual targeting of cancer cells and bone microenvironment in mouse models£ÛJ£Ý.Clinical Cancer Research,2017,23(15):4335-4346.
£Û19£Ý HOSKIN P,SARTOR O,O' SULLIVAN JM,et al.Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases,with or without previous docetaxel use:a prespecified subgroup analysis from the randomised,double-blind,phase 3 ALSYMPCA trial£ÛJ£Ý.The Lancet Oncology,2014,15(12):1397-1406.
£Û20£Ý ÖйúÒ½ÁƱ£½¡¹ú¼Ê´Ù½ø½»Á÷»áÃÚÄò½¡¿µ´Ù½ø·Ö»á.¹ÇתÒÆÐÔÈ¥ÊƵֿ¹ÐÔÇ°ÁÐÏÙ°©223RaºËËØÖÎÁÆ°²È«¹²Ê¶£ÛJ£Ý.ÏÖ´úÃÚÄòÍâ¿ÆÔÓÖ¾,2022,27(05):373-380,385. China International Healthcare Promotion and Exchange Association Urology Health Promotion Branch.Safety consensus statement on Radium 223 dichloride for the treatment of bone metastatic castration-resistant prostate cancer £ÛJ£Ý.Journal of Modern Urology,2022,27(05):373-380,385.
£Û21£Ý HOFMAN MS,EMMETT L,SANDHU S,et al.£Û177Lu£ÝLu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP):a randomised,open-label,phase 2 trial£ÛJ£Ý.Lancet (London,England),2021,397(10276):797-804.
£Û22£Ý RUIGROK EAM,TAMBORINO G,DE BLOIS E,et al.In vitro dose effect relationships of actinium-225- and lutetium-177-labeled PSMA-I&T£ÛJ£Ý.European Journal of Nuclear Medicine and Molecular Imaging,2022,49(11):3627-3638.
£Û23£Ý LAWAL IO,MORGENSTERN A,VORSTER M,et al.Hematologic toxicity profile and efficacy of £Û225Ac£ÝAc-PSMA-617 ¦Á-radioligand therapy of patients with extensive skeletal metastases of castration-resistant prostate cancer£ÛJ£Ý.European Journal of Nuclear Medicine and Molecular Imaging,2022,49(10):3581-3592.
£Û24£Ý KRATOCHWIL C,BRUCHERTSEIFER F,GIESEL FL,et al.225Ac-PSMA-617 for PSMA-targeted ¦Á-radiation therapy of metastatic castration-resistant prostate cancer£ÛJ£Ý.Journal of Nuclear Medicine,2016,57(12):1941-1944.
£Û25£Ý SCHER HI,MORRIS MJ,STADLER WM,et al.Trial design and objectives for castration-resistant prostate cancer:updated recommendations from the prostate cancer clinical trials working group 3£ÛJ£Ý.Journal of Clinical Oncology,2016,34(12):1402-1418.
£Û26£Ý HOFMAN MS,LAWRENTSCHUK N,FRANCIS RJ,et al.Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA):a prospective,randomised,multicentre study£ÛJ£Ý.Lancet (London,England),2020,395(10231):1208-1216.
£Û27£Ý SATHEKGE M,BRUCHERTSEIFER F,KNOESEN O,et al.225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer:a pilot study£ÛJ£Ý.European Journal of Nuclear Medicine and Molecular Imaging,2019,46(1):129-138.
£Û28£Ý FEUERECKER B,TAUBER R,KNORR K,et al.Activity and adverse events of actinium-225-PSMA-617 in advanced metastatic castration-resistant prostate cancer after failure of lutetium-177-PSMA£ÛJ£Ý.European Urology,2021,79(3):343-350.
£Û29£Ý YADAV MP,BALLAL S,SAHOO RK,et al.Efficacy and safety of 225Ac-PSMA-617 targeted alpha therapy in metastatic castration-resistant prostate cancer patients£ÛJ£Ý.Theranostics,2020,10(20):9364-9377.
£Û30£Ý SATHEKGE M,BRUCHERTSEIFER F,VORSTER M,et al.Predictors of overall and disease-free survival in metastatic castration-resistant prostate cancer patients receiving 225Ac-PSMA-617 radioligand therapy£ÛJ£Ý.Journal of Nuclear Medicine,2020,61(1):62-69.
£Û31£Ý ROSAR F,HAU F,BARTHOLOM¦F M,et al.Molecular imaging and biochemical response assessment after a single cycle of £Û225Ac£ÝAc-PSMA-617/£Û177Lu£ÝLu-PSMA-617 tandem therapy in mCRPC patients who have progressed on £Û177Lu£ÝLu-PSMA-617 monotherapy£ÛJ£Ý.Theranostics,2021,11(9):4050-4060.
£Û32£Ý KRATOCHWIL C,BRUCHERTSEIFER F,RATHKE H,et al.Targeted ¦Á-therapy of metastatic castration-resistant prostate cancer with 225Ac-PSMA-617:Swimmer-plot analysis suggests efficacy regarding duration of tumor control£ÛJ£Ý.Journal of Nuclear Medicine,2018,59(5):795-802.
£Û33£Ý VAN DER DOELEN MJ,MEHRA N,VAN OORT IM,et al.Clinical outcomes and molecular profiling of advanced metastatic castration-resistant prostate cancer patients treated with 225Ac-PSMA-617 targeted alpha-radiation therapy£ÛJ£Ý.Urologic Oncology,2021,39(10):729.e7-729.e16.
£Û34£Ý SATAPATHY S,MITTAL BR,SOOD A,et al.Health-related quality-of-life outcomes with actinium-225-prostate-specific membrane antigen-617 therapy in patients with heavily pretreated metastatic castration-resistant prostate cancer£ÛJ£Ý.Indian Journal of Nuclear Medicine,2020,35(4):299-304.
£Û35£Ý KLEIN NULENT TJW,VALSTAR MH,DE KEIZER B,et al.Physiologic distribution of PSMA-ligand in salivary glands and seromucous glands of the head and neck on PET/CT£ÛJ£Ý.Oral Surgery,Oral Medicine,Oral Pathology and Oral Radiology,2018,125(5):478-486.
£Û36£Ý TROYER JK,BECKETT ML,WRIGHT GL.Detection and characterization of the prostate-specific membrane antigen (PSMA) in tissue extracts and body fluids£ÛJ£Ý.International Journal of Cancer,1995,62(5):552-558.
£Û37£Ý SATAPATHY S,SOOD A,DAS CK,et al.Evolving role of 225Ac-PSMA radioligand therapy in metastatic castration-resistant prostate cancer-a systematic review and meta-analysis£ÛJ£Ý.Prostate Cancer and Prostatic Diseases,2021,24(3):880-890.
£Û38£Ý KRATOCHWIL C,BRUCHERTSEIFER F,RATHKE H,et al.Targeted ¦Á-therapy of metastatic castration-resistant prostate cancer with 225Ac-PSMA-617:dosimetry estimate and empiric dose finding£ÛJ£Ý.Journal of Nuclear Medicine,2017,58(10):1624-1631.
£Û39£Ý ¸µÎÄ»á,ÐìæÃæÃ,Áõ»áÅÊ,µÈ.225Ac/177Lu-PSMA-617ÖÎÁÆÇ°ÁÐÏÙ°©¼Ì·¢ÍÙÒºÏÙËðÉ˼°±£»¤µÄÑо¿½øÕ¹£ÛJ£Ý.ÖлªºËҽѧÓë·Ö×ÓÓ°ÏñÔÓÖ¾,2022,42(10):628-632. FU WH,XU TT,LIU HP,et al.Research progress of salivary glands injury secondary to 225Ac/177Lu-PSMA-617 in the treatment of prostate cancer and its protection£ÛJ£Ý.Chinese Journal of Nuclear Medicine and Molecular Imaging,2022,42(10):628-632.
£Û40£Ý RATHKE H,KRATOCHWIL C,HOHENBERGER R,et al.Initial clinical experience performing sialendoscopy for salivary gland protection in patients undergoing 225Ac-PSMA-617 RLT£ÛJ£Ý.European Journal of Nuclear Medicine and Molecular Imaging,2019,46(1):139-147.
£Û41£Ý MOHAN V,BRUIN NM,TESSELAAR MET,et al.Muscarinic inhibition of salivary glands with glycopyrronium bromide does not reduce the uptake of PSMA-ligands or radioiodine£ÛJ£Ý.EJNMMI research,2021,11(1):25.
£Û42£Ý TRANEL J,FENG FY,JAMES SS,et al.Effect of microdistribution of alpha and beta-emitters in targeted radionuclide therapies on delivered absorbed dose in a GATE model of bone marrow£ÛJ£Ý.Physics in Medicine and Biology,2021,66(3):035016.
£Û43£Ý PELLETIER K,C¦YT¦I G,FALLAH-RAD N,et al.CKD after 225Ac-PSMA617 therapy in patients with metastatic prostate cancer£ÛJ£Ý.Kidney International Reports,2020,6(3):853-856.
£Û44£Ý ¹Ëΰ½Ü,ÖìÒ«.2022°æ¡¶CSCOÇ°ÁÐÏÙ°©ÕïÁÆÖ¸ÄÏ¡·¸üÐÂÒªµã½â¶Á£ÛJ£Ý.ÖйúÖ×ÁöÍâ¿ÆÔÓÖ¾,2022,14(3):224-232. GU WJ,ZHU Y.Update and interpretation of the 2022 Guidelines for the Diagnosis and Treatment of Prostate Cancer by Chinese Society of Clinical Oncology (CSCO) £ÛJ£Ý.Chinese Journal of Surgical Oncology,2022,14(3):224-232.

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