Aleena CrisLivingston: Alpha Radionuclide Therapy in Prostate Cancer скачать в хорошем качестве

Aleena CrisLivingston: Alpha Radionuclide Therapy in Prostate Cancer

Masters Proposal presentation: Targeted Alpha Particle Radionuclide Therapy in Prostate Cancer: A Systematic Review of Therapeutic Potential, Biomarkers and Future Directions By: Aleena CrisLivingston Aims Prostate cancer(PCa)continuestoposeasubstantialglobalhealthchallenge,particularlyinits advanced,metastaticforms.Despitesignificanttherapeuticadvancementsinandrogenreceptor pathwayinhibitors,chemotherapyandmorerecently, β-emitting radioligandtherapiessuch as 177Lu-PSMA haveexpandedtreatmentoptions,themajorityofpatientswithmetastatic castration-resistantprostatecancer(mCRPC)ultimatelyprogress.Thishighlightsthepressing need formorepotentanddurabletherapeuticstrategies [10][22]. Prostate-specificmembraneantigen(PSMA)representsawell-establishedmoleculartargetdueto its highexpressioninadvancedprostatecanceranditslimitedexpressioninnormaltissues [35]. β-emitting PSMA-targetedradioligandtherapyhasdemonstratedclinicalbenefitnotably 177Lu- PSMA-617 hasachievedFoodandDrugAdministration(FDA)approvalforPSMA-positive mCRPC, demonstratingimprovedprogression-freeandoverallsurvivalinpivotaltrialslike VISION [22] but limitationspersist,includingreducedefficacyinpatientswithlargetumour burdens, heterogeneousPSMAexpression,ortreatment-resistantdisease.Furthermore,the relativelylongpathlengthof β-particles maycontributetooff-targeteffectsandlimitthe precision oftumourcelleradication [35]. Alpha-emitting radionuclidesprovideapromisingalternative.Theiruniqueradiobiological profile characterisedbyhighlinearenergytransfer(LET)andashorttissuepenetrationrange of approximately50–100 μm enableshighlylocalised,potentcytotoxicitythroughclustered, irreparable DNAdouble-strandbreaks.Thismechanismofferssuperiortumourcellkillwhile largely sparingadjacentnormaltissues.Earlyclinicaldata,particularlywith 225Ac-PSMA, have demonstrated remarkableprostate-specificantigen(PSA)responseratesanddurabledisease control,includinginpatientswhohadprogressedfollowing 177Lu-PSMA therapy [13][23]. These findings highlightthepotentialofalphaparticleradionuclidetherapytoovercomekeylimitations of β-emitters andredefinetherapeuticoutcomesinadvancedprostatecancer. The primarygoalsofthisliteraturerevieware: • Tosystematicallyreviewpreclinicalstudiesandclinicaltrials(bothcompletedandongoing) evaluatingalpha-emittingradiopharmaceuticalsinprostatecancer. • Tosummarisethetherapeuticpotentialofalpha-emittingradiopharmaceuticalsforpatients with advanced,prostatecancer. • Toidentifyclinicalandimagingbiomarkersthatserveaspredictorsoftreatmentresponseand patientoutcomes. • Toassessthecurrentgapsandbarrierstoclinicaladoptionanddeterminewhatiscurrently lackingforthetherapytotransitionintoroutinestandardclinicalpractice. • Toproposefuturedirectionsandrecommendationsforadvancingresearch,optimizingclinical implementation,andpotentialintegrationofalphaparticleradionuclidetherapyinprostate cancer whilealsoaddressingthecriticalneedfordevelopinginfrastructureandsustainable. radionuclidesupplychainstoensurereliableglobalaccesstoalpha-emittingradiopharmaceuti- cals. For more information visit our: Website: https://www.uwamedicalphysics.org Weblog: http://www.uwamedicalphysics.com Facebook:   / groups   Instagram:   / uwa_medical_physics   LinkedIn:   / medical-physics-uwa-11979b379   Twitter: @MedicalUwa YouTube Channel:    / @medicalphysicsuwa   =========================