DEVELOPMENT OF TOOLS FOR INTERNAL RADIATION DOSIMETRY AND QUALITY MANAGEMENT IN NUCLEAR - PowerPoint Presentation

1. DEVELOPMENT OF TOOLS FOR INTERNAL RADIATION DOSIMETRY AND QUALITY MANAGEMENT IN NUCLEAR MEDICINE DR. LEONEL A. TORRESDIC-CENTIS2016WORSHOP: Physics and Applications of High Brightness Beams

2. Specification, acceptance testing, quality control and maintenance of nuclear medicine equipment.Radiation safety of patients, staff and public.Quality Improvements and Optimization of clinical studies.Quality Management Systems.Computer system management and support.Basic and Clinical Research Activities.Teaching Activities.Main Activities:MEDICAL PHYSICISTS IN NUCLEAR MEDICINE

3. DEVELOPMENT OF TOOLS FOR INTERNAL RADIATION DOSIMETRY IN NUCLEAR MEDICINE

4. CENTRE OF ISOTOPES (CENTIS)CECMEDCNSNREGULATORY AUTHORITIES:CENTRE OF MOLECULAR IMMUNOLOGY (CIM)CENTRE OF GENETIC INGENEERING AND BIOTECNOLOGY (CIGB)HOSPITALARY RADIOPHARMACY:Medical Doctors:34 FM: 24 RF: 13INTERNAL DOSIMETRY TO EVALUATE NEW RADIOPHARMACEUTICALS

5. INTERNAL DOSIMETRY TO SUPPORT THE RADIONUCLIDE THERAPYThyroid Diseases 131INET131I-MIBG, 90Y-,177Lu-péptidos(PRRT)Hepatic TumorsRadioembolization90Y-microespheresBrain Tumors90Y-,131I-, 188Re- AcMs, péptidos, etcBone Pain 89Sr, 32P, 153Sm-EDTMP, 188Re-HEDP , 90Y-HEDP, 223RaLR-RNTIA-RNTNecessityLymphomas (NHL)131I-Bexxar, 90Y-Zevalin Breast Cancer 90Y- IART

6. Limitation of traditional methodsPoor Dose-Response & Dose-Radiotoxicity correlationPatient Specific DosimetryDOSE ASSESTMENTS FROM THERAPEUTIC RADIOPHARMACEUTICALSIntroducción(3D PATIENT-SPECIFIC DOSIMETRY)

7. 3D PATIENT-SPECIFIC DOSIMETRYActivity DistributionAtenuation correctionDensit, compositionSPECT/PETCTMIRD (voxel)Convolution Monte CarloDVH, Mean Doses, Maximun DosesSegmentation3D DOSE CALCULATIONS[Gy][µCi-seg][g/cm3][Gy]Radiobiologic Parametersα/β, λeff µ, γα/β3D BED DistributionsTCPNTCPEUDCUMULATIVE ACTIVITY3D RADIOBIOLOGIC ASSESTMENTS

8. Kolbert KS, Sgouros G, Scott AM, et al. J Nucl Med. 1997;38:301–308.Osem Reconstruction (OSEM)Image Processin (MIAU)Image CorregistrationDose Claculation by Monte Carlotechniques and the kernel methods.Curve fitting at voxel level.Radiobiology analysis of data3D-ID. Implementation and evaluation ofpatient-specific three-dimensional internal dosimetry. (Memorial Sloan-Kettering Cancer Center, NY, USA)(3D-ID / 3D-RD)

9. CANCER BIOTHERAPY & RADIOPHARMACEUTICALS Volume 20, Number 1, 2005The LundADose Method for Planar Image Activity Quantification and Absorbed-Dose assessment in RNT (Lund University. Sweden)DOSIMG

10. Torres LA,Coca, MA, Batista JF et al. Nuclear Medicine Communications 2008, 29:66–75Torres LA, Coca MA, Cornejo N. Procecedings. QANTRM, Vienna, Austria. 2006. IAEA-CN-146.Coca M.A., Torres L.A. and Cornejo N. Nucleus, 2003. 33: p. 49-53.TPS-NM: Local Software Package for 3D Dose Estimations Programing Lenguajes: IDL, DelphiInternal Modules: Konvox, MCID

11. CT/MRISPECT/PETCUMULATIVE ACTIVITY CALCULATIONIMAGE COREGISTRATION¨S¨ Values Calculations (Konvox)MCID Input File (For MC Simulations)3D Dose Calculation (Coconvolution Method)Monte Carlo Simulation3D Dose Distribution Analysis (Mean Dose, Max, Min, DVH, Isodose Curves, etc) FLOWCHART(Non uniform activity in homogeneous tissue)(Non uniform activity in non-homogeneous tissue)TPS-NM: Local Software Package for 3D Dose Estimations

12. (128,128,128)(i,j,k)(0,0,0)(i+1,j,k)(h)(k)(source)(target)(0,0,0)(0,1,0)(i,j,k)(0,j,0)3D Dose Dist.MIRD FORMALISMBolch, W.E., et al. MIRD Pamphlet No. 17: “The dosimetry of ….” J Nucl Med, 1999. 40: p. 11S-36S.

13. CUMULATIVE ACTIVITYVoxel Level. . . . . . T1T2T3Tn ͚Ã x,y,z = ∫ A x,y,z (t) dt [MB-h] oA[MBq]T[Horas]T1T2T3Tnxxxx ͚Ã o,o,o = ∫ A o,o,o (t) dt o ͚Ã n,n,n = ∫ A n,n,n (t) dt o. .. .. .Bolch, W.E., et al. MIRD Pamphlet No. 17: “The dosimetry of ….” J Nucl Med, 1999. 40: p. 11S-36S.

14. A= Ao exp(-λt)Ãtumor= Ao/λtumor%IDt(h)A(t)tumorTadq=3hÃtumor Ãx,y,z-------- = --------CT tumor Cx,y,zTomographic Slices 3D of Cumulative activity Ãtumor * Cx,y,z Ãx,y,z = --------- CT tumorBolch, W.E., et al. MIRD Pamphlet No. 17: “The dosimetry of ….” J Nucl Med, 1999. 40: p. 11S-36S.CUMULATIVE ACTIVITY (Voxel Level)Hybrid Method

15. CUMULATIVE ACTIVITYVoxel LevelSPECT-SPECT

16. WEBDITE to download ¨S¨ valuesHOW ?WHERE ?WHERE ?ACCESS ?

17. “S” values Availability: KONVOXCross, W.G. et al. ¨Beta-ray dose..¨. HealthPhys, 1992. 63(2): p. 160-171.Furhang, E. et al. “A Monte Carlo ….”. Med Phys 1996. 23: p. 1523-1529.

18. CUMULATIVE ACTIVITY CALCULATIONS: STEPSPK PARAMETERS FROM THE TARGET VOLUME

19. 3D DOSE DISTRIBUTION ANALYSIS

20. 3D DOSE DISTRIBUTION ANALYSIS

21. FUNTIONAL IMAGEANATOMIC IMAGEINTERFAZMC SIMULACION3D Dose DistributionsDVHIsodose CurvesMean, Max ValuesAdvantagesNon homogeneous Tissues(MCNPx, EGSnrc, GEANT4, etc)Monte Carlo Dose Estimations: MCID module

22. Monte Carlo Dose Estimations: MCID moduleLoad the Tomopgraphic studies (CT, MRI, SPECT,PET)Image Formats: DICOM, Analyze, Interfile, MTFVOIs Selection ModuleIdentifying the tissues distribution

23. MCID VALIDATIONMCID results were compared with other dosimetric tools developed at the IEO, Italy, involving dose estimation from 3D distriburion of activities in physical phantoms (Fluka, EGS)

24. ABSOLUTE ACTIVITY QUANTIFICATIONCALIBRATED 133Ba SOURCESActivity in each rod at the time of measurement (MBq)B-A13B-B13B-C13B-D13Test 10.390.911.141.04Test 20.360.891.091.03Average0.371.101.421.30Dose Calibrator (Ba-133 setting)0.41.11.41.3Relatives differences (%)Average6.92%-0.45%-1.39%0.25%

25. CORRECTION OF FACTOR AFFECTING IMAGE QUANTIFICATIONESTIMATING ATTENUATION CORRECTION COEFFICIENTS

26. Posición(Kev)Limite inferior(Kev)Límite Superior (Kev)Dispersión Inf308289.52326.48Emisión364327.6400.4Dispersión Sup421402.05439.34INORHHADIC-CENTISINEFCORRECTION OF FACTOR AFFECTING IMAGE QUANTIFICATION

27. Development of new Tools for Activity QuantificationBREMSSTRAHLUNG RADIATION QUANTIFICATION FROM SPECTDevelopment of new codes of MCID to create the attenuation maps required by the OSEM algoriths of the Frey-Ljungberg reconstruction methods

28. 90Y Activity: 11.2 mCi4 Point Sources of 133Ba (E.Landmarks)Matriz size: 64 x 64No. Proj.:64CP: 30seg/ProjSPECT QUANTIFICATION PRELIMINARY EVALUATION

29. CLINICAL USE

30. 3 mg/ 10 mCi (6 patients)Grupo I (G-I)3mg/15 mCi (3 patients) Grupo II (G-II)Phase I Clinical Trial.Scalation StudySingle Dose per patientFor data collection, processing and analysis accordingIt was used the developed methodology. PATIENTSRIT-LR de Gliomas188Re-Nimotuzumab

31. Biokinetics StudyTPS-MN: CLINICAL USE ON THE IART THERAPY (CIC - IEO Italy)

32. Curce Fitting Parameters:Cte_A (MBq)= 271,21Cte_B (MBq)= 165,81 Landa_A (1/hr)= 0,01293 Landa_B (1/hr)= 0,26131Act_Tot_Voi (MBq) = 259MBqSensibilidad: 5779,5 c/MBqActivity: 185MBq 111In-biotin + 3.7GBq 90Y-biotin. Clearance: 93% by orineMalignant Tissue uptake: 7%A%(t) = [A1*(1-exp(-a1*t)) + A2*exp(-a2*t)]*exp(-λt) A1(%)=5.7% A2(%)=3.0% a1 = 0.1716 h^-1a2 = 0.0291 h^-1 λ = 90Y TPS-MN: CLINICAL USE ON THE IART THERAPY (CIC - IEO Italy)

33. Activity: 79mCi - 177Lu-DOTATATE WB: 0.5, 16,40 y 64 horasSPECT: 40hCorrections: Scatter, Attenuation, BackgroundTPS-MN: CLINICAL USERADIONUCLIDE THERAPY OF NET

34. Arel=M1*(exp(-t*ln2/M2)-exp(-t*ln2/M3))M1=0.015282M2=121.8hM3=0.125hArel(96h)=8.25MBqA 90Y=888 MBq (=0.4 mCi/kg*37*60 kg)A111In = 148 MBqTPS-MN: CLINICAL USEZEVALIN

35. DEVELOPMENT OF TOOLS TO SUPPORT THE ESTABLISHMENT OF QUALITY MANAGEMENT SYSTEMS IN NUCLEAR MEDICINE

36. NATIONAL PROGRAM FOR QUALITY ASSURANCE OF NUCLEAR MEDICINE INSTRUMENTSCREATION OF A NATIONAL PROTOCOL FOR QC OF NM INSTRUMENTS.PHANTOM BANK.ESTABLISMENT AND REGISTRATION OF A REGULAR COURSE ABOUT ¨QC OF NM INSTRUMENTS¨.ESTABLISHMENT OF A NATIONAL PROGRAM FOR CONDUCING EXTERNAL AUDITSCONTRIBUTION TO THE PREPARATION OF NEW REGULATIONS FOR OPTIMAL USE ON NM INSTRUMENTS(EXTERNAL AUDTS ARE BEING CARRIED OUT USING THE DEVELOPED PROGRAMS)(CECMED)

37. PreparationCorrective Actions.Continual ImprovementExternal AuditCertification/Acreditation+Regulatory RequirementPlanning and Design DocumentationImplementationManagement ReviewInternal AuditsESTABLISHING QUALITY MANAGEMENT SYSTEMS

38. Development of web applications for managing the documental systems: (QNUMED)Development of prototypes for the main documents of a QMS (e.g. Quality Manual, SOPs templates, clinical protocols, records forms, etc)Creation of a tool (spreadsheets) for automatic evaluation of internal audits based on QUANUM requirements.Development of tools for education and training in QC/QA/QM topics.(As part of the IAEA RLA6065 Project: “Strengthening Quality Assurance in Nuclear Medicine” - ARCAL CXI)QMS IN NUCLEAR MEDICINE: MAIN CONTRIBUTIONS

39. QM IN NM IN LATIN AMERICA Development of tools to support the QM ActivitiesDevelopment of a new tool to the management of the documental system in digital format (includes forms, indicator management, supporting documents, etc)Use of Free softwareDevelopment platform: DrupalWeb servidor: Apache Gestor de bases de datos: MySQL

40. QM IN NM IN LATIN AMERICA Development of tools to support the QM ActivitiesDevelopment of a new tool to the management of the documental system in digital format (includes forms, indicator management, supporting documents, etc)Use of Free softwareDevelopment platform: DrupalWeb servidor: Apache Gestor de bases de datos: MySQL

41. QM IN NM IN LATIN AMERICA Development of tools to support the QM ActivitiesDevelopment of a new tool to the management of the documental system in digital format (includes forms, indicator management, supporting documents, etc)Use of Free softwareDevelopment platform: DrupalWeb servidor: Apache Gestor de bases de datos: MySQL

42. http://nucleus.iaea.org/HHW/NuclearMedicine/QualityPractice/index.htmlTool: QUANUM Checklists (Spreadsheets)MAIN FEATURES:INCLUDE 14 PAGES WITH TO EVALUATE THE MAIN AREAS OF QMS IN NMALLOW AUTOMATIC CALCULATION OF OVERALL AND SPECIFIC SCORING5 LEVEL OF REQUIREMENT CONFORMITYDESIGNED TO SUPPORT INTERNAL AND EXTERNAL AUDITS IN NUCLEAR MEDICINE SERVICES

43. http://nucleus.iaea.org/HHW/NuclearMedicine/QualityPractice/index.htmlTool: QUANUM Checklists (Spreadsheets)MAIN FEATURES:AUTOMATIC GENERATION OF RADAR PLOT TO INTEGRAL ANALYSIS OF QM SYSTEMSTESTED COMPATIBILITY WITH:Operative Systems: Linux (Ubuntu) / Mac OSOffice Suites: LibreOffice / OpenOffice THIS TOOL HAS BEEN USED IN SEVERAL INTERNAL AND EXTERNAL QUALITY AUDITS IN NM AROUND THE WORLDDESIGNED TO SUPPORT INTERNAL AND EXTERNAL AUDITS IN NUCLEAR MEDICINE SERVICES

44. 1. Introducción. 41.1. Antecedentes. 41.2. Objetivo del documento. 61.3. Alcance . 71.4. Estructura del documento. 71.5. Consideraciones generales sobre la documentación de un SGC. 71.5.1. Manual de Calidad. 82. Guía para la confección del Manual de Calidad. 102.1. I. Portada 122.2. II. Presentación del Servicio. 132.2.1. II.1. Datos generales de la institución. 132.2.2. II.2. Estructura organizativa. 132.2.3. II.3. Funciones y responsabilidades 142.2.4. II.4. Catálogo de servicios 162.3. III. Objeto y Alcance del Manual 182.4. IV-) Política y objetivos de Calidad. 192.5. V-) Sistema de Gestión de la Calidad. 212.5.1. V.1. Requisitos generales. 212.5.2. V.2. Requisitos de la documentación 222.5.3. V.3. Manual de la calidad 222.5.4. V.4. Control de documentos 232.5.5. V.5. Control de registros 232.5.6. V.6. Alcance del sistema de gestión de la calidad 232.6. VI. Responsabilidad de la dirección. 242.6.1. VI.1 Compromiso de la dirección. 242.6.2. VI.2. Enfoque al cliente. 242.6.3. VI.3. Política de la calidad. 242.6.4. VI.4. Planificación 252.6.5. VI.5. Responsabilidad, autoridad y comunicación 252.6.6. VI.6. Revisión por la dirección 26Quality Manual Development of a prototype for the LA regionINDEX

45. 2.7. VII. Gestión y Desarrollo de Recursos. 282.7.1. VII.1. Recursos humanos. 282.7.2. VII.2. Recursos financieros. 292.7.3. VII.3. Infraestructura. 292.7.4. VII.4. Ambiente de trabajo. 292.8. VIII. Realización del Servicio de Medicina Nuclear. 312.8.1. VIII.1. Servicios Clínicos Generales. 312.8.2. VIII.2. Protección Radiológica. 322.8.3. VIII.3. Control del equipamiento. 332.8.4. VIII.4. Radiofarmacia. 332.8.5. VIII. 5. Compras. 342.9. IX. Medición, Análisis y Mejora. 362.9.1. IX.1. Satisfacción del Cliente. 362.9.2. IX.2. Auditorías Internas. 362.9.3. IX.3. Seguimiento y medición de los procesos. 372.9.4. IX.4. Control de producto no conforme. 372.9.5. IX.5. Análisis de datos 372.9.6. IX..6. Mejora continua 373. Elementos del Sistema Documental. 393.1. Procedimientos. 393.2. Ejemplos de documentos del sistema. 86Términos y definiciones. 87Referencias 94Bibliografía 96Colaboradores en la redacción y revisión. 99INDEXQuality Manual Development of a prototype for the LA region

46. TOOLS FOR EDUCATION AND TRAINING IN QC/QA/QM TOPICS.Intrinsic Flood Field UniformitySystem Flood Field UniformitySystem Planar SensitivityMaximum Count RateIntrinsic Spatial Resolution - Visual methodIntrinsic Spatial Resolution and LinearitySystem Spatial ResolutionEnergy ResolutionMultiple Window Spatial RegistrationPhysical InspectionTomographic Uniformity Center of RotationAbsolute Size of a PixelTomographic ResolutionTotal Performance.Video Total PerformanceDEVELOPMENT OF ELEARNING MODULES FOR QC/QA ON NM INSTRUMENTS

47. Place: HHAOrganizers: Center for Clinical Researches, Habana, CubaParticipants (Total): 30 National Course: “Implementation of Quality Management Systems.CUBADocumentation related to the course (Program, lectures, etc) available for other LA institutions

48. THANK YOU