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M.Beran 3-rd International Summer Student School, July 2005, Dubna-Ratmino 1
Therapeutic Effects of Beta Radiation in Therapeutic Effects of Beta Radiation in Nuclear MedicineNuclear Medicine
Miloš BERANRadiopharmaceutical Department
Nuclear Physics InstituteCzech Academy of Sciences
Řež near Prague
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General characteristics of nuclear medicine General characteristics of nuclear medicine interdisciplinary positioninterdisciplinary position
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Classification of Classification of ββ--radionuclides for use in nuclear medicineradionuclides for use in nuclear medicinefrom J. Zweit: Phys Med Biol from J. Zweit: Phys Med Biol 41 41 (1996) 1905(1996) 1905--19141914
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M.Beran 3-rd International Summer Student School, July 2005, Dubna-Ratmino 5
Low energy electrons (Auger electrons) emittingLow energy electrons (Auger electrons) emittingradionuclidesradionuclides
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ββ--particles soft tissue range of some radionuclides particles soft tissue range of some radionuclides in radionuclide therapyin radionuclide therapy
J. Carlsson et al., Radiotherapy and Oncology 66 (2003) 107–117
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Therapeutic use of some Therapeutic use of some ββ--radionuclidesradionuclides
J. Zweit: Phys Med Biol 41 (1996) 1905-1914
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Classification of radionuclide therapyClassification of radionuclide therapy
Embolization and necrotization of localized solid tumours• Intra-arterial application of radionuclide-bearing (90Y,
166Ho,…) microspheres (glass, resin, polylactic acid, etc.)• Injection of gel-formating labelled sol (e.g. 166Ho chitosan)
into tumourRadiosynoviorthesis (therapy of arthritic joint diseases) withsuspensions of insoluble radionuclide compounds (90Y citrate colloid,166Ho boromacroaggregates, ferric hydroxide macro-aggregates)Targeted radionuclide therapy using biomolecules• Palliative therapy of bone metastases with 89Sr chloride,
153Sm,186Re phosphonates• Radioimmunnotherapy with „smart“ biomolecules likemonoclonal antibodies (labelled, e.g., with „carrier free“ 90Y)against disseminated cancer cells and metastases
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Vascularization of solid tumoursVascularization of solid tumours
Mean diameter of radioactive particles for clogging (embolization) and necrotization of blood capillaries is about 40 µm
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166Ho Poly Lactic Acid (PLA) microspheres
Single 166HoPLA microsphere in normal liverparenchyma (A) and cluster of microspheres
in tumour tissue (B)
F.Nijsen: Eur J Nucl Med (2001) 28: 743-749
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IntraIntra--arterial embolization of head and neck cancer witharterial embolization of head and neck cancer with166166Ho poly(LHo poly(L--lactic)acid microsphereslactic)acid microspheres
R.J.J. van Es et all: Int J Maxillofac Surg 2001; 30: 407-413
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Characteristics of various radioisotopes for use in Characteristics of various radioisotopes for use in radiosynoviorthesisradiosynoviorthesis
Radionuclide Half life (days) Radiation Mean range in tissue( mm )
198Au 2.7 β and γ 1.290Y 2.7 β 3.9 (Knee)
166Ho 1.1 β and γ 3.2 (Knee)169Er 9.5 β 0.3 (Fingers)186Re 3.7 β and γ 1.2 (Elbow)
32P 14.3 β 2.6
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Typical radionuclide carriers for radiosynoviorthesisTypical radionuclide carriers for radiosynoviorthesis
Radionuclides ColloidsSuspensions
(ideal particle size 2-10 µm)186Re
90Y
169Er
166Ho
Sulphide
Citrate
Silicate
Hydroxyapatite particles
Ferrihydroxy macroaggregates
Boromacroaggregates
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Principle of radiation effect in radiosynoviorthesis
A – Radioactive particles (yellow stars) are phagocytosed with proliferatingsynoviocytes (pink) in an inflammed hypertrophic synovia (red)
B – Necrotized synovial membraneBlue upper layer (cartilage) should stay unaffected
P.Schneider et all: J Nucl Med 2005; 46: 48S-54S
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Overall Overall Success Rates for Radiosynovectomy of Different JointsSuccess Rates for Radiosynovectomy of Different Joints
Joint No. of treated patients
Success rate (%)6 mo 1 y 2 y
Knee 196 77 66 73
Shoulder 56 62 65 54
Elbow 60 51 50 50
Wrist 202 79 67 50
MCP 208 54 38 44
PIP 164 53 47 39
Hip 14 43 40 44
Ankle 58 76 100 96
Total 958 66 58 54
MCP = metacarpophalangeal; PIP = proximal interphalangeal
P.Schneider et all: J Nucl Med 2005; 46: 48S-54S
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Various biomolecules suitable as radionuclide carriersVarious biomolecules suitable as radionuclide carriers
Several different types of substances have been tried for radionuclide therapy. Examples are radioactive ions (e.g. Sr-89), low molecular weight drugs (e.g. I-131-MIBG), peptides (e.g. In-111-octreotide) and several radiolabelled macromolecular substances such as antibody fragments, various proteins, intact antibodies or antibody based conjugates and liposomes. These substances cover, as indicated, a molecular weight (MW) range of several orders of magnitude. The radionuclides are indicated as stars.
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Figure 1. Radioisotope crossfire
Vose, J. M. Oncologist 2004;9:160-172
Copyright ©2004 AlphaMed Press
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Figure 1. The HER (erb) gene family
Ross, J. S. et al. Oncologist 2003;8:307-325
Copyright ©2003 AlphaMed Press
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Figure 4. Simultaneous HER-2/neu gene amplification and protein overexpression determination
Ross, J. S. et al. Oncologist 2003;8:307-325
Copyright ©2003 AlphaMed Press
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Figure 1. Areas of potential therapeutic intervention
Nahta, R. et al. Oncologist 2003;8:5-17
Copyright ©2003 AlphaMed Press
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Most expressed antigens on BMost expressed antigens on B--Cell NonCell Non--Hodgkin Lymphoma Hodgkin Lymphoma with corresponding monoclonal antibodies (with corresponding monoclonal antibodies (mAbmAbs)s)
Target antigen Unconjugated mAb
Generic name (trade name)
Radiolabelled mAb(trade name)
B1 Tositumomab 131I-Tositumomab (Bexxar)
2B8 Ibritumomab 111In/90Y-Ibritumomab tiuxetan (Zevalin)
C2B8 Rituximab(Rituxan)
Epratuzumab (Lymphocide)
131I-Epratuzumab
111In/90Y-Epratuzumab
186Re-Epratuzumab
CD 22 hLL2
CD 20
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First radiopharmaceuticals approved for First radiopharmaceuticals approved for radioimmunnotherapy of Nonradioimmunnotherapy of Non--Hodgkin LymphomaHodgkin Lymphoma
Radiolabelled mAb
(trade name)
Producer (Supplier)
Approving Authority
Date of Registration
Biogen IDECInc.
U.S., FDA February 2002
Schering AG EU, EMEA January 2004
131I-Tositumomab (Bexxar)
GlaxoSmithKline Inc.
U.S., FDA June 2003
111In/90Y-Ibritumomab
tiuxetan (Zevalin)
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BB--cell Noncell Non--Hodgkin Lymphoma treatmentHodgkin Lymphoma treatmentwith ZEVALIN (PETwith ZEVALIN (PET--imaging)imaging)
http://www.queenspetcenter.com/brochure/HQ4101_casestudy_03.pdf
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Comparison of Therapeutic Response of BComparison of Therapeutic Response of B--cell Noncell Non--Hodgkins Hodgkins Lymphoma to Immunnotherapy (Rituxan) and Lymphoma to Immunnotherapy (Rituxan) and
Radioimmunnotherapy (Zevalin)Radioimmunnotherapy (Zevalin)
ResponseIbritumomab
tiuxetan (Zevalin) n = 73
Rituximab (Rituxan)
n = 70P-value
Complete Response 30 % 16 % 0.002
Overall Response(Complete+Partial) 80 % 56 % 0.040
Comment : Clinical Trials, n= number of patients