1. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
1
Therapeutic Effects of Beta Radiation inTherapeutic Effects of Beta Radiation in
Nuclear MedicineNuclear Medicine
Miloš BERAN
Radiopharmaceutical Department
Nuclear Physics Institute
Czech Academy of Sciences
Řež near Prague
milber@atlas.cz
2. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
2
General characteristics of nuclear medicineGeneral characteristics of nuclear medicine
interdisciplinary positioninterdisciplinary position
3. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
3
Classification ofClassification of ββ--radionuclides for use in nuclear medicineradionuclides for use in nuclear medicine
from J. Zweit: Phys Med Biolfrom J. Zweit: Phys Med Biol 4141 (1996) 1905(1996) 1905--19141914
5. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
5
Low energy electrons (Auger electrons) emittingLow energy electrons (Auger electrons) emitting
radionuclidesradionuclides
6. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
6
ββ--particles soft tissue range of some radionuclidesparticles soft tissue range of some radionuclides
in radionuclide therapyin radionuclide therapy
J. Carlsson et al., Radiotherapy and Oncology 66 (2003) 107–
117
7. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
7
Therapeutic use of someTherapeutic use of some ββ--radionuclidesradionuclides
J. Zweit: Phys Med Biol 41 (1996) 1905-1914
8. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
8
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 tumour
Radiosynoviorthesis (therapy of arthritic joint diseases) with
suspensions 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 like
monoclonal antibodies (labelled, e.g., with „carrier free“ 90Y)
against disseminated cancer cells and metastases
9. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
9
Vascularization of solid tumoursVascularization of solid tumours
Mean diameter of radioactive particles for clogging (embolization) and
necrotization of blood capillaries is about 40 µm
10. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
10
166Ho Poly Lactic Acid (PLA) microspheres
Single 166HoPLA microsphere in normal liver
parenchyma (A) and cluster of microspheres
in tumour tissue (B)
F.Nijsen: Eur J Nucl Med (2001) 28: 743-749
11. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
11
IntraIntra--arterial embolization of head and neck cancer witharterial embolization of head and neck cancer with
166166
Ho poly(LHo poly(L--lactic)acid microsphereslactic)acid microspheres
R.J.J. van Es et all: Int J Maxillofac Surg 2001; 30: 407-413
12. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
12
Characteristics of various radioisotopes for use inCharacteristics of various radioisotopes for use in
radiosynoviorthesisradiosynoviorthesis
Radionuclide Half life (days) Radiation Mean range in tissue
( mm )
198Au 2.7 β and γ 1.2
90Y 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
13. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
13
Typical radionuclide carriers for radiosynoviorthesisTypical radionuclide carriers for radiosynoviorthesis
Radionuclides
Colloids
Suspensions
(ideal particle size 2-10 µm)
186Re
90Y
169Er
166Ho
Sulphide
Citrate
Silicate
Hydroxyapatite particles
Ferrihydroxy
macroaggregates
Boromacroaggregates
14. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
14
Principle of radiation effect in radiosynoviorthesis
A – Radioactive particles (yellow stars) are phagocytosed with proliferating
synoviocytes (pink) in an inflammed hypertrophic synovia (red)
B – Necrotized synovial membrane
Blue upper layer (cartilage) should stay unaffected
P.Schneider et all: J Nucl Med 2005; 46: 48S-54S
15. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
15
OverallOverall 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
16. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
16
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.
21. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
21
Most expressed antigens on BMost expressed antigens on B--Cell NonCell Non--Hodgkin LymphomaHodgkin 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
22. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
22
First radiopharmaceuticals approved forFirst radiopharmaceuticals approved for
radioimmunnotherapy of Nonradioimmunnotherapy of Non--Hodgkin LymphomaHodgkin Lymphoma
Radiolabelled
mAb
(trade name)
Producer
(Supplier)
Approving
Authority
Date of
Registration
Biogen IDEC
Inc.
U.S., FDA February 2002
Schering AG EU, EMEA January 2004
131I-Tositumomab
(Bexxar)
GlaxoSmith
Kline Inc.
U.S., FDA June 2003
111In/90Y-
Ibritumomab
tiuxetan
(Zevalin)
23. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
23
BB--cell Noncell Non--Hodgkin Lymphoma treatmentHodgkin Lymphoma treatment
with ZEVALIN (PETwith ZEVALIN (PET--imaging)imaging)
http://www.queenspetcenter.com/brochure/
HQ4101_casestudy_03.pdf
24. M.Beran
3-rd International Summer Student
School, July 2005, Dubna-Ratmino
24
Comparison of Therapeutic Response of BComparison of Therapeutic Response of B--cell Noncell Non--HodgkinsHodgkins
Lymphoma to Immunnotherapy (Rituxan) andLymphoma to Immunnotherapy (Rituxan) and
Radioimmunnotherapy (Zevalin)Radioimmunnotherapy (Zevalin)
Response
Ibritumomab
tiuxetan
(Zevalin) n = 73
Rituximab
(Rituxan)
n = 70
P-value
Complete Response 30 % 16 % 0.002
Overall Response
(Complete+Partial) 80 % 56 % 0.040
Comment : Clinical Trials, n= number of patients
