radiopharmaceuticals františek melichar uk 3. lf praha
Post on 25-Dec-2015
224 Views
Preview:
TRANSCRIPT
RadiopharmaceuticalsScope of Presentation
• Basic information
• Diagnostic radiopharmaceuticals
– SPECT,
– PET
• Therapeutic radiopharmaceuticals
– palliative radiopharmaceuitcals
– Immunotherapeutic radiopharmaceuticals
– radiation synovectomy
František MelicharFrantišek Melichar
Radiopharmaceuticals
A radiopharmaceutical is
a radioactive compound used for the diagnosis and therapeutic treatment
of human diseases
Radiofarmaceuticals
Has two components :
•radionuclide
•pharmaceutical
proteins, Mab, inorganic, organic compounds
Radiopharmaceuticals designing
First chosen is on basis of its preferential localization in given
organ
or
its participation in the physiologic function of the organ
Ideal radiopharmaceutical
•Easy availability
•Shorf effective Half-Life
•Particle Emission
•Decay by Electron Capture or Isomeric Transition
•High Target-to Nontarget Activity Ratio
Radiopharmaceuticals
Radioactive element - 133Xe
Labeled compounds - 131I iodinated proteins
99mTc labeled compounds
[18F]FDG
Radiopharmaceuticals
Radiopharmaceuticals usually have no pharmacologic effect, because in
most cases they are used in trace quantities
Differ from conventional drugs
but they should be sterile and pyrogen free
Easy availability (1)
Nuclear reactor (n,p), (n,)A
ZX (n,) A+1 ZX
98Mo (n,) 99Mo 99mTc
Particle accelerators68Zn (p,2n) 67Ga
203Tl (p,3n) 201Pb +or EC 201Tl
Easy availability (2)Starting material and product have diferent
chemical identities
Enriched target
Secondary source
Generator of radionuclides99Mo/99mTc, 113Sn/113mIn, 81Rb/81mKr,82Sr/82Rb,
90Sr/90Y,68Ge/68Ga
Short Effective Half-Life
Physical half-life TP , t1/2
p=0,693/Tp - decay constant
Biologic half-life Tb
b=0,693/Tb
Effective half-life Te
e= p+ b
1/Te=1/Tp +1/Tb
Particle Emission
Diagnostic purpose -undesirable
Therapeutic purpose - ,Radiation damage of abnormal cells
High Target-to Nontarget Activity Ratio
To provide maximum efficacy in
the diagnosis (therapy)
and minimum radiation dose to the patient
Factors Influencing the Design of New Radiopharmaceuticals (1)
Compatibility-incorporation radionuclide into the molecule 111In-DTPA
Stechiometry- concentration 99mTc approx. 10-9 mol/l
Charge of the Molecule
Size of Molecule
Factors Influencing the Design of New Radiopharmaceuticals (2)
Protein Binding
Solubility
Stability
Biodistribution
Type of radiopharmaceutical for diagnostic and therapy
• Parenteral pharmaceuticals (solutions or colloid suspenses),
• peroral pharmaceuticals
• inhalation pharmaceuticals
• topic pharmaceuticals
© J.Lepej, ONM BB Slovakia
153SmSamárium
- 103 keV46,7 h
186ReRénium
- 137 keV3,78 d
131 IJód
- 158 keV8,02 d
Ac
HB FC N O Ne
Na Mg Al ClSi P S ArGa BrGe As Se KrK Ca
Rb Sr In ISn Sb Te XeTl AtPb Bi Po RnCs Ba
Fr Ra
He
Cu ZnCo NiMn FeV CrSc TiAg CdRh PdTc RuNb MoY ZrAu HgIr PtRe OsTa WLa Hf
MtBh HsDb SgRf
Dy HoGd TbSm EuNd PmCe Pr Yb LuEr Tm
Cf EsCm BkPu AmU NpTh Pa No LrFm Md
Li BePřirozené radioaktivní prvky ( )
Radionuclide suitable for application in nuclear medicine
99mTcTechnécium - 140 keV
6,0 h
18FFluór+
110 min
111InIndium
- 171, 245 keV2,8 d
67GaGálium
- 93, 184 keV3,26 d
201TlTálium
- 167, 135 keV3,04 d
DiagnostikaTerapie
Pozitronovézářiče
Diagnostic radiopharmaceuticals for SPET
99mTc dominant radionuclide in the NMRadiofarmaceuticals precurzor
source is radionuclide generator
99Mo (-,T1/2=66,2 h) / 99mTc (IT,T1/2=6,02 h)
Other radionuclides for labeling radiopharmaceuticals
201 Tl (EC, T1/2= 72 h) , 67 Ga (EC, T1/2 =77,9 h),111 In (EC, T1/2 =2,8 d), 123 I (EC, T1/2 = 13,2 h),
125 I (EC, T1/2 =60,1 d),
81Rb (EC, +, T1/2 = 4,57h, /81mKr(IT, T1/2 = 13 s)
Radionuclide generator99Mo (-,T1/2=66,2 h) / 99mTc (IT,T1/2=6,02 hod)
99Mo
99Ru
99mTc T1/2 = 6,02 hodin
T1/2 = 66,2 hodin
= 140 keV
-
14%
-
86%
99Tc T1/2 = 2.1 x 105 let
-
100%
99mTc-HMPAO
99mTc-ECD
Na99mTcO4
99mTc-HIDA
99mTc-SESTAMIBI
99mTc-L,L-EC
99mTc-PEG liposomy
99mTc-Q12
99mTc-SCN
99mTc-IODIDA
99mTc-MAG3
99mTc-(V)-DMSA
99mTc-(III)-DMSA
99mTc-anti-SSEA-1
99mTc-GH
99mTc-MIBI99mTc-DTPA
99mTc-MDP
99mTc-EHDP
99mTc-citrát
99mTc-DPD
99mTc-PYP
99mTc-DMPE
99mTc-EDTMP
Další…
Diagnostic radiopharmaceuticals
for PETEmission + , anihililation gama kvant 511 keV
Cyclotron radionuclide preparation Cyclotron radionuclide preparation
Biogen nuclide, short T/2, Biogen nuclide, short T/2,
preparation( syntetisationpreparation( syntetisation automat), aseptic preparation , automat), aseptic preparation ,
generator nuclidegenerator nuclide
124124I, I, 86 86 YY
intravenose aplicationintravenose aplication
Positron (+) radiation - annihilation
p n + + +
18F
= 511 keV
= 511 keV
OF 188
189
1. a proton inside the 18F nucleus turns to a neutron while a positron (+) and a neutrino are emitted
2. positron gradually loses kinetic energy during interaction with surrounding atoms
3. positron combines with an surrounding electron
4. positron and electron are being converted to the gamma photons which are emitted at 180° to each other, each with energy 511 keV - annihilation
Application of Positron Emission Tomography
Cerebral oxygen extraction and metabolism: [15O]-O2
Cerebral blood volume: [15O]-CO2
Myocardial blood volume: [15O]-CO2,
Cerebral blood flow: [15O]-H2O, [11C]-n-bulanol
Myocardial blood flow: [15O]-H2O, [ 13N]-ammonia , [82Rb]-Rb+
Cerebral glucose metabolism: [ 11C]-glucose, [18F]-FDG
Myocardical metabolism: [ 11C]-palmitate, [ 11C]-acetate
Myocardial glucose metabolism: [18F]-FDG
Tumour glucose metabolism: [18F]-FDG
Dopamine receptor binding: [18F]-spiperone, [ 11C]-N-methylspiperone Estrogen receptor binding: [18F]-16-fluoro-17-estradiol
Plasma volume: [68Ga]-citrate
18F - Physical properties
8O
9F
+ 96.73%EC 3.27%
T1/2 = 109.8 minutes
E+max = 635 keV
E = 511 keV
Methods of preparation:
18O ( p , n ) 18F 16O ( , 2n ) 18F
16O ( 3He , n ) 18Ne 18F 20Ne ( d , ) 18F
16O ( 3He , p ) 18F 20Ne ( 3He , p ) 18F
16O ( , pn ) 18F 20Ne ( 3He , n ) 18Ne 18F
18
18
The metabolic „fate“ of glucose (GLU) and FDG
The metabolic pathways of FDG are blocked after formation of FDG-6-phosphate (FDG-6-Phos) FDG remains in tissue.
FDG
Glucose is used as a source of energy
Alu
min
a c
ou
mn
C-1
8 c
olu
mn
Ta
rge
t w
ate
r re
cov
ery
co
lum
n
Ma
nn
ose
tri
fla
te
Labelling vesselC-18 column for hydrolysis
18F-FDG synthesis assembly
Radiochemical purity - HPLC method
• The area of each peak is proporcional to radioactivity of 18F in selected form
• radiochemical purity is given by
Ai = area of 18F-FDG peak
i=total peak area
[%]100 Ai
Ai
Radiodetection using a NaI (Tl) scintilation detector
[18F]NaF injekce- picture of rabbit
Laboratory rabits, M, m = 3,1 kg, activity 130 MBq i.v., 60 min before investigation
ECAT EXACT2D, TAC = 68Ge/GaEm = 5,6‘Tx = 2,4‘
Biograph duo LSO3D, TAC = CTEm = 3,0‘Tx = ?‘‘
UT ~ UT ~
Nucleoside overview1. Contended in the deoxyribonucleid acid
(DNA)
2. Contended in the ribonucleid acid (RNA)
3´-FLT and biosynteze DNA
thymidin 3´-[18F]FLT
• vazebná skupina –OH nahrazena –F• řetězec DNA ukončen – nelze
fosfodiesterovou vazbou navázat další nukleosid
A,T,G,C – dusíkaté báze, P – H3PO4, - deoxyribóza
Therapeutic radionuclideRadionuclide for teletherapy
60Co , 137Cs Radionuklidy for brachytherapy
192 Ir, 145 Sm ,103Pd , 125I Palliative aplication
[89Sr]SrCl2, ,,[153Sm]SmEDTMP (etylendiaminN,N,Nˇ,Nˇ,-
tetrakismethylenfosfonová kyselina)
[186 Re] ReHEDP (hydroxyethylendifosfonová kyselina)
Radiation synovectomycompounds 166Ho, 186Re, 90Y
Therapeutic radiofarmaka Compounds 131I, 32 P, 188Re, 90Y, 166Ho , radiolanthanoides
Immunotherapeutics- requested no added carry (carry free radionuclide 90Y, 188Re
Therapeutic and maximum range of radionuclides in
tissue
Radionuklid Terapeut.dosah (mm) Maximální dosah (mm)32P 2.2 7.990Y 2.8 10.8
153Sm 0.7 3.1165Dy 1.3 5.6166Ho 2.1 8.7186Re 1.0 4.5188Re 2.1 10.1198Au 0.9 3.9
5. L.S.Johnson, J.C. Yanch, S. Shortkoff, C.L. Barnes, A.I. Spitzer, C.B. Sledge: Eur. J. Nucl. Med. 22, 977(1995).ÚJF AV ČR,Laboratoř PET radiofarmak,1998
Chelation compounds
DTPADiethylentetraaminpentaacetyl
acid
DOTA1,4,7,10 –tetraazacyklododekan-N,N,,N,,,
N,,,, tetraacetyl acid
H4do3a-PBnNH2
10-[4-aminobenzyl(hydroxy)fosfonylmethyl]-
1,4,7,10-tetraazacyklo-1,4,7-triacetyl acid
166Ho - Basic Information
166Ho Physical Properties Overview
- Radiation
• Maximum Energy: 1.85 MeV1.77
MeV Gamma Radiation
• Energy: 81 keV
1379 keV
Half life time: 26.8 hours Daughter isotope:Eu-166 (stable)
• Therapeutic effect: 2.1 mm
• Max. soft tissue penetration: 8.5 mm
Production of 166Ho
Nuclear reactor: 165Ho (n, ) 166Ho activation
Neutron Flux: 1013 - 1014 neutr.cm-2.s-1
• Gamma Camera detection of 166Ho after injection
166Ho-Macroaggregates
Rheumatoid Arthritis Treatment
The Principle of Therapy
Inflamed synovial membrane destruction
The Method of Treatment
Radiation synovectomy
Suspension of 166Ho-Macroaggregates particles injection into the diseased joint
Particles are trapped by the inflamed synovial membrane
Destruction of the membrane through radiation
Advantages of the Therapy
Does not require the hospital stay and long rehabilitation period
Minimise of the risks associated with surgery
Disadvantages non-biodegradable particles
CHITOSAN CHARACTERISATION AND MEDICAL APPLICATIONS [1-3]
organic matrix in skeletons of crabs, biodegradable, biocompatible, non-toxic pharmaceutical carriers,
hemostatics and blood anticoagulants, aggregation of leukemia cells,
enzyme immobilization, hypocholesterolemic activity -inhibition of micille formation,
adsorption of cholesterol, fatty acids and monoglycerides, metal ion chelation (amino groups of chitosan),
gel-forming in neutral conditions, soluble and viscous in acidic conditions.
1. Muzzarelli R.A.: Chitin, Pergamon Press, New York,19782. The Polysaccharides v.3 Edited by G.O.Aspinall, Academic Press, Inc. 19853. Šístková N.V., Franta P., Melichar F. : Report NPI, NRI 1998
top related