Radiopharmaceuticals františek Melichar

  RADIOPHARMACEUTICALS

• František Melichar

• UK 3. LF Praha

Radiopharmaceuticals Scope of Presentation

• Basic information

• Diagnostic radiopharmaceuticals

• SPECT,
• PET

• Therapeutic radiopharmaceuticals

• palliative radiopharmaceuitcals
• Immunotherapeutic radiopharmaceuticals
• radiation synovectomy

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

Radiopharmaceuticals

• Difference

• between

• radiochemicals and radiopharmaceuticals

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 accelerators

• 68Zn (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 radionuclides

• 99Mo/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

• Type of radiopharmaceutical for diagnostic and therapy

• Parenteral pharmaceuticals (solutions or colloid suspenses),

• peroral pharmaceuticals

• inhalation pharmaceuticals

• topic pharmaceuticals

Radionuclide suitable for application in nuclear medicine

Diagnostic radiopharmaceuticals for SPET

• 99mTc dominant radionuclide in the NM

• Radiofarmaceuticals 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 generator 99Mo (-,T1/2=66,2 h) / 99mTc (IT,T1/2=6,02 hod)

Sorption generator

Diagnostic radiopharmaceuticals for PET

• Emission + , anihililation gama kvant 511 keV

Positron (+) radiation - annihilation

Application of Positron Emission Tomography

18F - Physical properties

• 8O

Cyclotron production of 18F

Cyclotron U-120M

Target equipment

The metabolic „fate“ of glucose (GLU) and FDG

Oncology

Process of 2-[18 F]FDG syntesis

18F-FDG synthesis assembly

Radiochemical purity - HPLC method

[18F]NaF, injection – syntetisation modul

[18F]NaF injekce- picture of rabbit

3´-FLT and biosynteze DNA

Therapeutic radionuclide

• Radionuclide 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 synovectomy compounds 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

Chelation compounds

166Ho - Basic Information

• 166Ho Physical Properties Overview

•  - Radiation
• Maximum Energy: 1.85 MeV 1.77 MeV
• Gamma Radiation
• Energy: 81 keV 1379 keV
• Half life time: 26.8 hours
• Daughter isotope: Eu-166 (stable)

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

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.