Standardization of nuclear data for the production of medical radionuclides

1. Standardization of nuclear data for the production of medical radionuclides M. Hussain1,2,3 Department of Physics Govt. College University, Lahore, Pakistan1 LASA, Lab, Milano, INFN, Italy2 Department of Physics, University of Milan, Italy3

2. Layout • Introduction • Nuclear Medical Centers in Pakistan • Nuclear Data Sources • Standardization of Nuclear Data • Nuclear Model Calculations and Evaluation Methodology • An Example of a Medically Important Radionuclide, 86Y • Future Prospects • Concluding Remarks

3. Radionuclides in Medicine The use of radioisotopes is a well established branch of medicine, both for diagnosis and treatment of disease. • Diagnostic applications • Therapeutic applications • Theranostic applications Objectives: Imaging: minimum dose (γ or β+ emitters) Therapy: suitable localised dose (βˉ , α-particle, Auger Electrons)

4. Imaging techniques in diagnostic nuclear medicine SPECT S……….. Single P………… Photon E…………. Emission C………… Computed T…………. Tomography SPECT scans use γ emitting radioisotopes. Widely available: Lower cost Attenuation correction: Less Accurate Spatial resolution: 10-15 mm Protocol: Several hours Radiation: Greater than 10 mSv Images: Qualitative Longer lived radionuclides: e.g. 99mTc (T1/2= 6 h), 123I (T1/2=13.2h) and 201Tl(T1/2= 3.2d) PET P……….. Positron E…………. Emission T…………. Tomography PET scans use positron emitting radioisotopes. Accurate attenuation correction Spatial resolution: 3-6 mm Protocol: Less than 1 hour Radiation: Less than 10 mSv Images: Quantitative Short lived radionuclides: e.g. 11C (T1/2= 20.4 min), 13N (T1/2=10.0 min ), 15O (T1/2= 2.0min), 18F (T1/2= 110 min)

5. Internal Radionuclide Therapy • Brachytherapy (insertion of sealed sources near the tumour) Examples:192Ir as wire,103Pd and 125I as seeds • Administration in cavities (for pain palliation) Examples:32P colloid for arthritis 90Y, 186Re and 188Re complexes for joint inflammation • Metabolic therapy (incorporation of radionuclide via a biochemical path) Examples:131I for thyroid cancer, 89Sr, 186Re and 153Sm are bone seekers • Radioimmunotherapy (administration of a radionuclide chemically conjugated to antibodies) Examples: low-energy high-LET value radionuclides Internal radionuclide therapy is a fast developing field

6. Radionuclides Commonly used in Nuclear Medicine For SPECT γ-emitters (100 – 250 keV) 99mTc, 123I, 201Tl (used worldwide) Diagnostic Radionuclides • For PET • + emitters • 11C, 13N, 15O, 18F, • 68Ge (68Ga), 82Sr (82Rb) • (fast developing technology) Therapeutic Radionuclides (in-vivo) • --emitters (32P, 90Y, 131I, 153Sm, 177Lu) • α-emitter (211At) • Auger electron emitters (67Ga, 111In, 125I) • X-ray emitter (103Pd) (increasing significance) Status of nuclear data is good

7. Nuclear Medicine in Pakistan

8. Facilities in the Centers • Following facilities are available at centers: • Strong 60Co sources for radiation therapy • Betatrons to produce hard γ–rays for therapy (at few centers) • Gamma Cameras • SPECT-CT, 99mTc • Internal therapy, 131I, 32P • Following centers have PET-CT • INMOL-Lahore • SKCH-Lahore • Agha Khan Hospital-Karachi

9. Regulation of the nuclear facilities

10. International Co-operation….

11. Jülich Research Centre, Jülich, Germany Nuclear Data Section, NDS-Vienna, Austria ATOMKI,Debrecen, Hungary Berkley-Lab, Berkley, USA LASA, Milano, Italy GCU Lahore, Pakistan Debrecen University, Debrecen, Hungary Skoto State University, Nigeria

12. Nuclear Data Needed ucleawelaeir interactions. Nuclear Structure Data Nuclear Data Nuclear Decay Data Nuclear Reaction Data

13. Nuclear data needs and references for experimental and standardized data Choice of a radionuclide depends on decay data • Suitability for imaging • Suitability for therapy Major references for standardized data • NuDat (except mixed EC and PE) • NNDC • Table of radioactive isotopes • RIPL-3 Optimisation of production procedure depends on reaction cross sections • Maximise product yield • Minimise radioactive impurity level Major reference for experimental data • EXFOR

14. Nuclear data for medical applications- IAEA • Consultants Meeting on Nuclear Data for Medical Radioisotope Production (IAEA, Vienna, April 1981)-Report INDC(NDS)-123. • Consultants Meeting on Data Requirements for Medical Radioisotope Production, (Tokyo, April 1987)-Report INDC(NDS)-195. • Advisory Group Meeting on Intermediate Energy Data for Applications, Working Group on Nuclear Data for Medical Applications. (IAEA, Vienna, October 1990)-Report INDC(NDS)-245. • CRP on “Charged particle cross-section database for medical radioisotope production: diagnostic radioisotopes and monitor reactions”. IAEA-TECDOC-1211 (2001). • CRP on “Nuclear Data for the Production of Therapeutic Radionuclides” IAEA-TRS-473 (2011). • CRP on “Nuclear Data for Charged-particle Monitor Reactions and Medical Isotope Production”. Summary Report- IAEA-INDC (NDS)-630 (2013). (All meetings and CRPS up to 2011 under the Chair of Prof. Qaim)

15. Cont-

16. Evaluation methodology • The evaluation methodology was developed under the auspices of the IAEA. It consists of following steps: • Thorough search of literature and compilation of available experimental data from different sources, with complete details. • Check the reliability of experimental data and reject unreliable data with reasoning. • Check consistency of data reported by different laboratories and analyze the systematic trends in data. • Normalization of data according to the latest agreed standards (monitor reaction, gamma ray intensities and half-life etc.)

17. Cont- • Nuclear model calculation (Code ALICE/TALYS/EMPIRE) while carefully choosing the input parameters. • Comparison of the literature data with calculations performed by nuclear model codes. • Basic consideration: σev (E) = f (E) σmodel (E) • Fitting of ratio data (measured/model calculation) using statistical ways, particularly spline fitting along with the 95% confidence limits and neglecting the data that lie beyond 3σ limit. • Fitting of the remaining data by using a polynomial function and generation of the recommended excitation function that should be used for the production of radionuclide and calculation of yield.

18. Why 86Y Two important new developments in the application of radionuclides have been emerging. 1- A combination of PET and internal radiotherapy (theranostic approach) i.e. combination of Diagnostic and Therapeuticradioisotopes. 2- A combination of PET and magnetic resonance imaging (MRI). The theranostic approach uses a β+ emitting and a therapeutic radionuclide of the same element are simultaneously injected in a patient, as it was originally done using 86Y (T1/2=14.74h) and 90Y (T1/2=2.7d) at Jülich in 1993. 90Y was available through a generator system; 86Y had to be developed. Other potential theranostic pairs are: 44Sc/47Sc, 64Cu/67Cu, 124I/131I, etc.

19. Decay Data of Y-radionuclides

20. Investigated Nuclear Reactions

21. Excitation Function of 86Sr(p,n)86Y Reaction

22. Recommended Cross section Data

23. Major RadionuclidicImpurities • Theory is not very successful in case of isomers. More reliance on experimental data.

24. Calculated Integral Yield of 86Y

25. Recommended Data for the 88Sr(p,3n)86Y Reaction

26. Comparison of production routes of 86Y * Experimentally determined values by Rösch et al. (1993a) under real production conditions.

27. Evaluation completed at the GCU Lahore in collaboration with FZJ and IAEA • β+ emitter • 55Co, • 61Cu, 64Cu, • 66Ga, 68Ga, • 76Br • 86Y, 124I • Therapeutic Radionuclides • 103Pd, • 186Re

28. Future Prospects: Evaluation of Data of Novel Positron Emitters for Medical Applications

29. Evaluation of Data of Novel Therapeutic Radionuclides: 47Ca (T½ = 3.4 d; Eβ- = 610 keV) 67Cu (T½ = 2.6 d; Eβ- = 577 keV) 225Ac (T½ = 10.0 d; Eα = 5830 keV) 131Cs (T½ = 9.7 d; X-rays) 117mSn (T½= 13.6 d; Conversion electrons) 193mPt (T½ = 4.3 d; Auger electrons)

30. Concluding Remarks • Nuclear medicine is getting established worldwide. • Pakistan is raising its capacity to use medical radionuclides. • Nuclear data play a vital role in the process of production and use of radionuclides. • Standardization involves the study of decay data, reaction data, monitor reaction cross sections. • Evaluation of the cross section data is done with the help of nuclear model codes, i.e. ALICE, EMPIRE and TALYS. • Standardization of nuclear data helps to optimize the production conditions of radionuclides for medical applications, e.g. 86Y, 186Re etc.

31. Thank you for your patience

32. Activation formula • λ : Decay constant of radionuclide (S-1) • C : Counts under peak area of desired radionuclide • ε : Efficiency of HPGe detector • Iγ : Intensity of gamma line or branching ratio • tm : Spectrum acquision or measurement time (S) • ti : Itrradiation time (S) • tc : Cooling time (S) • n : Number of particles in target (#/cm2) • φ : Beam flux (S-1)

34. Nuclear Model Calculations • Optical model for the absorption cross sections, as well as for the transmission coefficient calculations; • Direct, pre-equilibrium and compound processes are taken into consideration; • Complete schemes of low-lying nuclear levels and a consistent description of nuclear level densities at higher excitations.