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Molecular Targeting With Radioisotopes-Application of Laser-Driven Isotopic Production PowerPoint Presentation

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Description : Check out this medical PowerPoint presentation titled "Molecular targeting with radioisotopes: application of laser-driven isotopic production” by Dana Niculae, PhD.

This medical PowerPoint presentation is about molecular targeting with radioisotopes, is a technique that is used in nuclear medicine to diagnose and treat various diseases, such as cancer. This technique involves the use of radioactive isotopes that are specifically targeted to the site of the disease, such as cancer cells. Once the radioactive isotope is at the site of the disease, it emits radiation that can destroy or shrink the cancer cells.

One method of producing these radioactive isotopes is through laser-driven isotopic production. This process involves using high-intensity lasers to produce short-lived isotopes that can be used for molecular targeting.

The laser-driven isotopic production process starts with a high-intensity laser that is focused on a target material, such as a thin foil. The laser heats the target material to an extremely high temperature, causing it to ionize and form a plasma. As the plasma cools, short-lived isotopes are produced through nuclear reactions.

These short-lived isotopes can then be extracted from the plasma and used for molecular targeting. One advantage of this method is that it can produce isotopes with a very short half-life, which means that they decay quickly and produce less radiation in the body. This reduces the risk of damage to healthy tissues surrounding the site of the disease.

In summary, laser-driven isotopic production is a promising technique for producing short-lived isotopes that can be used for molecular targeting in nuclear medicine. With further research and development, this technique may become a valuable tool in the diagnosis and treatment of various diseases.

Tags : Molecular targeting with radioisotopes, laser-driven isotopic production,radioactive isotopes, Nuclear Medicine, Nuclear Medicine PowerPoint presentation

Published on : Jun 20, 2023 | Views : 1291 | Downloads : 0

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Slide 1-

Molecular targeting with radioisotopes: application of laser-driven isotopic production Dana Niculae, PhD Horia Hulubei National Institute for Physics and Nuclear Engineering, IFIN-HH, Romania
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overview (Some) statistics about use of radioisotopes in nuclear medicine What are the needs of modern medicine? Examples of the use of medical radioisotopes Emerging radioisotopes and production routes Estimates of the production of radioisotopes at ELI-NP D. Niculae, seminar at UCIrvine October 2016 2
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Statistics - radioisotopes in nuclear medicine Over 10,000 hospitals worldwide use radioisotopes in medicine, and about 90% of the procedures are for diagnosis. The most common radioisotope used in diagnosis is Tc-99m, accounting for about 80% of all nuclear medicine procedures Over 40 million nuclear medicine procedures are performed each year, and demand for radioisotopes is increasing at up to 5% annually. In developed countries (26% of world population) the frequency of diagnostic nuclear medicine is 1.9% per year. In the USA there are over 20 million nuclear medicine procedures per year among 311 million people, and in Europe about 10 million among 500 million people. The global radioisotope market was valued at $4.8 billion in 2012, with medical radioisotopes accounting for about 80% of this, and is poised to reach about $8 billion by 2017. North America is the dominant market for diagnostic radioisotopes with close to half of the market share, while Europe accounts for about 20%. (World Nuclear Association, http://www.world-nuclear.org updated September 2016) The number of requests by both patients and doctors for state-of-the-art nuclear medical imaging procedures has increased seven fold in the last 25 years Computed X-ray tomography (CT) scans and nuclear medicine contribute 36% of the total radiation exposure and 75% of the medical exposure to the US population, average total yearly radiation exposure had increased from 3.6 mSv to 6.2 mSv per year since the early 1980s due to medical-related procedures. (Report of the National Council on Radiation Protection and Measurements, 2009) D. Niculae, seminar at UCIrvine October 2016 3
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Statistics - radioisotopes in nuclear medicine Over 10,000 hospitals worldwide use radioisotopes in medicine, and about 90% of the procedures are for diagnosis. The most common radioisotope used in diagnosis is Tc-99m, accounting for about 80% of all nuclear medicine procedures Over 40 million nuclear medicine procedures are performed each year, and demand for radioisotopes is increasing at up to 5% annually. In developed countries (26% of world population) the frequency of diagnostic nuclear medicine is 1.9% per year. In the USA there are over 20 million nuclear medicine procedures per year among 311 million people, and in Europe about 10 million among 500 million people. The global radioisotope market was valued at $4.8 billion in 2012, with medical radioisotopes accounting for about 80% of this, and is poised to reach about $8 billion by 2017. North America is the dominant market for diagnostic radioisotopes with close to half of the market share, while Europe accounts for about 20%. (World Nuclear Association, http://www.world-nuclear.org updated September 2016) D. Niculae, seminar at UCIrvine October 2016 4
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Estimates of worldwide use (per 100,000 people) of nuclear cardiology procedures. Dominique Delbeke, and George M. Segall J Nucl Med 2011;52:24S-28S (c) Copyright 2014 SNMMI; all rights reserved
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Statistics - radioisotopes in nuclear medicine Breakdown of diagnostic imaging procedures Source: Natural Resources Canada, 2009. Composition of Nuclear Medical procedures where Tc-99m is predominant Source: http://www.arpansa.gov.au D. Niculae, seminar at UCIrvine October 2016 6
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Personalized Medicine Predictability Diagnosis Information Treatment What is the major challenge in medical research? What are the needs of modern medicine ? D. Niculae, seminar at UCIrvine October 2016 7
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What are the needs of modern nuclear medicine ? Imaging Early diagnosis Therapy follow-up High quality images Low radiation dose Unlike other tests/procedures, nuclear medicine provides information about the function of virtually every major organ system within the body. Advances in technology, including hybrid imaging, Introduction of new radiopharmaceuticals for diagnosis/therapy Development of molecular imaging based on the tracer principle D. Niculae, seminar at UCIrvine October 2016 8
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Targeted therapy Targeting high specificity Efficacy high selectivity Therapy follow-up High amount of energy imparted to the target tissue (to destroy cancer cells) relative to critical normal organs and tissues (to prevent radiation damage and side-effects) What are the needs of modern nuclear medicine ? D. Niculae, seminar at UCIrvine October 2016 9
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Emerging radioisotopes and (alternative) production routes Therapeutical radioisotopes Advancing Nuclear Medicine Through Innovation Natl. Academies Press Due to the crossfire effect more complex (heterogeneous) tumors may benefit from targeted radionuclide therapy The bystander effect in should be investigated as it contribute to the total therapeutic effect Induced radioresistance and radiosensitivity Penetration of alpha and beta particles in tissue D. Niculae, seminar at UCIrvine October 2016 10
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Targeting moieties on cell surface/inside cell D. Niculae, seminar at UCIrvine October 2016 11
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MOLECULAR IMAGING / SYSTEMIC RADIOTHERAPY RADIOPHARMACEUTICALS D. Niculae, seminar at UCIrvine October 2016 12
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SCHEMATIC REPRESENTATION OF A DRUG FOR IMAGING AND TARGETED THERAPY Molecular Address Antibodies, their fragments and modifications Regulatory peptides and analogs thereof Amino Acids Target Antigens (CD20, HER2) GPCRs Transporters Reporting Unit 99mTc, 111In, 67Ga 64Cu, 68Ga Gd3+ Cytotoxic Unit 90Y, 177Lu, 213Bi 105Rh, 67Cu, 186,188Re Courtesy prof H. Maecke, Basel D. Niculae, seminar at UCIrvine October 2016 13
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Coronary Artery DiseaseMeasure Effectiveness of Bypass Surgery Measure Effectiveness of Therapy for Heart FailureDetect Heart Transplant Rejection Select Patients for Bypass or Angioplasty Identify Surgical Patients at High Risk for Heart Attacks Identify Right Heart Failure Measure Chemotherapy Cardiac Toxicity Evaluate Valvular Heart DiseaseIdentify Shunts and Quantify Them Diagnose and Localize Acute Heart Attacks before Enzyme Changes Pulmonary Applications: Diagnose Pulmonary EmboliDetect Pulmonary Complications of AIDS Quantify Lung Ventilation and Perfusion Detect Lung Transplant RejectionDetect Inhalation Injury in Burn Patients Examples - use of medical radioisotopes Renal Applications: Detect Urinary Tract Obstruction Diagnose Renovascular Hypertension Measure Differential Renal Function Detect Renal Transplant Rejection Detect Pyelonephritis Detect Renal Scars Neurologic Applications: StrokeAlzheimer’s DiseaseDemonstrate Changes in AIDS Dementia Evaluate Patients for Carotid Surgery Localize Seizure FociEvaluate Post Concussion Syndrome Diagnose Multi-Infarct Dementia Oncology Applications: Tumor LocalizationTumor StagingIdentify Metastatic SitesJudge Response to TherapyRelieve Bone Pain Caused by Cancer Ortophedic Applications: Identify Occult Bone Trauma (Sports Injuries) Diagnose Osteomyelitis Evaluate Arthritic Changes and Extent Localize Sites for Tumor Biopsy Measure Extent of Certain Tumors Identify Bone Infarcts in Sickle Cell Disease Detect Occult InfectionsDiagnose and Treat Blood Cell Disorders Diagnose and Treat Hyperthyroidism (Graves’ Disease) Detect Acute CholecystitisChronic Biliary Tract DisfunctionDetect Acute Gastrointestinal Bleeding Detect Testicular Torsion Cardiac Applications: Other Applications:
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Cancer therapy demonstrated with 90Y–ibritumomab tiuxetan (Zevalin)Peter Conti, University of Southern California – NCI Report 2008 October 2016 Nuclear Photonics 15 / 23 D. Niculae, seminar at UCIrvine October 2016 15
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F-18-FET Brain tumor Neuroinflammation D. Niculae, seminar at UCIrvine October 2016 16
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[18F]CHOLINE [18F]Fluoromethylcholine [18F]Fluoroethylcholine D. Niculae, seminar at UCIrvine October 2016 17
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[18F]CHOLINE Prostate cancer D. Niculae, seminar at UCIrvine October 2016 18
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[11C]Tracers Synthesis of cell membrane phospholipids Protein synthesis Fatty-acid metabolism [11C]Choline D. Niculae, seminar at UCIrvine October 2016 19
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Astrocytoma (no response) (courtesy by PET Centre St. Orsola Hospital, Bologna) After therapy Before therapy [11C]Methionine D. Niculae, seminar at UCIrvine October 2016 20
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Emerging radioisotopes and (alternative) production routes All medical radioisotopes now produced in reactors can be produced alternatively or can be replaced by isotopes which can be produced other than in a nuclear reactor Particle Accelerators Linear Ge-68/Ga-68, and Sr-82/Rb-82, Zn-65, Mg-28, Fe-52, Rb-83 (200 MeV proton beam, 150 uA) Cyclotrons (10-100 MeV, up to 2 mA) F-18, Sr-82, Cu-64,O-15, C-11, Br-77, I-124, Y-86, Ga-66/68, Cu-60/61, Zr-89, Tc-99m New routes Compact systems (Bench-scale electronic devices for achieving various high-energy nuclear reactions): proton accelerator: production of F-18, In-111, I-123, C-11, N-13, O-15 alpha linac: Sn-117m, Ac-225, As-73, Fe-55, At-211, Cd-109, Y-88, Se-75, Po-210 neutron sources Electron-beam accelerator Bremsstrahlung 10-25 MeV electrons proposed for isotope production through: Photo-fission of heavy elements (γ ,n) reactions Photo-neutron activation and (n,2n) reactions D. Niculae, seminar at UCIrvine October 2016 21
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Emerging radioisotopes and (alternative) production routes Emerging medical radioisotopes: β-emitters and theragnostic agents – in preclinical and clinical research: Lu-177, Ho-166, Re-186/188, Cu-67, Pm-149, Au-199, Y-90 D. Niculae, seminar at UCIrvine October 2016 22
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Emerging radioisotopes and (alternative) production routes Emerging medical radioisotopes: α-emitters and Auger-electrons emitters D. Niculae, seminar at UCIrvine October 2016 23
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ELI–NP GBS Layout e– RF LINAC Low Energy 300 MeV Interaction Laser Low Energy Photo–gun Laser Photo–gun e– source Low Energy Gamma Beam < 3.5 MeV D. Niculae, seminar at UCIrvine October 2016 24
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ELI–NP GBS Layout e– RF LINAC Low Energy 300 MeV Interaction Laser High Energy Interaction Laser Low Energy Photo–gun Laser e– RF LINAC High Energy 720 MeV Photo–gun e– source High Energy Gamma Beam < 19.5 MeV
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ELI–NP GBS Parameters D. Niculae, seminar at UCIrvine October 2016 26
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Potential radioisotopes produced in (γ,n), (γ,p) or (γ,2n) reactions D. Habs · U. Köster, Appl Phys B (2011) 103: 501–519
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Potential radioisotopes produced in (γ,n), (γ,p) or (γ,2n) reactions -cont D. Habs · U. Köster, Appl Phys B (2011) 103: 501–519
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Potential radioisotopes produced in (γ,n), (γ,p) or (γ,2n) reactions -cont D. Habs · U. Köster, Appl Phys B (2011) 103: 501–519 For β and ε decay mode, the emission energy is the mean energy. *Estimated cross sections are marked in italics. D. Niculae, seminar at UCIrvine October 2016 29
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170Er 169Er Stable T1= 9.4 d 169Tm β-, 100 keV Stable (γ,n) Abundance:14.9% 166Er 165Er Stable T1=10.4 h 165Ho ε, 5 and 38.4 keV Stable (γ,n) Abundance: 33.5% γ, 0.05 MeV 65Cu 64Cu Stable T1= 12.7 h 64Ni Stable Abundance:30.85% β-, 191 keV (γ,n) ε , 278 keV 64Zn T2>7.e20 y γ , 0.511 Due to the low 168Er(nth, γ) cross section, it cannot be produced with higher specific activity[1] by neutron capture. Today, 64Cu is mainly produced with small cyclotrons by the 64Ni(p,n) reactions, which require the rare and expense 64Ni targets and saves the chemical separation step. D. Niculae, seminar at UCIrvine October 2016 30
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[1] J.C. Reubi, H.R. Mäcke, E.P. Krenning, J. Nucl. Med. 46, 67S (2005) [2] M.J. Rivard, L.M. Bobek, R.A. Butler, M.A. Garland, D.J. Hill, J.K. Krieger, J.B. Muckerheide, B.D. Patton, E.B. Silberstein, Appl. Radiat. Isotopes 63, 157 (2005) 48Ti 47Sc Stable T1= 3.35 d 47Ti β-, 162 keV Stable (γ,p) Abundance: 73.7% γ, 159 keV 187Re 186Re Stable T1=3.7 d 186Os β-, 347 keV (γ,n) Abundance: 62.6% γ, 137 keV T2>2.e15 y The 47Sc could be chemically separated from the irradiated Ca or Ti element. The Sc/Ti separation schemes were established. The alternative production via 46Ca(n,γ)47Ca→47Sc is uneconomic due to the extremely low natural abundance of 46Ca, 0.004%. 48Ca 47Ca T>5.8e22 y T1= 4.54 d 47Sc β-, 400 keV T1= 3.35 d (γ,n) Abundance: 0.2% γ, 1.3 MeV D. Niculae, seminar at UCIrvine October 2016 31
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46Ti 44Ti Stable T1= 59.1 y 44Sc ε (γ,2n) Abundance: 8.25% γ, 0.07 MeV 44Ca ε, 632 keV γ, 511 keV 1157 keV T2= 3.97 h Stable 44Sc has very favorable properties, but not yet used in clinical routine, since the generator isotopes 44Ti is difficult to produce and therefore prohibitively expensive. Exposing enriched 46Ti to an intense γ-beam allows producing 44Ti by (γ,2n) reactions. D. Niculae, seminar at UCIrvine October 2016 32
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Alike 47Sc, 67Cu has a sufficiently long half-life for accumulation in the tumor cells when bound to antibodies and its 185 keV gamma-ray allows imaging with SPECT or gamma cameras. The usual production routes 68Zn(p,2p), 70Zn(p,α), or 64Ni(α,p), are all characterized by low yields. The former requires energetic protons (>30 MeV from larger cyclotrons) and the latter two methods use expensive enriched targets with low natural abundances, of the order of 0.5%. Production via 68Zn(γ,p) reactions, more abundant and hence cheaper 68Zn targets could be used. An established Cu/Zn separation schemes. 68Zn 67Cu Stable T1= 2.6 D β-, 141 keV (γ,p) 67Zn Stable γ , 185 keV Abundance: 18.5% 104Pd 103Pd Stable T1=17 d 103Rh CE, 36 keV (γ,n) Abundance: 11.14% γ, 20 keV Stable D. Niculae, seminar at UCIrvine October 2016 33
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The noble gas 220Rn isotope can be extracted easily. The α emitter 212Bi and its mother isotopes 212Pb are also considered for targeted alpha therapy, e.g., for malignant melanoma metastases. A competing reaction 226Ra(γ,n)225Ra could be used for 225Ac/213Bi generator also for targeted alpha therapy. 226Ra (γ,2n) 224Ra α 220Rn T0= 1600 y T1= 3.66 D T2= 55.6 s 216Po T3= 0.145 s α En=6.3 MeV 212Pb T3= 10.64 h α En=6.8 MeV 212Bi T1= 60.6 min 100 keV β- 208Tl T0= 3 min α, En=6.05 MeV (36%) 212Po T0= 0.3 μs β-, En=0.77 MeV (64%) 208Pb β-, En=0.56 MeV α, En=8.8 MeV Stable 5.7 MeV D. Niculae, seminar at UCIrvine October 2016 34
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Conclusions Are there “ideal” radioisotopes for imaging/therapy (physical, chemical and biological properties)? What emerging radioisotopes can improve in any of these views? What are the limitations for both “traditional” and “emerging” radioisotopes in term of production routes, availability, processing, to access into clinical practice? Can radioisotopes address functionality / early diagnosis / personalized medicine ? October 2016 Nuclear Photonics 35 / 26 D. Niculae, seminar at UCIrvine October 2016 35
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October 2016 Nuclear Photonics 36 / 26 Photonuclear reactions with γ beams allow to produce certain radioisotopes, 47Sc, 44Ti, 67Cu/(64Cu), 103Pd, 117mSn, 169Er, 195mPt , 225Ac, 99Mo (99mTc), 111In with higher specific activity and/or more economically than with classical methods. New clinical applications of radioisotopes: Monitoring of the response to therapy (in real-time) Theragnostic agents 64/67Cu used as reporting and therapeutical Increased availability of very promising radioisotopes innovative isotopes like 47Sc, 67Cu and 225Ac could be produced for the first time in sufficient quantities for large-scale application in targeted radionuclide therapy. Development of alternative methods for producing well established radioisotopes in clinical practice Conclusions D. Niculae, seminar at UCIrvine October 2016 36
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Thank you for attention!