Positron Emission Tomography Basics: Radiochemistry. Scott Mason, Ph.D. Radiochemist PET Facility
What is PET? Positron Emission Tomography In-Vivo Imaging and Quantification of rgan/tissue Function Uses Positron-Emitting Radiolabeled Tracers
What is PET? Positron Emission Tomography In-Vivo Imaging and Quantification of rgan/tissue Function Uses Positron-Emitting Radiolabeled Tracers
PET Imaging 1. Cyclotron 2. Radionuclide 3. Radiosynthesis 4. PET Imaging 5. Image Reconstruction 6. Data Analysis
PET Imaging 1. Cyclotron 2. Radionuclide 3. Radiosynthesis 4. PET Imaging 5. Image Reconstruction 6. Data Analysis
Cyclotron
Positron Emitting Radionuclides Atoms that can be included in amino acids, carbohydrates, steroids, water, other small molecules, etc. (F is isostere for H) Short half-life: maximizes SR to subject radiation dose, but also means the isotope must be produced locally ( 18 F can be shipped) Half-life (min)" 18 F 109! 11 C 20! 13 10! 15!2!
Radionuclide Production Cyclotron! Stable uclide! 11 MeV protons! 18! Unstable Radionuclide! n! 18 F!
Radionuclide Production 15 2 p,n 15 2 H 2 16 p,α 13 H3 14 2 + 2 p,α 11 C2 H 2 18 p,n H 18 F
Potential C-11 Chemistry 11 CH 3 Tf 11 CH 3 Li 11 CH 3 2 11 CH 3 I 11 CH 3 H H 11 CH 11 C 2 (CH 3 ) 2 11 C R 11 C 2 MgBr R 11 CH 2 H R 11 C 2 H R 11 CH 2 I R 11 CH R 11 CCl R 11 CH 2 R 11 CHR R 11 CR 2
C-11 Carboxylation Chemistry 11 CH 3 Tf 11 CH 3 Li 11 CH 3 2 11 CH 3 I 11 CH 3 H H 11 CH 11 C 2 (CH 3 ) 2 11 C R 11 C 2 MgBr R 11 CH 2 H R 11 C 2 H R 11 CH 2 I R 11 CH R 11 CCl R 11 CH 2 R 11 CHR R 11 CR 2
[C-11]WAY100635 * Me * Two potential labeling sites
[C-11]carbonyl WAY 100635 MgCl [C-11]C 2 * - * Cl + Me H Me * [C-11]carbonyl WAY100635
C-11 Methylation 11 CH 3 Tf 11 CH 3 Li 11 CH 3 2 11 CH 3 I 11 CH 3 H H 11 CH 11 C 2 (CH 3 ) 2 11 C R 11 C 2 MgBr R 11 CH 2 H R 11 C 2 H R 11 CH 2 I R 11 CH R 11 CCl R 11 CH 2 R 11 CHR R 11 CR 2
[C-11]MeI System
[C-11]MeI System [ 11 C]Methyl Iodide System
[C-11]β-CFT chemistry H 3 11 C H CCH 3 100 µl acetone [C-11]CH 3 Tf CCH 3 F 2 min @ 60 o C HPLC purification F
[C-11]β-CFT micropet Imaging of Simian Unilateral MPTP Lesion Model of Parkinson s Disease Lesioned Striatum MPTP associated toxicity resulted in ~90% loss of DAT sites in left striatum as determined by PET Intact Striatum
Dopamine D2/D3 Imaging: [C-11]FLB457 H H [ 11 C]CH 3 Tf ah H 11 CH 3 Br Me Acetone Br Me
Dopamine D2/D3 Imaging: [C-11]FLB457 Specific Activity Concerns Ratio of radioactivity to cold mass Expressed as Ci/mmole Theoretical 9.4 x 10 6 Routinely achieved 2 x 10 3 Minimize cold mass associated with radioactivity administration (0.6 µg) Atmospheric C 2 acts to decrease specific activity
[C-11]Pittsburgh Compound B [C-11]PIB H S H 2 [ 11 C]CH 3 Tf Methyl Ethyl Ketone H S 11 CH 3 H 6-H-BTA-0 [ 11 C]6-H-BTA-1
[C-11]PIB Images Examples of Pittsburgh Compound-B (PIB) Logan DVR images for a control, a control-like mild cognitive impairment (MCI-2), an AD-like MCI (MCI-4), and the AD (AD-1) subject with highest PIB retention.
F-18 Fluoride Alkyl nucleophilic substitution (S2) Aromatic nucleophilic substitution (S2Ar) Issues Cation exchange and relatively anhydrous conditions
[F-18]FDG chemistry Ac H Ac Tf Ac 1. K[ 18 F], K222 2. HCl H H Ac H 18 F
[F-18]FDG chemistry
[F-18]FLT chemistry DMTr 1. K[ 18 F], K222, DMS 2. HCl H H 18 F
[F-18]FLT uptake in mice bearing xenografted SCCH tumors brain tumors
Metabolite Contribution H S [F-18]Altanserin 18 F H S H H [F-18]Altanserinol 18 F H 18 F [F-18]4-(4-Fluorobenzoyl)piperidine
Radiosynthesis of F-18]Altanserinol H S 2 H S K 18 F DMS hv 18 F EtH abh 4 H S H H 18 F
3 -[F-18]F-6-H-BTA-1 Radiochemistry H 36.54% S 18 F 20.92% HCH 3 [F-18]3'F-PiB Pr 2 2 S Pr 1 12.03% 4.00% CH 3 Precursors
3 -[F-18]F-6-H-BTA-1 Semi-Preparative HPLC 36.54% 20.92% 12.03% 4.00% Prodigy DS-Prep 10 x 250 mm, 3/1/6 MeC/ MeH/ TEA Buffer, 1 ml/min 0-5min, 5 ml/min 5-10 min, then 8mL/min
3 -[F-18]F-6-H-BTA-1 Final Product QC 36.54% 20.92% 12.03% 4.00% Prodigy DS-3 5µ 4.6 x 250 mm, 40% MeC / 60% TEA Buffer, 2.0 ml/min
The Regional Distribution of [18F]3 F-PiB in AD Brain is Very Similar to that of [11C]PiB
Radiopharmacy Quality Control Visual ph T 1/2 determination Radiochemical Identity Radiochemical Purity Chemical Purity (Specific Activity) Residual Volatile rganic Solvent Endotoxin Testing Sterility
Acknowledgments Chester A. Mathis, Ph.D. - Director Chemists Scott Mason Steve Kendro icole DeBlasio April Radelet Guo-feng Huang Physicists Julie Price Brian Lopresti Chip Laymon Eoin Carney Technologists James Ruszkiewicz Denise Ratica Collaborators Raj arendran Clayton Wiley Bill Klunk Jerry Schatten Jennifer Grandis Funding: IA, IMH, CI, CRR, UPMC