Radiochem non metals Scott.pdf

Non-metal Radionuclides 3. 11C, 13N, 15O, 124I Presentation developed by: Peter J. H. Scott, Ph.D.  1. Carbon-11 2. Nitrogen-13 3. Oxygen-15 4. Iodine-124 5. Summary 1. Carbon-11 Production and Properties Decay Product 11B  Carbon-11...

Non-metal Radionuclides 3. 11C, 13N, 15O, 124I Presentation developed by: Peter J. H. Scott, Ph.D.  1. Carbon-11 2. Nitrogen-13 3. Oxygen-15 4. Iodine-124 5. Summary 1. Carbon-11 Production and Properties Decay Product 11B  Carbon-11 target is filled with 14N2 gas – 14N(p,)11C  -p a rtic le p ro to n N -1 4 C -1 1 Target gas is spiked with 0.5% O2 or H2, generating [11C]CO2 or [11C]CH4, respectively Carbon-11 Radiochemistry  Cyclotron target gas is spiked with 0.5% O2 or H2, generating [11C]CO2 or [11C]CH4, respectively [11C]CO2 or [11C]CH4 are transferred to a synthesis module where they are converted to a different synthon or, in the case of [11C]CO2, also used directly Common carbon-11 synthesis module interface Carbon-11 Synthons  Reactions with [11C]CO2 Typical reactions using [11C]CO2 involve Production of (a) [11C]acetate and (b) [11C]palmitate 11C-Methylation 1: [11C]CH3I and [11C]CH3OTf 11C-Methylation 2: Synthesis of [11C]Pittsburgh Compound B by Methylation Reactions with [11C]HCN Examples of11C-Labeled Radiopharmaceuticals  [11C]Acetate Produced by bubbling [11C]CO2 through MeMgBr; Acetate is metabolized into acetyl-CoA in cells. It then either enters the tricarboxylic acid cycle, producing energy, as happens in the myocardium, or Patient with meningothelial meningioma participate in cell membrane lipid (grade I). (A) MR image (T1-weighted image synthesis, as happens in tumor cells. after gadolinium injection) showing necrotic 11C-acetate PET was originally employed lesion with heterogeneous contrast in cardiology, to study myocardial oxygen enhancement in right parietal region. (B) PET metabolism. More recently it has also image showing high uptake of [11C]acetate been used to in oncology. (SUV, 3.06; T/C ratio, 3.82) (B) Liu et al., J. Nucl. Med. 2010, 51, 883.  [11C]Choline Produced by 11C-methylation of dimethylaminoethanol; 76 y.o. patient. Biochemical relapse 9 yrs after radical Choline is phosphorylated by prostatectomy. PSA 1.43 ng/mL at time of 11C-Cho PET/CT. choline kinases within cells, and integrated into phospholipids. Because tumor cells have a high metabolic rate, choline uptake is high. [11C]Choline is useful for the detection of brain tumors, prostate cancer, lung cancer, and esophageal cancer. [11C]Choline PET of a brain tumor Picchio and Castellucci, Theranostics 2012; Giovacchini, Nuclear Oncology  [11C]Pittsburgh Compound B ([11C]PiB) Produced by 11C-methylation as shown earlier in the presentation; [11C]PiB binds to amyloid plaques, and can thus be used to quantify amyloid burden in neurodegenerative disorders such as Alzheimer’s disease (AD); This enables use of amyloid PET for clinical trial enrichment and monitoring response of subjects to experimental anti-amyloid therapy. 2. Nitrogen-13 Production and Properties  Production Source Half-life 16O(p,𝛂)13N [13N]NOx 9.96 min 13N 13C(p,n)13N [13N]NH3 Nitrogen-13 Decay Mode Decay Product Application β+ (99.80%) 13C PET EC (0.20%)  Nitrogen-13 target is filled with 16OH2– 16O(p,) 13N  -p a rtic le p ro to n N -1 4 16O C 13- N1 1 Target generates [13N]NOX or, if spiked with EtOH or over- pressurized with CH4, [13N]NH3 Nitrogen-13 Radiochemistry  1. Synthesis of [13N]NH3 Reduction [13N]NOx [13N]NH3 In target reduction CH4 over pressure EtOH EtOH/H2 etc. Lab reduction Davarda’s Alloy  [13N]NH3 Synthesis Modules Apparatus for production of Module for processing [13N]NH3 [13N]NH3 using Devarda’s alloy generated in target 2. Other Radiochemistry with 13N EJNMMI Radiopharmacy and Chemistry 2, Article number: 16 (2017) Examples of13N-Labeled Radiopharmaceuticals  [13N]NH3 PET imaging is used for assessing both relative and absolute myocardial blood flow; [13N]NH3 (10-20 mCi; 370-740 MBq) is administered intravenously. Imaging begins 4 min after injection to allow for pulmonary background activity clearance. To diagnose coronary artery disease (CAD), a 2nd study is performed after physical or [13N]NH3 myocardial perfusion imaging: The stress study shows pharmacological stress. extensive hypoperfusion of the anterior lateral, lateral, inferior- lateral, and inferior wall. The rest study shows normal perfusion. See: Nuclear Medicine by Ziessman, O'Malley Thrall (Eds), 4th Edition, 2014 3. Oxygen-15 Production and Properties  Production Source Half-life 14N(d,n)15O 15O [15O]O2 122.24 sec [13N]NH3 Oxygen-15 Decay Mode Decay Product Application β+ (100) 15N PET Oxygen-15 Radiochemistry [15O]H2O [15O]H2O can be produced by initial production of [15O]O2 by irradiation with deuterons (14N(d,n)15O) or protons (16O(p,pn)15O). [15O]H2O is then produced using palladium- or platinum-catalyzed reactions of [15O]O2 with H2 at elevated temperatures. [15O]Butanol Examples of15O-Labeled Radiopharmaceuticals 15O-Labeled Radiopharmaceuticals [15O]Water Blood flow [15O]CO Blood volume [15O]O2 Oxygen Extraction Picchio and Castellucci, Theranostics 2012 Representative reconstruction images, scatter-corrected by HDE & DEC, for 15O-H2O, 15O-O2, and 15O-CO from a patient with the stenosis of the left internal carotid artery and with three typical slice positions. HDE hybrid dual-energy-window scatter correction, DEC deconvolution scatter correction Ibaraki, Annals of Nuclear Medicine, 2016 4. Iodine-124 Production and Properties  Production Source Half-life 124Te(p,n)124I 124I [124I]NaI 4.2 days Iodine-124 Decay Mode Decay Product Application β+ (26%) 124Te PET EC (74%) Koehler et al., Molecules, 2010 Iodine-124 Radiochemistry Nucleophilic Methods Electrophilic Methods a) [124I]NaI, Iodogen®, 5% HOAc in MeOH, DMSO, room temperature, 10 min; b) TFA. Koehler et al., Molecules, 2010 Examples of124I-Labeled Radiopharmaceuticals Multiple pulmonary lesions evidenced by the 124I-MIBG PET/CT Maximum Intensity Projection (MIP) image (A) and the posterior views of 131I-MIBG post-therapy scan acquired 24 h (B) and 48 h (C) after injection Koehler et al., Molecules, 2010; Cistaro, Nucl Med Rev, 2015. 5. Summary  Carbon-11; Nitrogen-13; Oxygen-15 and Iodine-124 are useful isotopes for PET imaging; There have been significant research efforts aimed at developing methods for both their production and incorporation into bioactive molecules; This has led to the introduction of many PET radiotracers with advanced imaging applications in neurology, oncology and cardiology.