C-11 Radiochemistry in Cancer Imaging Applications
Division of Radiological Sciences, Washington University School of Medicine, Campus Box 8225, 510 S. Kingshighway Blvd., St. Louis, MO 63110, USA. Current topics in medicinal chemistry
(Impact Factor: 3.4).
04/2010; 10(11):1060-95. DOI: 10.2174/156802610791384261
Carbon-11 (C-11) radiotracers are widely used for the early diagnosis of cancer, monitoring therapeutic response to cancer treatment, and pharmacokinetic investigations of anticancer drugs. PET imaging permits non-invasive monitoring of metabolic processes and molecular targets, while carbon-11 radiotracers allow a "hot-for cold" substitution of biologically active molecules. Advances in organic synthetic chemistry and radiochemistry as well as improved automated techniques for radiosynthesis have encouraged investigators in developing carbon-11 tracers for use in oncology imaging studies. The short half-life of carbon-11 (20.38 minutes) creates special challenges for the synthesis of C-11 labeled tracers; these include the challenges of synthesizing C-11 target compounds with high radiochemical yield, high radiochemical purity and high specific activity in a short time and on a very small scale. The optimization of conditions for making a carbon-11 tracer include the late introduction of the C-11 isotope, the rapid formation and purification of the target compound, and the use of automated systems to afford a high yield of the target compound in a short time. In this review paper, we first briefly introduce some basic principles of PET imaging of cancer; we then discuss principles of carbon-11 radiochemistry, focus on specific advances in radiochemistry, and describe the synthesis of C-11 radiopharmaceuticals developed for cancer imaging. The carbon-11 radiochemistry approaches described include the N,O, and S-alkylations of [(11)C]methyl iodide/[(11)C]methyl triflate and analogues of [(11)C]methyl iodide and their applications for making carbon-11 tracers; we then address recent advances in exploring a transmetallic complex mediated [(11)C]carbonyl reaction for oncologic targets.
Available from: Qi-Huang Zheng
- "While studying the reported methods for [ 18 F]PBR06 production, we designed the fully automated synthesis of [ 11 C]PBR06 (Fig. 1), a carbon-11 labeled form of PBR06, for the first time. Compared to fluorine-18 tracers (half-life 110 min), carbon-11 tracers (half-life 20 min) have some advantages in back-to-back same-day PET studies such as allowing a patient to receive multiple C-11 injections to shorten the diagnostic process when multiple tracer studies are required, and in reducing the radiation exposure for both radiopharmaceutical production staff and environment  . We also discovered a new labeling precursor, the previously undescribed tosylate congener of PBR06 with better tosyloxy leaving group, and investigated a fully automated synthesis of [ 18 F]PBR06. "
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ABSTRACT: The translocator protein 18 kDa (TSPO) is an attractive target for molecular imaging of neuroinflammation and tumor progression. [(18)F]PBR06, a fluorine-18 labeled form of PBR06, is a promising PET TSPO radioligand originally developed at NIMH. [(11)C]PBR06, a carbon-11 labeled form of PBR06, was designed and synthesized for the first time. The standard PBR06 was synthesized from 2,5-dimethoxybenzaldehyde in three steps with 71% overall chemical yield. The radiolabeling precursor desmethyl-PBR06 was synthesized from 2-hydroxy-5-methoxybenzaldehyde in five steps with 12% overall chemical yield. The target tracer [(11)C]PBR06 was prepared by O-[(11)C]methylation of desmethyl-PBR06 with [(11)C]CH(3)OTf in CH(3)CN at 80°C under basic condition and isolated by HPLC combined with SPE purification with 40-60% decay corrected radiochemical yield and 222-740 GBq/μmol specific activity at EOB. On the similar grounds, [(18)F]PBR06 was also designed and synthesized. The previously described Br-PBR06 precursor was synthesized from 2,5-dimethoxybenzaldehyde in two steps with 78% overall chemical yield. A new radiolabeling precursor tosyloxy-PBR06, previously undescribed tosylate congener of PBR06, was designed and synthesized from ethyl 2-hydroxyacetate, 4-methylbenzene-1-sulfonyl chloride, and N-(2,5-dimethoxybenzyl)-2-phenoxyaniline in four steps with 50% overall chemical yield. [(18)F]PBR06 was prepared by the nucleophilic substitution of either new tosyloxy-PBR06 precursor or known Br-PBR06 precursor in DMSO at 140°C with K[(18)F]F/Kryptofix 2.2.2 for 15 min and HPLC combined with SPE purification in 20-60% decay corrected radiochemical yield, >99% radiochemical purity, 87-95% chemical purity, and 37-222 GBq/μmol specific activity at EOB. Radiosynthesis of [(18)F]PBR06 using new tosylated precursor gave similar radiochemical purity, and higher specific activity, radiochemical yield and chemical purity in comparison with radiosynthesis using bromine precursor.
Steroids 07/2011; 76(12):1331-40. DOI:10.1016/j.steroids.2011.06.012 · 2.64 Impact Factor
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ABSTRACT: Optical constants (refractive index, n, and absorption index, k) of the as-deposited and annealed films of 5,10,15,20-tetraphenyl-21H, 23H-porphine iron (III) chloride (FeTPPCl) have been obtained in the wavelength range 190–2500 nm by using spectrophotometric measurements. The obtained optical constants were used to estimate the type of transition for the as-deposited and annealed films. We present a single oscillator model that describes the dispersion of refractive index. Drude model of free carriers absorption have been described for the analysis the dispersion of refractive index dispersion before and after annealing.
Materials Chemistry and Physics 01/2011; 125(1-2):247-251. DOI:10.1016/j.matchemphys.2010.09.017 · 2.26 Impact Factor
Available from: Rodney Hicks
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ABSTRACT: For the evaluation of biological processes using radioisotopes, there are two competing technologies: single-photon emission computed tomography (SPECT) and positron emission tomography (PET). Both are tomographic techniques that enable 3D localization and can be combined with CT for hybrid imaging. PET-CT has clear technical superiority including superior resolution, speed and quantitative capability. SPECT-CT currently has greater accessibility, lower cost and availability of a wider range of approved radiotracers. However, the past decade has seen dramatic growth in PET-CT with decreasing costs and development of an increasing array of PET tracers that can substitute existing SPECT applications. PET-CT is also changing the paradigm of imaging from lesion measurement to lesion characterization and target quantification, supporting a new era of personalized cancer therapy. The efficiency and cost savings associated with improved diagnosis and clinical decision-making provided by PET-CT make a cogent argument for it becoming the dominant molecular technique in oncology.
Nature Reviews Clinical Oncology 11/2012; 9(12). DOI:10.1038/nrclinonc.2012.188 · 14.18 Impact Factor
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