[en] Introduction: An automated method is described for the rapid and high-yield synthesis of two of the most commonly used radioactive fatty acids: [¹¹C]acetate and [¹¹C]palmitate. Methods: Reaction of [¹¹C]CO₂ with the respective Grignard reagents in diethyl ether solution proceeded for 2 min at 40°C. Quenching of the reaction and liberation of nonreacted [¹¹C]CO₂ occurred upon addition of a fourfold molar excess of aqueous 0.1 M HCl (acetate) or nonaqueous HCl/Et₂O (palmitate). Labeled products were then purified by adsorption to an Alumina-N Sep-Pak Plus cartridge and eluted with either aqueous NaH₂PO₄ solution (acetate) or 100% ethanol (palmitate). Results: High-performance liquid chromatography analysis confirmed that the radiochemical purity of each product was >98%, and decay-corrected radiochemical yields averaged 33% for [¹¹C]palmitate and 40% for [¹¹C]acetate. Conclusion: The method requires no liquid–liquid extraction, solvent evaporation or distillation capabilities and can be readily adapted to existing radiosynthesis modules.

[en] [¹¹C]Choline has been evaluated as a potential positron emission tomography (PET) marker for imaging of breast cancer. The biodistribution of [¹¹C]choline was determined at 45 min post iv injection in MCF-7's transfected with IL-1alpha implanted athymic mice and MDA-MB-435 implanted athymic mice. The results showed the uptake of [¹¹C]choline in these tumors was high, 2.0% dose/g in MCF-7's transfected with IL-1alpha implanted mice and 1.8% dose/g in MDA-MB-435 implanted mice; the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were 1.7 (T/M, MCF-7's), 2.1 (T/M, MDA-MB-435) and 6.9 (T/B, MCF-7's), 12.5 (T/B, MDA-MB-435), respectively; the tumor/muscle ratios are moderate, and the tumor/blood ratios are high. The micro-PET imaging of [¹¹C]choline in both breast cancer athymic mice was acquired for 15 min from a MCF-7's transfected with IL-1alpha and/or MDA-MB-435 implanted mouse at 45 min post iv injection of 1 mCi of the tracer using a dedicated high resolution (<3 mm full-width at half-maximum) small FOV (field-of-view) PET imaging system, Indy-PET II scanner, developed in our laboratory, which showed the uptake of [¹¹C]choline in MCF-7's transfected with IL-1alpha tumor or MDA-MB-435 tumor implanted in a nude athymic mouse. These results suggest that [¹¹C]choline may be a potential PET breast cancer imaging agent

[en] Highlights: • Facile radiosynthesis of [¹⁸F]FET was performed by a two-step one-pot method using a home-built fully automated multi-purpose ¹⁸F-radiosynthesis module. • [¹⁸F]FET was produced with reasonable radiochemical yield and overall synthesis time; and high radiochemical purity, molar activity and enantiomeric purity. • New radio-analytical RP-HPLC methods were developed for synthesis monitoring and quality control of [¹⁸F]FET. • The radiopharmaceutical [¹⁸F]FET meets all quality control criteria for human brain tumor imaging application. - Abstract: O-(2-[¹⁸F]Fluoroethyl)-_l-tyrosine ([¹⁸F]FET) has become one of the most successful amino acid tracers for human brain tumor imaging with positron emission tomography (PET). Facile fully automated radiosynthesis and quality control (QC) of [¹⁸F]FET using our home-built automated multi-purpose ¹⁸F-radiosynthesis module are described. [¹⁸F]FET was produced in 75–80 min overall synthesis time with 20–25% radiochemical yield decay corrected to end of bombardment (EOB), based on H[¹⁸F]F. The radiochemical and enantiomeric purities were >99%, and the molar activity (A_m) was 189–411 GBq/μmol at EOB. The [¹⁸F]FET dose meets all QC criteria for clinical use, and is suitable for clinical PET study of brain tumor.

[en] (2R)-2-[[4-(6-fluorohex-1-ynyl)phenyl]sulfonylamino]-3-methylbutyric acid [¹¹C]methyl ester ([¹¹C]FMAME), a novel carbon-11 labeled matrix metalloproteinase (MMP) inhibitor, has been synthesized for evaluation as new potential positron emission tomography (PET) cancer biomarker. [¹¹C]FMAME was prepared by appropriate precursor (2R)-2-[[4-(6-fluorohex-1-ynyl)phenyl]sulfonylamino]-3-methylbutyric acid (FMA), which was synthesized in six steps from (D)-valine in 71% chemical yield. This acid precursor was labeled by [¹¹C]methyl triflate through O-[¹¹C]methylation method under basic conditions and isolated by solid-phase extraction (SPE) purification to produce pure target compound in 40-55% radiochemical yield, based on ¹¹CO₂, decay corrected to end of bombardment, and 15-20 min synthesis time. The biodistribution of [¹¹C]FMAME was determined at 30 min post IV injection in breast cancer animal models MCF-7 transfected with IL-1α implanted athymic mice and MDA-MB-435 implanted athymic mice. The results showed the uptakes of [¹¹C]FMAME in these tumors were 1.13% dose/g in MCF-7 transfected with IL-1α implanted mice and 1.37% dose/g in MDA-MB-435 implanted mice, respectively; the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were 1.05 ± 0.29 (T/M, MCF-7's), 0.77 ± 0.20 (T/B, MCF-7's) and 0.99 ± 0.35 (T/M, MDA-MB-435), 1.44 ± 0.69 (T/B, MDA-MB-435), respectively. Pretreatment of MCF-7 transfected with IL-1α tumor-bearing mice with MMP inhibitor FMA had no effect on [¹¹C]FMAME biodistribution. Likewise, pretreatment of MDA-MB-435 tumor-bearing mice with FMA also showed no effect on [¹¹C]FMAME biodistribution. The micro-PET images were acquired for 15 min from a MCF-7 transfected with IL-1α tumor-bearing mouse or a MDA-MB-435 tumor-bearing mouse at 30 min post IV injection of 1 mCi of [¹¹C]FMAME using a dedicated high resolution (<3 mm full-width at half-maximum) PET imaging system (Indy-PET II scanner). The initial dynamic micro-PET images of [¹¹C]FMAME in a MCF-7 transfected with IL-1α tumor-bearing mouse during different time periods of 0-15, 15-30, 30-45 and 45-60 min were performed by Indy-PET II. The PET images clearly showed both tumors were visible with [¹¹C]FMAME. These results suggest that the localization of [¹¹C]FMAME in the tumor is mediated by non-specific processes, and the visualization of [¹¹C]FMAME on the tumor using the Indy-PET II scanner is related to non-specific binding

[en] Highlights: • A new P2X7R radioligand [¹⁸F]IUR-1602 was synthesized. • A 2-step 2-pot fully automated [¹⁸F]-radiosynthesis for [¹⁸F]IUR-1602 was developed. • A semi-preparative RP HPLC-SPE technique was employed in radiosynthesis. • K_i value of IUR-1602 was 23.6 ± 0.96 nM. - Abstract: The overexpression of P2X7R is associated with neuroinflammation and plays an important role in various neurodegenerative diseases. The [¹⁸F]fluoropropyl derivative of GSK1482160, [¹⁸F]IUR-1602, has been first prepared and examined as a new potential P2X7R radioligand. The reference standard IUR-1602 was synthesized from tert-butyl (S)-5-oxopyrrolidine-2-carboxylate, fluoropropylbromide, and 2-chloro-3-(trifluoromethyl)benzylamine with overall chemical yield 13% in three steps. The target tracer [¹⁸F]IUR-1602 was synthesized from desmethyl-GSK1482160 with 3-[¹⁸F]fluoropropyl tosylate, prepared from propane-1,3-diyl bis(4-methylbenzenesulfonate) and K[¹⁸F]F/Kryptofix2.2.2, in two steps and isolated by HPLC combined with SPE in 2–7% decay corrected radiochemical yield. The radiochemical purity was >99%, and the molar activity at end of bombardment (EOB) was 74–370 GBq/μmol. The potency of IUR-1602 in comparison with GSK1482160 was determined by a radioligand competitive binding assay using [¹¹C]GSK1482160, and the binding affinity K_i values for IUR-1602 and GSK1482160 are 23.6 and 3.07 nM, respectively. The initial in vitro evaluation results, 8-fold less potency of [¹⁸F]IUR-1602 compared to [¹¹C]GSK1482160, prevent further in vivo evaluation of [¹⁸F]IUR-1602 in animals and human.

[en] Improved syntheses of dopamine D₂/D₃ receptor radioligands [¹¹C]Fallypride and [¹⁸F]Fallypride are reported. The phenolic precursor (9) for C-11 labeling and the Fallypride (10) reference standard were synthesized from the starting material 2-hydroxy-3-methoxy-5-(2-propenyl)benzoic acid methyl ester (1) in 7 and 8 steps with 16% and 5% overall chemical yields, respectively. The tosylated precursor (15) for F-18 labeling was synthesized from compound 1 in 5 steps with 32% overall chemical yield. An alternate synthetic approach for Fallypride has been developed using the same starting material 1 in 5 steps with 26% overall chemical yield. [¹¹C]Fallypride ([¹¹C]10) was prepared by O-[¹¹C]methylation of the phenolic precursor with [¹¹C]methyl triflate and purified with a semi-preparative HPLC method in 50-60% radiochemical yield, decay corrected to end of bombardment (EOB), based on [¹¹C]CO₂, and 370±185 GBq/μmol specific radioactivity at EOB. [¹⁸F]Fallypride ([¹⁸F]10) was prepared by nucleophilic substitution of the tosylated precursor with K[¹⁸F]F/Kryptofix 2.2.2 and HPLC combined with solid-phase extraction (SPE) purification in variable (up to 50%) decay corrected radiochemical yield from K[¹⁸F]F and 111-222 GBq/μmol specific activity at EOB.