Search

Abstract: The use of a polymeric solid support loaded with a long alkyl chain quaternary ammonium allows the rapid and efficient recovery of cyclotron produced [18F]F− from [18O]water to a low water content organic solution compatible with fast nucleophilic labelling of most precursors for PET radiopharmaceuticals in high yield. [Copyright &y& Elsevier]

Abstract: A fast and reliable method suitable for the automated preparation of (substituted) [18F]fluorobenzyl halides from several [18F]fluorobenzaldehydes was developed. Aromatic nucleophilic substitution of trimethylammonium benzaldehyde triflate and nitro precursors was realized with no-carrier-added [18F]fluoride. After labeling, fluorine-18 containing aldehydes were trapped on a Solid Phase Extraction (SPE) cartridge and the subsequent conversion into benzyl halide was directly realized, on-line, on the support. Reduction of the aldehydes (>95%) was near-quantitative with an aqueous solution of NaBH4. Halogenation was performed on the same support with different aqueous solutions of concentrated acid (HI, HBr, HCl). The conversion of benzyl alcohols into [18F]fluorobenzyl halides (X=Cl, Br, I) usually proceeded within 2min at high yields. The halogenation proceeded at room temperature, with the exception of the 2-[18F]fluoro-3-methoxybenzyl, 2- and 4-[18F]fluorobenzyl halides, which required the use of HBr/HOAc (33%). With this method, various [18F]fluorobenzyl chloride, bromide and iodide compounds were obtained with high radiochemical purities (>90%) and with overall radiochemical yields of 15–70%. The radiosynthesis was completed in 30 or 45min from EOB, starting from the ammonium or nitro precursor, respectively. By using the same solid support, 2- and 4-[18F]fluorobenzyl bromide and iodide derivatives were near-quantitatively converted (>95%) into the corresponding azido compounds (60°C, 5min). As the reduction and halogenation steps were performed on solid supports, automation of the whole synthesis was straightforward. [Copyright &y& Elsevier]

Abstract: Two new silicon-based prosthetic groups, derived from 3-[ethoxybis(1-methylethyl)silyl]propanamine, have been prepared in good yields. These silicon groups bearing an acid or an azide group were coupled to a model tripeptide (Leu-Gly-Gly) either through a classical amide bond formation or through “click chemistry” via the Huisgen cycloaddition. The radiolabelling with fluorine-18 by substitution of the ethoxy group at silicon has been carried out with success in 51–54% decay corrected radiochemical yields. Radiolabelled peptides were easily prepared by direct 18F-fluorination of the silicon-bearing tripeptide or by coupling the peptide with a radiolabelled silicon-based prosthetic group. Their stabilities in physiological medium were studied and proved poor. [Copyright &y& Elsevier]

We herein describe the straightforward synthesis of a stable pyridyl(4-methoxyphenyl)iodonium salt and its [ 18 F] radiolabeling within a one-step, fully automated and cGMP compliant radiosynthesis of [ 18 F]UCB-H ([ 18 F]7), a PET tracer for the imaging of synaptic vesicle glycoprotein 2A (SV2A). Over the course of 1 year, 50 automated productions provided 34 ± 2% of injectable [ 18 F]7 from up to 285 GBq (7.7 Ci) of [ 18 F]fluoride in 50 min (uncorrected radiochemical yield, specific activity of 815 ± 185 GBq/μmol). The successful implementation of our synthetic strategy within routine, high-activity, and cGMP productions attests to its practicality and reliability for the production of large doses of [ 18 F]7. In addition to enabling efficient and cost-effective clinical research on a range of neurological pathologies through the imaging of SV2A, this work further demonstrates the real value of iodonium salts for the cGMP 18 F-PET tracer manufacturing industry, and their ability to fulfill practical and regulatory requirements in that field.

Objective: To evaluate the accuracy of ¹⁸F-fluoride PET/computed tomography (CT) to detect bone metastases (BMs) in a breast and prostate cancer population, using magnetic resonance imaging (MRI) or thin-slice CT as a gold standard., Methods: We have prospectively included 34 patients with breast (N=24) or prostate cancer (N=10) at high risk of BMs. Whole-body PET/CT (low-dose CT) and bone scintigraphy (BS) with single photon emission CT were obtained for all 34 patients and the results compared with a radiological gold standard., Results: Out of the 386 foci detected by PET/CT, 219 (56.7%) could be verified by CT or MRI. Eighty-six additional foci were detected by BS (n=46) or seen only by CT (n=9), MRI (n=23), or both CT and MRI (n=8). The total number of verified lesions was therefore 274 (58.1%), including 119 (43.4%) benign and 155 (56.6%) BM. The sensitivity, specificity, and accuracy of ¹⁸F-fluoride PET/CT were 76, 84.2, and 80%, respectively. For BS, they were 44.8, 79.2, and 60%, respectively. Sensitivity significantly decreased for the lytic lesions. The accuracy of PET/CT was significantly superior to BS for pelvic and lumbar lesions. PET/CT provided a correct diagnosis (M+/M0) in 32 of 33 patients (one false positive) compared with 28 of 33 with BS (four false positive, one false positive)., Conclusion: ¹⁸F-fluoride PET/CT is significantly more accurate than BS for detecting BMs from breast and prostate cancers.

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We used voxel-based Statistical Parametric Mapping (SPM) approaches to characterize the functional neuroanatomy of the vegetative state. The most dysfunctional brain regions were bilateral frontal and parieto-temporal associative cortices. Despite the metabolic impairment, external stimulation still induced a significant neuronal activation (i.e., change in blood flow) in vegetative patients as shown by both auditory click stimuli and noxious somatosensory stimuli. However, this activation was limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we demonstrated that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction.