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Abstract Background The positron emitting isotope fluorine-18 (18F) possesses almost ideal physicochemical properties for the development of radiotracers for diagnostic molecular imaging employing positron emission tomography (PET). 18F in its nucleophilic anionic 18F− form is usually prepared by bombarding an enriched 18O water target with protons of various energies between 5 and 20 MeV depending on the technical specifications of the cyclotron. Large thick-target yields between 5 and 14 GBq/µA can be obtained, enough to prepare large batches of radiotracers capable to serve a considerable contingent of patients (50 + per clinical batch). The overall yield of the radiotracer however depends on the efficiency of the 18F labeling chemistry. The Silicon Fluoride Acceptor chemistry (SiFA) has introduced a convenient and highly efficient way to provide clinical peptide-based 18F-radiotracers in a kit-like procedure matching the convenience of 99mTc radiopharmaceuticals. Main body A radiotracer’s clinical success primarily hinges on whether its synthesis can be automated. Due to its simplicity, the SiFA chemistry, which is based on isotopic exchange (18F for 19F), does not only work in a manual setup but has been proven to be automatable, yielding large batches of 18F-radiotracers of high molar activity (Am). The production of SiFA radiotracer can be centralized and the radiopharmaceutical be distributed via the “satellite” principle, where one production facility economically serves multiple clinical application sites. Clinically validated tracers such as [18F]SiTATE and [18F]Ga-rhPSMA-7/-7.3 have been synthesized in an automated synthesis unit under good manufacturing practice conditions and used in large patient cohorts. Communication of common guidelines and practices is warranted to further the dissemination of SiFA radiopharmaceuticals and to give easy access to this technology. Conclusion This current review highlights the most recent achievements in SiFA radiopharmaceutical automation geared towards large batch production for clinical application. Best practice advice and guidance towards a facilitated implementation of the SiFA technology into new and already operating PET tracer production facilities is provided. A brief outlook spotlights the future potential of SiFA radiochemistry within the landscape of non-canonical labeling chemistries.

PurposeSomatostatin analogues (SSA) are frequently used in the treatment of neuroendocrine tumours. Recently, [18F]SiTATE entered the field of somatostatin receptor (SSR) positron emission tomography (PET)/computed tomography (CT) imaging. The purpose of this study was to compare the SSR-expression of differentiated gastroentero-pancreatic neuroendocrine tumours (GEP-NET) measured by [18F]SiTATE-PET/CT in patients with and without previous treatment with long-acting SSAs to evaluate if SSA treatment needs to be paused prior to [18F]SiTATE-PET/CT.Methods77 patients were examined with standardised [18F]SiTATE-PET/CT within clinical routine: 40 patients with long-acting SSAs up to 28 days prior to PET/CT examination and 37 patients without pre-treatment with SSAs. Maximum and mean standardized uptake values (SUVmax and SUVmean) of tumours and metastases (liver, lymphnode, mesenteric/peritoneal and bones) as well as representative background tissues (liver, spleen, adrenal gland, blood pool, small intestine, lung, bone) were measured, SUV ratios (SUVR) were calculated between tumours/metastases and liver, likewise between tumours/metastases and corresponding specific background, and compared between the two groups.ResultsSUVmean of liver (5.4 ± 1.5 vs. 6.8 ± 1.8) and spleen (17.5 ± 6.8 vs. 36.7 ± 10.3) were significantly lower (p < 0.001) and SUVmean of blood pool (1.7 ± 0.6 vs. 1.3 ± 0.3) was significantly higher (p < 0.001) in patients with SSA pre-treatment compared to patients without. No significant differences between tumour-to-liver and specific tumour-to-background SUVRs were observed between both groups (all p > 0.05).ConclusionIn patients previously treated with SSAs, a significantly lower SSR expression ([18F]SiTATE uptake) in normal liver and spleen tissue was observed, as previously reported for 68Ga-labelled SSAs, without significant reduction of tumour-to-background contrast. Therefore, there is no evidence that SSA treatment needs to be paused prior to [18F]SiTATE-PET/CT.

The incorporation of silicon fluoride acceptor (SiFA) moieties into a variety of molecules, such as peptides, proteins and biologically relevant small molecules, has improved the generation of 18F-radiopharmaceuticals for medical imaging. The efficient isotopic exchange radiofluorination process, in combination with the enhanced [18F]SiFA in vivo stability, make it a suitable strategy for fluorine-18 incorporation. This review will highlight the clinical applicability of [18F]SiFA-labeled compounds and discuss the significant radiotracers currently in clinical use.

The reaction of sodium chloride with 2-[bis(2-hydroxyethyl)amino]ethan-1-ol results in the formation of the title salt {[Na{N(CH2CH2OH)3}]Cl}n. The polymeric structure is characterized by a sodium cation coordinated by one nitrogen and five oxygen atoms in a distorted octahedral environment. The resulting one-dimensional {—O—Na—O—Na—O}— coordination polymer extends parallel to [010] and is connected through the chloride counter-anion via O—H...Cl hydrogen bonding, giving rise to a two-dimensional supramolecular structure parallel to (001).

The crystal structure, including a graph-set analysis, of 1-[(2-hydroxy-2-methylpropyl)methylamino]-2-methylpropan-2-ol, C9H21NO2, is reported. The structure is characterized by unsymmetrical intra- and intermolecular O—H...O hydrogen bridges, giving rise to the formation of an infinite polymer consisting of eight-membered rings arranged in zigzag chains running along the a axis.

The synthesis, radiolabeling and in vitro evaluation of new silicon-fluoride acceptor (SiFA) derivatized D2-receptor ligands is reported. The SiFA-technology simplifies the introduction of fluorine-18 into target specific biomolecules for Positron-Emission-Tomography (PET). However, one of the remaining challenges, especially for small molecules such as receptor-ligands, is the bulkiness of the SiFA-moiety. We therefore synthesized four Fallypride SiFA-conjugates derivatized either directly at the benzoic acid ring system (SiFA-DMFP, SiFA-FP, SiFA-DDMFP) or at the butyl-side chain (SiFA-M-FP) and tested their receptor affinities. We found D2-receptor affinities for all compounds in the nanomolar range (Ki(SiFA-DMFP) = 13.6 nM, Ki(SiFA-FP) = 33.0 nM, Ki(SiFA-DDMFP) = 62.7 nM and Ki(SiFA-M-FP) = 4.21 nM). The radiofluorination showed highest yields when 10 nmol of the precursors were reacted with [18F]fluoride/TBAHCO3 in acetonitrile. After a reversed phased cartridge purification the desired products could be isolated as an injectable solution after only 10 min synthesis time with radiochemical yields (RCY) of more than 40% in the case of SiFA-DMFP resulting in specific activities >41 GBq/µmol (>1,100 Ci/mmol). Furthermore, the radiolabeled products were shown to be stable in the injectable solutions, as well as in human plasma, for at least 90 min.

The asymmetric unit of the title compound, C15H25FOSi, contains two independent molecules. Each of the Si atoms approximates the expected tetrahedral geometry with Si—F bond lengths of 1.6128 (11) and 1.6068 (11) Å in the two independent molecules. In the crystal, supramolecular chains along a are found mediated by O—H...O hydrogen bonds.

In the title 2:1 adduct, [Sn2W2(C10H13NO2)2(CO)10]2[W(CO)6], the complete hexacarbonyltungsten molecule is generated by a crystallographic inversion centre. The heterometallic molecule features a central Sn2O2 core with essentially equal Sn—Oethoxy bond lengths. The second ethoxy O and amine N atoms of each N,O,O′-tridentate ligand coordinate to one Sn atom only. The NO3 donor atoms occupy basal positions and the W atom the apical position in a distorted square-pyramidal geometry for each Sn atom. The W atoms are approximately syn to each other but the central metal core is non-planar [W—Sn...Sn—W pseudo-torsion angle = 43.573 (16)°]. One of the carbonyl ligands in the heterometallic molecule is disordered over two orientations with equal occupancies. In the crystal, the heterometallic molecules associate via C—H...O interactions, forming supramolecular layers with undulating topology in the ab plane. These stack along the c axis, defining voids which are occupied by the W(CO)6 molecules.

The synthesis of the intramolecularly coordinated heteroleptic organostannylene tungsten pentacarbonyl complexes 4-tBu-2,6-[P(O)(OiPr)2]2C6H2Sn(X)W(CO)5(1, X = Cl; 2, X = F; 3, X = PPh2) and of 4-tBu-2,6-[P(O)(OiPr)2]2C6H2Sn[W(CO)5]PPh2[W(CO)5], 4, are reported. UV-irradiation of compound 4in tetrahydrofurane serendipitously gave the bis(organostannylene) tungsten tetracarbonyl complex cyclo-O2W[OSn(R)]2W(CO)4(R= 4-tBu-2,6-[P(O)(OiPr)2]2C6H2), 5, that contains an unprecedented W(0)–Sn–O–W(vi) bond sequence. The compounds 1–5were characterized by means of single crystal X-ray diffraction analysis, 1H, 13C, 19F, 31P, 119Sn NMR, and IR spectroscopy, electrospray ionization mass spectrometry (ESI–MS), and elemental analysis. Compound 4features a hindered rotation about the Sn–P bond. [ABSTRACT FROM AUTHOR]

An intramolecular O–H⋯F hydrogen bridge involving a methanol molecule provides communication between the strongly separated sodium cation and fluoride anion in sodium fluoride that is, for the first time and despite its high lattice energy, ditopically complexed by an organotin-substituted crown ether. [ABSTRACT FROM AUTHOR]