Pilot performance of a dedicated prostate PET suitable for diagnosis and biopsy guidance

[EN] Background: Prostate cancer (PCa) represents one of the most common types of cancers facing the male population. Nowadays, to confirm PCa, systematic or multiparametric MRI-targeted transrectal or transperineal biopsies of the prostate are required. However, due to the lack of an accurate imaging technique capable to precisely locate cancerous cells in the prostate, ultrasound biopsies sample random parts of the prostate and, therefore, it is possible to miss regions where those cancerous cells are present. In spite of the improvement with multiparametric MRI, the low reproducibility of its reading undermines the specificity of the method. Recent development of prostatespecific radiotracers has grown the interest on using positron emission tomography (PET) scanners for this purpose, but technological improvements are still required (current scanners have resolutions in the range of 4¿5 mm). Results: The main goal of this work is to improve state-of-the-art PCa imaging and diagnosis. We have focused our efforts on the design of a novel prostate-dedicated PET scanner, named ProsPET. This system has small scanner dimensions defined by a ring of just 41 cm inner diameter. In this work, we report the design, implementation, and evaluation (both through simulations and real data) of the ProsPET scanner. We have been able to achieve < 2 mm resolution in reconstructed images and high sensitivity. In addition, we have included a comparison with the Philips Gemini-TF scanner, which is used for routine imaging of PCa patients. The ProsPET exhibits better contrast, especially for rod sizes as small as 4.5 mm in diameter. Finally, we also show the first reconstructed image of a PCa patient acquired with the ProsPET. Conclusions: We have designed and built a prostate specific PET system, with a small footprint and improved spatial resolution when compared to conventional whole-body PET scanners. The gamma ray impact within each detector block includes accurate DOI determination, correcting for the parallax error. The potential role of combined organdedicated prostate-specific membrane antigen (PSMA) PET and ultrasound devices, as a prebiopsy diagnostic tool, could be used to guide sampling of the most aggressive sites in the prostate.The work presented in this article has been partially funded by a research grant from the regional government of the Comunitat Valenciana (Spain), co-funded by the European Union ERDF funds (European Regional Development Fund) of the Comunitat Valenciana 2014-2020, with reference IDIFEDER/2018/032 (High-Performance Algorithms for the Modelling, Simulation and early Detection of diseases in Personalized Medicine). This project has also received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 695536). It has also been supported by the EU Grant 603002 under the FP7 program and by the Spanish Ministerio de Economia, Industria y Competitividad under Grant e and through PROSPET (DTS15/00152) funded by the Ministerio de Economia y Competitividad.Cañizares-Ledo, G.; Gonzalez-Montoro, A.; Freire, M.; Lamprou, E.; Barrio, J.; Sánchez Martínez, F.; Benlloch Baviera, JM.... (2020). Pilot performance of a dedicated prostate PET suitable for diagnosis and biopsy guidance. EJNMMI Physics. 7(1):1-17. https://doi.org/10.1186/s40658-020-00305-yS11771GLOBOCAN 2018. http://www.gco.iarc.fr/today/ datasources-methods. Accessed 26 Dec 2019.Ferlay J, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN. Int J Cancer. 2012;2015:136–E359.Rawla P. Epidemiology of prostate cancer. 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The impact of the alkyne substitution pattern and metalation on the photo-isomerization of azobenzene-based platinum(II) diynes and polyynes

Trimethylsilyl-protected dialkynes incorporating azobenzene linker groups, Me₃SiCCRCCSiMe₃ (R = azobenzene-3,3′-diyl, azobenzene-4,4′-diyl, 2,5-dioctylazobenzene-4,4′-diyl), and the corresponding terminal dialkynes, HCCRCCH, have been synthesized and characterized. The CuI-catalyzed dehydrohalogenation reaction between <i>trans</i>-[Ph­(Et₃P)₂PtCl] and the deprotected dialkynes in a 2:1 ratio in ⁱPr₂NH/CH₂Cl₂ gives the platinum­(II) diynes <i>trans</i>-[Ph­(Et₃P)₂PtCCRCCPt­(PEt₃)₂Ph], while the dehydrohalogenation polycondensation reaction between <i>trans</i>-[(ⁿBu₃P)₂PtCl₂] and the dialkynes in a 1:1 molar ratio under similar reaction conditions affords the platinum­(II) polyynes, [−Pt­(PⁿBu₃)₂–CCRCC−]_<i>n</i>. The materials have been characterized spectroscopically, with the diynes also studied using single-crystal X-ray diffraction. The platinum­(II) diynes and polyynes are all soluble in common organic solvents. Optical-absorption measurements show that the compounds incorporating the <i>para</i>-alkynylazobenzene spacers have a higher degree of electronic delocalisation than their <i>meta</i>-alkynylazobenzene counterparts. Reversible photoisomerization in solution was observed spectroscopically for the alkynyl-functionalized azobenzene ligands and, to a lesser extent, for the platinum­(II) complexes. Complementary quantum-chemical modeling was also used to analyze the optical properties and isomerization energetics

Dicopper(I) Complexes Incorporating Acetylide-functionalized Pyridinyl-based Ligands::Synthesis, Structural and Photovoltaic Studies

Heteroaryl incorporated acetylide-functionalized pyridinyl ligands (<b>L1–L6</b>) with the general formula Py-CC-Ar (Py = pyridine and Ar = <i>thiophene-2-yl</i>, 2,2′<i>-bithiophene]-5-yl</i>, 2,2′<i>:5</i>′,2″<i>-terthiophene]-5-yl</i>, <i>thieno­[2,3-<i>b</i>]­thiophen-2-yl</i>, <i>quinoline-5-yl</i>, <i>benzo­[c]­[1,2,5]­thiadiazole-5-yl</i>) have been synthesized by Pd(0)/Cu­(I)-catalyzed cross-coupling reaction of 4-ethynylpyridine and the respective heteroaryl halide. Ligands <b>L1–L6</b> were isolated in respectable yields and characterized by microanalysis, IR spectroscopy, ¹H NMR spectroscopy, and ESI-MS mass spectrometry. A series of dinuclear Cu­(I) complexes <b>1</b>–<b>10</b> have been synthesized by reacting <b>L1–L6</b> with CuI and triphenylphosphine (PPh₃) (<b>R1</b>) or with an anchored phosphine derivative, 4-(diphenylphosphino) benzoic acid (<b>R2</b>)/2-(diphenylphosphino)­benzenesulfonic acid (<b>R3</b>), in a stoichiometric ratio. The complexes are soluble in common organic solvents and have been characterized by analytical, spectroscopic, and computational methods. Single-crystal X-ray structure analysis confirmed rhomboid dimeric structures for complexes <b>1</b>, <b>2</b>, <b>4</b>, and <b>5</b>, and a polymeric structure for <b>6</b>. Complexes <b>1</b>–<b>6</b> showed oxidation potential responses close to 0.9 V vs Fc^0/+, which were chemically irreversible and are likely to be associated with multiple steps and core oxidation. Preliminary photovoltaic (PV) results of these new materials indicated moderate power conversion efficiency (PCE) in the range of 0.15–1.56% in dye-sensitized solar cells (DSSCs). The highest PCE was achieved with complex <b>10</b> bearing the sulfonic acid anchoring functionality

Data for "The Impact of the Alkyne Substitution Pattern and Metallation on the Photo-isomerization of Azobenzene-based Platinum(II) Di-ynes and Poly-ynes"

Data from the computational modelling described in the article "The Impact of the Alkyne Substitution Pattern and Metallation on the Photo-isomerization of Azobenzene-based Platinum(II) Di-ynes and Poly-ynes". Includes optimised molecular structures, vibrational frequencies, electronic excitation level, simulated infrared (IR) and absorption spectra, and assignments of the electronic transitions

CCDC 828207: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures