The diagnostic accuracy of O-(2-18F-fluoroethyl)-L-tyrosine parameters for the differentiation of brain tumour progression from treatment-related changes.

BACKGROUND: 18F-fluoro-ethyl-tyrosine (18F-FET) is recommended to distinguish brain tumours post-therapeutic true progression (including recurrent and metastatic brain tumours) and treatment-related change (TRC). However, many parameters of 18F-FET can be used for this differential diagnosis. Our purpose was to investigate the diagnostic accuracy of various 18F-FET parameters to differentiate true progression from TRC. METHODS: We performed a literature search using the following databases: the PubMed, Embase and Web of Science databases up to 29 November 2020. We included studies that reported the diagnostic test results of 18F-FET to distinguish true progression from TRC. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to evaluate the quality of the included studies. The diagnostic accuracy of various parameters was pooled using a random-effects model. RESULTS: We included 17 eligible studies (nine parameters). For static parameters of 18F-FET, the maximum and mean tumour-to-brain ratios (TBRmax and TBRmean) showed similar pooled sensitivities of 82% [95% confidence interval (CI), 80-85%) and 82% (95% CI, 78-85%), respectively. Among the three kinetic parameters (slope, time to peak and kinetic pattern), the kinetic pattern presented the optimal diagnostic value with a pooled sensitivity of 81% (95% CI, 75-86%). When combining the static and kinetic parameters, the diagnostic performance of 18F-FET was significantly improved, with a pooled sensitivity of 90% (95% CI, 84-94%) in the combination of TBR and kinetic patterns. CONCLUSIONS: 18F-FET static parameters alone showed a comparably high sensitivity in the differentiation between brain tumour true progression and TRC. Combining static and kinetic parameters provided improved diagnostic performance.

Strategic Design of Amyloid-ß Species Fluorescent Probes for Alzheimer's Disease.

Alzheimer's disease (AD) is a high mortality and high disability rates neurodegenerative disease characterized by irreversible progression and poses a significant social and economic burden throughout the world. However, currently approved AD therapeutic agents only alleviate symptoms and there is still a lack of practical therapeutic regimens to stop or slow the progression of this disease. Thus, there is urgently needed novel diagnosis tools and drugs for early diagnosis and treatment of AD. Among several AD pathological hallmarks, amyloid-ß (Aß) peptide deposition is considered a critical initiating factor in AD. In recent years, with the advantages of excellent sensitivity and high resolution, near-infrared fluorescence (NIRF) imaging has attracted the attention of many researchers to develop Aß plaque probes. This review mainly focused on different NIRF probe design strategies for imaging Aß species to pave the way for the future design of novel NIRF probes for early diagnosis AD.

Isonitrile induced bioorthogonal activation of fluorophores and mutually orthogonal cleavage in live cells.

Fluorophores with different emission wavelengths were efficiently quenched by a tert-butyl terminated tetrazylmethyl group and activated by an isonitrile-tetrazine click-to-release reaction. Nucleic acid templated chemistry significantly accelerated this bioorthogonal cleavage. Moreover, two mutually orthogonal fluorogenic cleavage reactions were simultaneously conducted in live cells for the first time.

Impact of 68 Gallium prostate-specific membrane antigen tracers on the management of patients with prostate cancer who experience biochemical recurrence.

OBJECTIVE: To investigate the impact of 68 Gallium prostate-specific membrane antigen (68 Ga-PSMA) tracers on the management of prostate cancer (PCa) patients with biochemical recurrence (BCR) by conducting a systematical review and meta-analysis. MATERIALS AND METHODS: We performed a literature search of the PubMed, Embase and Web of Science databases up to 29 October 2019. We included studies that reported the proportion of patients whose management changed after 68 Ga-PSMA tracers were used in patients with BCR. We used the Quality Assessment of Diagnostic Accuracy Studies-2 tool to evaluate the quality of the included studies. The proportion of patients with management changes were pooled using a random-effects model. Subgroup analyses and meta-regression analyses were performed to explore the source of heterogeneity. A Sankey diagram was used to show treatment change from before to after the use of 68 Ga-PSMA tracers. RESULTS: We included 20 eligible studies (2026 patients). The pooled proportion of patients with management change was 53% (95% confidence interval [CI] 46-60) in patients with BCR and 51% (95% CI, 34-67) in patients with early BCR (prostate-specific antigen [PSA] <0.5 ng/mL). The pooled positron-emission tomography-positive rate in patients with BCR was 68% (95% CI 59-78). Fourteen studies reported management change, with most changes being intermodal in nature (42%, vs 17% intramodal change). CONCLUSIONS: The use of 68 Ga-PSMA tracers altered the management of more than half of PCa patients with BCR, including those with early BCR. 68 Ga-PSMA tracers might be used to guide individualized treatment in patients with BCR, particularly those with early BCR.

Organocatalytic and Scalable Syntheses of Unsymmetrical 1,2,4,5-Tetrazines by Thiol-Containing Promotors.

Despite the growing application of tetrazine bioorthogonal chemistry, it is still challenging to access tetrazines conveniently from easily available materials. Described here is the de novo formation of tetrazine from nitriles and hydrazine hydrate using a broad array of thiol-containing catalysts, including peptides. Using this facile methodology, the syntheses of 14 unsymmetric tetrazines, containing a range of reactive functional groups, on the gram scale were achieved with satisfactory yields. Using tetrazine methylphosphonate as a building block, a highly efficient Horner-Wadsworth-Emmons reaction was developed for further derivatization under mild reaction conditions. Tetrazine probes with diverse functions can be scalably produced in yields of 87-93 %. This methodology may facilitate the widespread application of tetrazine bioorthogonal chemistry.

D-T7 Peptide-Modified PEGylated Bilirubin Nanoparticles Loaded with Cediranib and Paclitaxel for Antiangiogenesis and Chemotherapy of Glioma.

The blood-brain tumor barrier (BTB) and blood-brain barrier (BBB) have always been the major barriers in glioma therapy. In this report, we proposed D-T7 peptide-modified nanoparticles actively targeted glioma by overcoming the BBB and BTB to improve the antiglioma efficacy. Glioma-targeting experiments showed that the penetration effect of the D-T7 peptide-modified nanoparticles was 7.89-fold higher than that of unmodified nanoparticles. Furthermore, cediranib (CD) and paclitaxel (PTX) were used for the combination of the antiangiogenesis and chemotherapy for glioma. PEGylated bilirubin nanoparticles (BRNPs) were selected as a suitable drug delivery system (CD&PTX@TBRBPs) owing to the antioxidant, anti-inflammatory, and reactive oxygen species-responsive ability. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and apoptosis assays showed that CD&PTX@TBRBPs had the highest cytotoxicity and the median survival time of the CD&PTX@TBRNP group was 3.31-fold and 1.23-fold longer than that of the saline and CD&PTX@BRNP groups, respectively. All the results showed that we constructed a novel and accessible peptide-modified dual drug carrier with an enhanced antiglioma effect.