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INTRODUCTION: Prostate cancer (PCa) is the second most common cause of cancer related death in men. Accurate diagnosis of bone metastases is essential to treatment decision-making and follow-up. Recent primary studies have compared the accuracy of 68Ga-PSMA PET/CT versus 99mTc-MDP bone scintigraphy in the detection of PCa bone metastases. These studies suggest 68Ga-PSMA PET/CT to be superior. Comprehensive syntheses of these studies are now warranted. PURPOSE: To synthesize studies comparing the accuracy of 68Ga-PSMA PET/CT versus 99mTc-MDP bone scintigraphy, the most used modality in the identification of bone metastases in PCa patients. METHODS: A systematic review was conducted evaluating diagnostic accuracy studies which compared 68Ga-PSMA PET/CT and 99mTc-MDP bone scintigraphy. Bias and quality were assessed using the QUADAS-2 tool. Searches in three databases using search terms: Positron-Emission Tomography, prostatic neoplasm, 68Ga, and bone were conducted. Image acquisitions between modalities had to be performed within 3 months of each other. RESULTS: Five single-centered studies were included in this review. Across all measures of accuracy, 68Ga PSMA PET/CT was superior to 99mTc-MDP bone scintigraphy in the detection of skeletal metastases. Patient-based sensitivities and specificities across included studies ranged from (91%-100% vs. 50%-91%) and (88%-100% vs 19%-96%) for 68Ga-PSMA PET/CT and 99mTc-MDP bone scintigraphy respectively. The overall risk of bias was moderate primarily due to the retrospective nature of most included studies. CONCLUSION: 68Ga-PSMA PET/CT was more accurate than 99mTc-MDP bone scintigraphy in the detection of PCa bone metastases. Future studies should seek to define the clinical relevance of these findings.

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Unsymmetrically disubstituted metallocene derivatives, characterized as the first sandwich structure, have found interest in asymmetrical synthesis and in medicinal chemistry as well. Besides, they present a particular case of chirality. Twenty original and six commercially available molecules presenting either i) a planar chirality or ii) an asymmetrical carbon containing group or iii) being symmetrically substituted were analyzed in supercritical fluid chromatography on eleven polysaccharide-based chiral stationary phases with carbon dioxide containing 30% of methanol or 2-propanol as a co-solvent mobile phase. A basic additive, either diethylamine, triethylamine or n-butylamine was also required at 1% to the co-solvent for elution. While some of the tested chiral stationary phases provided enantioseparation for the racemates, chlorinated cellulosic phases proved to be both highly retentive and highly enantioselective towards these particular species with the highest rate of success compared to their non-chlorinated counterparts. For instance, the resolution value was equal to 14.1 for one ferrocene derivative in one-hour analysis time on cellulose tris(3,5-dichlorophenylcarbamate) column with 30% 2-propanol/1% n-butylamine while a single peak was observed under the same conditions on cellulose tris(3,5-dimethylphenylcarbamate) column. Experimental parameters were arbitrarily set at 150 bar outlet pressure, 40 °C temperature and 3 mL/min flow-rate.

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Maleimide chemistry is widely used in the site-selective modification of proteins. However, hydrolysis of the resultant thiosuccinimides is required to provide robust stability to the bioconjugates. Herein, we present an alternative approach that affords simultaneous stabilisation and dual functionalisation in a one pot fashion. By consecutive conjugation of a thiol and an amine to dibromomaleimides, we show that aminothiomaleimides can be generated extremely efficiently. Furthermore, the amine serves to deactivate the electrophilicity of the maleimide, precluding further reactivity and hence generating stable conjugates. We have applied this conjugation strategy to peptides and proteins to generate stabilised trifunctional conjugates. We propose that this stabilisation-dual modification strategy could have widespread use in the generation of diverse conjugates.