Mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) are commonly found in gliomas. AGI-5198, a potent and selective inhibitor of the mutant IDH1 enzyme, was radiolabeled with radioiodine and fluorine-18. These radiotracers were evaluated as potential probes for imaging mutant IDH1 expression in tumors with positron emission tomography (PET). Radioiodination of AGI-5198 was achieved using a tin precursor in 79 ± 6% yield (n = 9), and F-labeling was accomplished by the Ugi reaction in a decay-corrected radiochemical yield of 2.6 ± 1.6% (n = 5). The inhibitory potency of the analogous nonradioactive compounds against mutant IDH1 (IDH1-R132H) was determined in enzymatic assays. Cell uptake studies using radiolabeled AGI-5198 analogues revealed somewhat higher uptake in IDH1-mutated cells than that in wild-type IDH1 cells. The radiolabeled compounds displayed favorable tissue distribution characteristics in vivo, and good initial uptake in IDH1-mutated tumor xenografts; however, tumor uptake decreased with time. Radioiodinated AGI-5198 exhibited higher tumor-to-background ratios compared withF-labeled AGI-5198; unfortunately, similar results were observed in wild-type IDH1 tumor xenografts as well, indicating lack of selectivity for mutant IDH1 for this tracer. These results suggest that AGI-5198 analogues are not a promising platform for radiotracer development. Nonetheless, insights gained from this study may help in design and optimization of novel chemical scaffolds for developing radiotracers for imaging the mutant IDH1 enzyme.
Background: HIV preexposure prophylaxis (PrEP) remains underutilized despite its efficacy and potential population impact. Achieving PrEP's full potential depends on providers who are knowledgeable and comfortable prescribing it to individuals at risk of acquiring HIV. Previous educational interventions targeting provider-related uptake barriers have had limited success. We designed and tested an electronic medical record (EMR) interpretative comment to improve the delivery of PrEP.Methods: An EMR comment provided information on PrEP eligibility and referral resources to providers delivering positive chlamydia and gonorrhea results. Positive test results for bacterial sexually transmitted infections before intervention (January 1, 2019-August 23, 2019) and after intervention (August 24, 2019-December 31, 2019) were identified. A retrospective chart review was conducted to ascertain provider documentation of PrEP discussions or provision, HIV prevention discussions, and HIV screening. Pretest-posttest analysis was performed to compare the provision of PrEP and HIV prevention services.
Results:We reviewed 856 preintervention encounters spanning 8 months and 461 postencounters spanning 4 months. Patient demographics were comparable. We observed an increase in provider documentation of safe sex and condom counseling (odds ratios [ORs], 1.2 [95% confidence interval {CI}, 1.07-1.18] and 1.11 [95% CI, 1.05-1.17], respectively), and the absence of any HIV prevention discussion decreased (OR, 0.85; 95% CI, 0.80-0.90), but not HIV screening or PrEP documentation.
Conclusions:We demonstrated that an EMR laboratory comment had a modest effect on increasing risk reduction counseling, although not HIV screening or PrEP prescriptions. Future strategies to encourage provider delivery of sexual health services may benefit from more targeted strategies that combine behavioral and information technology approaches.
Multiplex PCR testing for gastrointestinal pathogens was performed on a longitudinal cohort of 110 MSM taking HIV PrEP. At least one pathogen was detected among 50 (45%) participants, with some participants testing positive for the same pathogen on multiple consecutive visits over a period of months.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.