The use of RNAi to suppress protein synthesis offers a potential way of reducing the level of enzymes or the synthesis of mutant toxic proteins but there are few tools currently available for their delivery. To address this problem, bioconjugated quantum dots (QDs) containing a hydrophobic component (N-palmitate) and a sequence VKIKK designed to traverse across cell membranes and visualize drug delivery were developed and tested on cell lines of brain origin. We used the Zn outer shell of the QD to bind HIS6 in JB577 (W•G•Dap(N-Palmitoyl)•VKIKK•P9•G2•H6) and by a gel-shift assay showed that siRNAs would bind to the positively charged KIKK sequence. By comparing many peptides and QD coatings, we showed that the QD-JB577-siRNA construct was taken up by cells of nervous system origin, distributed throughout the cytosol, and inhibited protein synthesis, implying that JB577 was also promoting endosome egress. By attaching siRNA for luciferase in a cell line over-expressing luciferase, we showed 70% inhibition of mRNA after 24–48 h. To show more specific effects, we synthesized siRNA for neutral (NSMase2), acid (lysosomal ASMase) sphingomyelinase, and sphingosine kinase 1 (SK1), we demonstrated a dose-dependent inhibition of activity. These data suggest that QDs are a useful siRNA delivery tool and QD-siRNA could be a potential theranostic for a variety of diseases.

No abstract

The identification of cN1 disease at 68GaP-SMA-PET/CT was associated with lower risk of BCR likely due to better accuracy of this imaging modality in detecting micro-metastatic disease which may allow for the identification of an earlier node positive stage with a better prognosis.

e17007 Background: Prostate-specific membrane antigen (PSMA) is overexpressed on most prostate cancers (PCs), a fact that has been exploited to perform both targeted imaging and treatment. PSMA-based PET imaging allows for more sensitive detection of PC and can be useful even in the context of negative CT and bone scans. Prior to 2021, research protocols using PSMA-PET (PET) were common at large academic centers, but will likely be more commonplace as standard of care (SOC) after recent FDA approval. With a change in SOC imaging, the impact of cost to patients must be examined. We hypothesize that socioeconomic and demographic-based care disparities may widen and access may narrow in the face of these changes. Methods: We collected demographic data on patients with PC from Weill Cornell Medicine (WCM), Brooklyn Methodist Hospital (BMH), and Columbia University Medical Center (CUMC) who received a PSMA PET scan between 1 January 2018 and 31 January 2022. Data collected included age, zip code, primary language, self-reported race and ethnicity, and type of insurance coverage. Zip codes were used to estimate income strata of patients using publicly-available 2018 IRS adjusted gross income (AGIs) as follows ($): < 25k, 25k-50k, 50k-75k, 75k-100k, 100k-200k, and > 200k. Any AGI strata comprising > 20% of population was counted. Patients were divided into four cohorts: those who had a scan (1) as part of therapeutic-based studies for mCRPC, (2) non-therapeutic imaging studies, (3) as a part of a cost-recovery study with an out-of-pocket cost of $1054, and (4) commercial use under post-approval standards of care (SOC) billed to insurance. Proportion of self-reported race in each cohort was compared against overall race distribution for prostate cancer registry from WCM and CUIMC (Table). Results: 896 patients underwent PSMA PET. Approximately half of all scans were in Cohort 4 (49%, n = 368) including all BMH scans. CUMC scans were 90% in Cohort 2 (122/136). In Cohort 1, 2, and 3, > 90% of subjects resided in zip codes with AGI > $100k. In Cohort 4, 84% resided in zip codes with AGI > $100k. Overall 70.4% of subjects identified as White, 8.3% Black or African American, 3.5% Asian, 4.4% Other, and 13.5% were unknown/or declined. African American/Black was most represented on Cohort 4 (11%), and least represented in Cohort 1 (5%). Conclusions: White patients comprise the largest proportion or PET scans whereas non-white groups are underrepresented across all cohorts. Access to PETs has appeared to improve for lower AGI, non-white patients following FDA approval and insurance coverage. It will be critical to assure equitable access across all demographic groups as deployment of PET scanning becomes the new standard of care.[Table: see text]