Hot or not? Investigating radiation safety and policy updating for the appropriate storage of radioactive specimens at Mount Sinai Hospital.

PURPOSE: The current hospital policy for this study is stringent regarding the storage of radioactive sentinel lymph node (SLN) specimens, which requires the storage time of 24 hours before being handled by Pathology. Additional labeling along with separate containment of these specimens can be forgone if negligible radiation levels are found. The objective of this study was to determine whether the storage time needed for resected radioactive breast and primary site specimens to decay to twice the background radiation levels is less than 24 hours. METHODS: The investigators retrieved breast and primary site SLN specimens from the Pathology department on the same day of the biopsy. A dose calibrator was used to measure the dose, specimen, and concurrent background radioactivity in Megabecquerels (MBq). Radioactive decay calculations were used to further investigate when specimen activities reached twice the background levels. A retrospective analysis was performed using a one-sample t-test to determine if the time to reach double the background activity was significantly different from 24 hours. This study pertained to workflow optimization; thus, general procedure consent forms were sufficient. Both patient confidentiality and privacy were protected. The investigators followed the necessary radiation safety measures. RESULTS: The mean time for specimens to reach twice the background level of radioactivity was 3.99 hours, significantly less than current storage time of 24 hours (p < 0.001). The mean time point for the SLNs to reach 1/16th of the original activity was 7.78 hours (p < 0.001). The average node activity was 0.14 MBq. CONCLUSION: The average sentinel node activity was less than 1 exemption quantity and the time to reach less than twice the background levels was significantly less than 24 hours, meaning that radioactive labels are not needed, and the 24-hour overnight specimen storage can be mitigated.

Development of nuclear medicine image quality assessment criteria for use in a technologist peer review program.

INTRODUCTION/BACKGROUND: A peer learning program includes the process of peer review, which is the act of performing a secondary review of a peer's work using pre-defined criteria. The Technologist Image Quality Assessment Criteria Project (TIQACP) was initiated to develop and evaluate such criteria for use by technologists for assessment of image quality in Nuclear Medicine (NM). METHODS: A NM clinical expert panel was assembled, comprising 14 technologists, radiologists, and educators from five imaging centres and an academic institution with associated medical imaging training programs. Project design was guided by consensus-based methodology that included three phases: (1) image quality assessment criteria development, based on literature search and expert review (2) image quality assessment criteria refinement, based on consensus-building exercises (panel surveys, discussions, ranking exercise, and time trial) (3) external validation performed via a national survey of NM technologists, facilitated by the Canadian Association of Medical Radiation Technologists. RESULTS: The first phase generated 8 key evidence sources, including textbooks, NM journals and guidelines from professional associations that were reviewed by the expert panel leads and led to a preliminary list of 11 criteria. As part of the second phase, the preliminary list was reviewed via online surveys and panel discussions. Preliminary discussions led to an initial expansion of the list to include 18 criteria. This list required an average of 9 min (range: 7-11 min) for review, which was deemed prohibitive by the panel. A ranking exercise identified 'all required anatomy is clearly identified' as the most relevant criteria and 'Image quality demonstrates no breakdown of the radiopharmaceutical' as the least relevant criteria. Panel discussion also highlighted need to eliminate criteria that were not applicable to all settings. These insights led to an updated list of nine criteria organized into four categories. National validation was supported by 47 NM technologists from across Canada. Respondents were in agreement that the criteria reflected the core elements of image quality in NM (94% agree to strongly agree), were familiar (97%) and were relevant to their current practice setting (88%). The final list was thus not changed based on the survey. DISCUSSION/CONCLUSION: The TIQACP utilized an inclusive process that engaged a range of subject matter experts and the broader NM community to ensure buy-in of the final criteria. These criteria have subsequently been embedded in peer review software that has been implemented into a robust peer learning program for technologists designed to promote a culture of continuous improvement and knowledge sharing amongst front-line staff.

Differential Actions of Estrogen Receptor α and ß via Nongenomic Signaling in Human Prostate Stem and Progenitor Cells.

Human prostate stem and progenitor cells express estrogen receptor (ER)α and ERß and exhibit proliferative responses to estrogens. In this study, membrane-initiated estrogen signaling was interrogated in human prostate stem/progenitor cells enriched from primary epithelial cultures and stem-like cell lines from benign and cancerous prostates. Subcellular fractionation and proximity ligation assays localized ERα and ERß to the cell membrane with caveolin-1 interactions. Exposure to 17ß-estradiol (E2) for 15 to 60 minutes led to sequential phosphorylation of signaling molecules in MAPK and AKT pathways, IGF1 receptor, epidermal growth factor receptor, and ERα, thus documenting an intact membrane signalosome that activates diverse downstream cascades. Treatment with an E2-dendrimer conjugate or ICI 182,870 validated E2-mediated actions through membrane ERs. Overexpression and knockdown of ERα or ERß in stem/progenitor cells identified pathway selectivity; ERα preferentially activated AKT, whereas ERß selectively activated MAPK cascades. Furthermore, prostate cancer stem-like cells expressed only ERß, and brief E2 exposure activated MAPK but not AKT cascades. A gene subset selectively regulated by nongenomic E2 signaling was identified in normal prostate progenitor cells that includes BGN, FOSB, FOXQ1, and MAF. Membrane-initiated E2 signaling rapidly modified histone methyltransferases, with MLL1 cleavage observed downstream of phosphorylated AKT and EZH2 phosphorylation downstream of MAPK signaling, which may jointly modify histones to permit rapid gene transcription. Taken together, the present findings document ERα and ERß membrane-initiated signaling in normal and cancerous human prostate stem/progenitor cells with differential engagement of downstream effectors. These signaling pathways influence normal prostate stem/progenitor cell homeostasis and provide novel therapeutic sites to target the elusive prostate cancer stem cell population.

Influence of pirfenidone on airway hyperresponsiveness and inflammation in a Brown-Norway rat model of asthma.

Pirfenidone was administered to sensitized Brown Norway rats prior to a series of ovalbumin challenges. Airway hyperresponsiveness, inflammatory cell infiltration, mucin and collagen content, and the degree of epithelium and smooth muscle staining for TGF-beta were examined in control, sensitized, and sensitized/challenged rats fed a normal diet or pirfenidone diet. Pirfenidone had no effect on airway hyperresponsiveness, but reduced distal bronchiolar cell infiltration and proximal and distal mucin content. Statistical analysis showed that the control group and sensitized/challenged pirfenidone diet group TGF-beta staining intensity scores were not significantly different from isotype controls, but that the staining intensity scores for the sensitized/challenged normal diet group was significantly different from isotype controls. These results suggest that pirfenidone treatment is effective in reducing some of the components of acute inflammation induced by allergen challenge.