Nanoparticles and phage display selected peptides for imaging and therapy of cancer.

Molecular imaging probes are a special class of pharmaceuticals that target specific biochemical signatures associated with disease and allow for noninvasive imaging on the molecular level. Because changes in biochemistry occur before diseases reach an advanced stage, molecular imaging probes make it possible to locate and stage disease, track the effectiveness of drugs, treat disease, monitor response, and select patients to allow for more personalized diagnosis and treatment of disease. Targeting agents radiolabeled with positron emitters are of interest due to their ability to quantitatively measure biodistribution and receptor expression to allow for optimal dose determinations. (68)Ga is a positron emitter, which allows for quantitative imaging through positron emission chromatography (PET). The availability of (68)Ga from a generator and its ability to form stable complexes with a variety of chelates hold promise for expanding PET utilization to facilities unable to afford their own cyclotron. Nanoparticles conjugated with various proteins and peptides derived from phage display that can be selectively targeted are being developed and evaluated for guided imaging and therapy. Herein we highlight some initial efforts in combining the enhanced selectivity of nanoparticles and peptides with (68)Ga for use as molecular imaging probes.

Geographic Disparities in Re-triage Destinations Among Seriously Injured Californians.

Objective: To quantify geographic disparities in sub-optimal re-triage of seriously injured patients in California. Summary of Background Data: Re-triage is the emergent transfer of seriously injured patients from the emergency departments of non-trauma and low-level trauma centers to, ideally, high-level trauma centers. Some patients are re-triaged to a second non-trauma or low-level trauma center (sub-optimal) instead of a high-level trauma center (optimal). Methods: This was a retrospective observational cohort study of seriously injured patients, defined by an Injury Severity Score > 15, re-triaged in California (2009-2018). Re-triages within one day of presentation to the sending center were considered. The sub-optimal re-triage rate was quantified at the state, regional trauma coordinating committees (RTCC), local emergency medical service agencies, and sending center level. A generalized linear mixed-effects regression quantified the association of sub-optimality with the RTCC of the sending center. Geospatial analyses demonstrated geographic variations in sub-optimal re-triage rates and calculated alternative re-triage destinations. Results: There were 8,882 re-triages of seriously injured patients and 2,680 (30.2 %) were sub-optimal. Sub-optimally re-triaged patients had 1.5 higher odds of transfer to a third short-term acute care hospital and 1.25 increased odds of re-admission within 60 days from discharge. The sub-optimal re-triage rates increased from 29.3 % in 2009 to 38.6 % in 2018. 56.0 % of non-trauma and low-level trauma centers had at least one sub-optimal re-triage. The Southwest RTCC accounted for the largest proportion (39.8 %) of all sub-optimal re-triages in California. Conclusion: High population density geographic areas experienced higher sub-optimal re-triage rates.

Gum arabic-coated radioactive gold nanoparticles cause no short-term local or systemic toxicity in the clinically relevant canine model of prostate cancer.

INTRODUCTION: Gum arabic-coated radioactive gold nanoparticles (GA-(198)AuNPs) offer several advantages over traditional brachytherapy in the treatment of prostate cancer, including homogenous dose distribution and higher dose-rate irradiation. Our objective was to determine the short-term safety profile of GA-(198)AuNPs injected intralesionally. We proposed that a single treatment of GA-(198)AuNPs would be safe with minimal-to-no evidence of systemic or local toxicity. METHODS: Nine dogs with spontaneously occurring prostatic cancer were treated. Injections were performed with ultrasound or computerized tomography guidance. Complete blood counts, chemistry panels, and urinalyses were performed at weekly intervals for 1 month and imaging was repeated 4 weeks postinjection. Planar scintigraphic images were obtained within 30 minutes of injection. RESULTS: No statistically significant difference was found in any hematologic or biochemical parameter studied, nor was any evidence of tumor swelling or abscessation found in eight dogs with repeat imaging; one dog died secondary to urethral obstruction 12 days following injection. At 30 minutes postinjection, an average of 53% of injected dose in seven dogs was retained in the prostate, with loss of remaining activity in the bladder and urethra; no systemic uptake was detected. CONCLUSION: GA-(198)AuNP therapy had no short-term toxicity in the treatment of prostatic cancer. While therapeutic agent was found in the prostate immediately following injection, some loss of agent was detected in the bladder and urethra. Localization of radioactivity within the prostate was lower than anticipated and likely due to normal vestigial prostatic ducts. Therefore, further study of retention, dosimetry, long-term toxicity, and efficacy of this treatment is warranted prior to Phase I trials in men.