Kiel Neumann, PhD
University of California San Francisco
"Dynamic" Molecular Imaging: A Tale of Two Stories (more ...)
"Dynamic" Molecular Imaging: A Tale of Two Stories (hide ...)
CounterACTing Chemical Warfare with PET
The use of organophosphorus compounds (OP), such as sarin gas, as chemical weapons continues to be a significant threat to both military personnel and citizens. The lethality of these ?weapons of mass destruction? arises from OP potent inhibition of acetylcholinesterase (AChE), which, if not treated immediately (seconds to minutes), leads to paralysis and ultimately, death. To date, a single class of oxime compounds, such as 2PAM, is the only clinically approved treatment for OP toxicity and at physiological pH, the charged nature of these oximes renders them ineffective CNS penetrants. The main bottleneck for advancing countermeasures for the OP toxidrome is a lack of mechanism-based pharmacokinetic and pharmacodynamic (PK/PD) analyses that cannot efficiently quantitate and verify relative amounts of OP, OP-AChE adduct, and/or oxime antidote in peripheral
circulation and the CNS. We have developed four positron-labeled OP nerve agents and a positron-labeled analogue of 2PAM and have used the agents to understand the OP toxidrome in vivo through dynamic PET imaging with concomitant arterial sampling. Moving forward, we aim to expand this methodology to allow external investigators to discern critical in vivo PK distribution, PD attributes and localization of the AChE target in appropriate animal models and ultimately, strengthen and/or
develop new antidotes for OP toxicity.
GKX: A sugar substitute for cancer?
Lung cancer is responsible for the most cancer-related mortalities worldwide. Of the nearly 225,000 new cases of lung cancer in 2016, 85% will be classified as nonsmall cell lung cancer (NSCLC). Chemotherapy remains a major treatment modality and the only adjuvant therapy proven to prolong patient survival after surgical resection. Major advances in early-stage diagnostics have been made within the last 10 years, along with discoveries of novel biomarkers, which have formed the basis for targeted therapies based on oncogene/tumor suppressor status. However, to date, the 5-year survival rate for NSCLC remains marginal at 19%. The high mortality rate is due, in part, to the high molecular heterogeneity observed in NSCLC, which obfuscates correlating targetable driver mutations with chemotherapy response, leaving systemic chemotherapy as the frontline adjuvant therapy option. The lung cancer field would gain significantly by the availability of a non-invasive tool that could stratify early-stage NSCLC patients who are most likely to relapse after surgical resection; furthermore, guide the clinician on whether a systemic chemotherapy drug, such as cisplatin, will provide any relevant change in the patient?s 5-year survival rate and overall survival compared to a more targeted molecular therapy.
Frontiers of Biomedical Imaging Science, VUIIS Classroom (Room AA1119)