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1.  Prostate Specific Kallikrein-related Peptidases and Their Relation to Prostate Cancer Biology and Detection; Established Relevance and Emerging Roles 
Thrombosis and haemostasis  2013;110(3):484-492.
The kallikreins are a family of serine proteases with a range of tissue-specific and essential proteolytic functions. Among the most well-studied are the prostate tissue specific KLK2 and KLK3 genes and their secreted protease products, hk2 and PSA. Members of the so-called classic kallikreins, these highly active trypsin-like serine proteases play established roles in human reproduction. Both hK2 and PSA expression is regulated by the androgen receptor, whose activity has a fundamental role in prostate tissue development and progression of disease. This feature, combined with the ability to sensitively detect different forms of these proteins in blood and biopsies, result in a crucially important biomarker for the presence and recurrence of cancer. Emerging evidence has begun to suggest a role for these kallikreins in critical vascular events. This review discusses the established and developing biological roles of hK2 and PSA, as well as the historical and advanced use of their detection to accurately and non-invasively detect and guide treatment of prostatic disease.
doi:10.1160/TH13-04-0275
PMCID: PMC4029064  PMID: 23903407
2.  Quantitative imaging of disease signatures through radioactive decay signal conversion 
Nature medicine  2013;19(10):1345-1350.
In the era of personalized medicine there is an urgent need for in vivo techniques able to sensitively detect and quantify molecular activities. Sensitive imaging of gamma rays is widely used, but radioactive decay is a physical constant and signal is independent of biological interactions. Here we introduce a framework of novel targeted and activatable probes excited by a nuclear decay-derived signal to identify and measure molecular signatures of disease. This was accomplished utilizing Cerenkov luminescence (CL), the light produced by ╬▓-emitting radionuclides such as clinical positron emission tomography (PET) tracers. Disease markers were detected using nanoparticles to produce secondary Cerenkov-induced fluorescence. This approach reduces background signal compared to conventional fluorescence imaging. In addition to information from a PET scan, we demonstrate novel medical utility by quantitatively determining prognostically relevant enzymatic activity. This technique can be applied to monitor other markers and facilitates a shift towards activatable nuclear medicine agents.
doi:10.1038/nm.3323
PMCID: PMC3795968  PMID: 24013701
Activatable probes; Molecular imaging; Nanoparticles; Cerenkov luminescence
3.  Cerenkov imaging - a new modality for molecular imaging 
Cerenkov luminescence imaging (CLI) is an emerging hybrid modality that utilizes the light emission from many commonly used medical isotopes. Cerenkov radiation (CR) is produced when charged particles travel through a dielectric medium faster than the speed of light in that medium. First described in detail nearly 100 years ago, CR has only recently applied for biomedical imaging purposes. The modality is of considerable interest as it enables the use of widespread luminescence imaging equipment to visualize clinical diagnostic (all PET radioisotopes) and many therapeutic radionuclides. The amount of light detected in CLI applications is significantly lower than other that in other optical imaging techniques such as bioluminescence and fluorescence. However, significant advantages include the use of approved radiotracers and lack of an incident light source, resulting in high signal to background ratios. As well, multiple subjects may be imaged concurrently (up to 5 in common bioluminescent equipment), conferring both cost and time benefits. This review summarizes the field of Cerenkov luminescence imaging to date. Applications of CLI discussed include intraoperative radionuclide-guided surgery, monitoring of therapeutic efficacy, tomographic optical imaging capabilities, and the ability to perform multiplexed imaging using fluorophores excited by the Cerenkov radiation. While technical challenges still exist, Cerenkov imaging has materialized as an important molecular imaging modality.
PMCID: PMC3477724  PMID: 23133811
Cerenkov radiation; PET; optical imaging; fluorescence

Results 1-3 (3)