Accession Number : ADA597872


Title :   Imaging of Oxidative Stress in Prostate Cancer


Descriptive Note : Final rept. 27 Sep 2012-26 Sep 2013


Corporate Author : MEMORIAL SLOAN-KETTERING CANCER CENTER NEW YORK


Personal Author(s) : Zeglis, Brian M


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a597872.pdf


Report Date : Oct 2013


Pagination or Media Count : 10


Abstract : The purpose of this grant was the synthesis, development, and validation of a PET imaging agent for the non-invasive delineation of hydrogen peroxide (H2O2) levels in prostate cancer. We are seeking such an imaging agent because the over-production of hydrogen peroxide in prostate tumors has been linked to with rapid tumor cell proliferation, aggressive tumor growth, and enhanced metastatic ability. We believe that the project has the potential to be paradigm-shifting, as it would be the first PET agent for the in vivo delineation of cellular H2O2 production. The central hypothesis of the project is that the selective, H2O2- mediated cleavage of carbon-boron bonds could be used as the centerpiece of a strategy for the PET imaging of H2O2. The majority of the work during this funding period was dedicated to elucidating and executing a synthetic route to an 18F-radiolabeled probe containing an H2O2-sensitive carbon-boron bond. Unfortunately, the short radioactive half-life and reactivity with boron of 18F ultimately combined with the instability of alkyne-bearing boronates to click chemistry conditions to preclude the synthesis of such an agent. Toward the end of the funding period, we turned to a different positron-emitting radioisotope, 124I, and were subsequently able to synthesize an 124I-labeled, boronate ester-containing probe 124I-hydroxyphenyl boronate pinacol ester (124I-HPBPE) that we believe could be a first generation chemoselective imaging agent for the non-invasive in vivo delineation of H2O2 levels. Going forward, we plan to further explore the chemical reactivity of 124I-HPBPE, followed by subsequent in vitro and in vivo validation studies. In the end, while the synthesis of the prospective probe required more time and effort than we anticipated, we firmly believe that this research project could lead to the development of a clinically transformative imaging agent.


Descriptors :   *PROSTATE CANCER , *TOMOGRAPHY , BONDING , BORON , CELLS(BIOLOGY) , CHEMICAL REACTIONS , ESTERS , GROWTH(GENERAL) , HOMING , HYDROGEN PEROXIDE , HYPOTHESES , IMAGES , IN VITRO ANALYSIS , IN VIVO ANALYSIS , INSTABILITY , LINKAGES , METASTASIS , NEOPLASMS , PEROXIDES , PROBES , PROSTATE GLAND , RADIOACTIVITY , REACTIVITIES , SKILLS , STRATEGY , VALIDATION


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE