Prostate to different biologically relevant linker groups and

Prostate
cancer remains a major health-related problem and yet there is no effective
option available for the treatment of advanced metastatic prostate cancer. Thus,
there is a high clinical need for the development of new and effective tumor
targeting agents together with more effective treatment modalities that could
improve the patient outcome. Prostate specific membrane antigen (PSMA) is highly expressed in all stages of prostate cancer making PSMA a
potential molecular target for detecting metastatic prostate cancer. The
development of PSMA binding agents, radiolabeled with diagnostic and/or
therapeutic radionuclides, holds great clinical potential for a new era of
personalized management of metastatic prostate cancer in the Kingdom.

       In this project, we propose the
synthesis and biological evaluation of several PSMA-specific tumor targeting
agents, derived from the “glutamate-urea-lysine” pharmacophore (essential
for PSMA receptor recognition), conjugated to different biologically relevant
linker groups and radiometal chelating agents. After radiolabeling with PET and
SPECT based diagnostic radionuclides (68Ga and 99mTc),
these PSMA targeting agents will be investigated for the initial diagnosis
of prostate cancer in vivo. Furthermore, the same 68Ga-labeled PSMA targeting
agents will be radiolabeled with a low-energy ?-emitter, 177Lu, to formulate
theranostic radiopharmaceuticals in order to facilitate radionuclide therapy and
monitoring disease progression and therapeutic response. The outcome of this
project may provide the development of potent PSMA-specific
radiopharmaceuticals for early and precise detection of prostate cancer and
eventually translate these findings into the clinical settings. From these
preclinical evaluation studies, the lead PSMA-specific compound with favorable
properties will be selected for further evaluation in clinical trials.

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