The studies described in this research proposal involve the design and preparation of novel 99mTc chelates linked to a piperidine pharmacophore. Such radioligands would be expected to exhibit potential for the diagnosis and management of neurological dysfunctions in monoamine systems. As such they will provide the ability to improve state of human health care by affording single photon computed tomography (SPECT) agents for diagnosis and management of Parkinson's disease, chelates linked to our novel piperidine pharmacophore. The piperidine pharmacophore can be SPECT agents for the dopamine transporter, but also the serotonin and norepinephrine transporters. The ligands prepared will initially be labeled as rhenium(oxo) species as a non-radioactive model for 99mTc. The in vitro activity at the monoamine transporters will be determined and compounds found to exhibit high binding affinity and selectivity for the monoamine transporters will be radiolabeled with 99mTc.
As no SPECT agents are currently available for the diagnosis and management of diseases involving dysfunctions in monoaminergic neurotransmission, such as Parkinson's disease, ADD/ADHD and depression. The successful completion of this proposal will ultimately lead to the development and marketing of 99mTc based SPECT agents for the diagnosis and management of such diseases.
