New nicotine-like imaging agent holds promise in PET studies, may help diagnose Alzheimer’s disease

The chemical nicotine–a main ingredient in tobacco–may hold promise in the early diagnosis of Alzheimer’s disease, give insight into therapeutic interventions for nicotine addiction and possibly complement the diagnosis of certain forms of lung cancer, according to a study in the January issue of the Society of Nuclear Medicine’s Journal of Nuclear Medicine.

Researchers are examining nicotine’s cognitive, behavioral and addictive actions, and, by looking at targets in the brain where nicotine acts, researchers hope to address several major health problems, said SNM member Jogeshwar Mukherjee, Ph.D., associate professor in residence at the department of psychiatry and human behavior, Brain Imaging Center, at the University of California at Irvine (UCI). A team of researchers from UCI and the Kettering Medical Center in Dayton, Ohio, found that imaging studies with a new fluorine-18 labeled imaging agent, nifrolidine, complement other ongoing positron emission tomography (PET) studies currently underway with nicotine-like PET imaging agents.

Nifrolidine was developed to specifically bind to a receptor (protein) that is present in the human and nonhuman brain; this receptor is involved in several brain functions, particularly cognition and certain aspects of learning and memory, according to Mukherjee. By binding at the same place as nicotine, nifrolidine helps to measure how and where nicotine acts. PET studies can be performed with nifrolidine to provide information on the receptor present in various regions of the brain. “Research has shown that with Alzheimer’s disease there is a gradual loss of these receptors; therefore, there is a potential of early diagnostic value in nifrolidine-PET imaging,” he said.

In addition, nicotine addiction and lung cancer may be linked to this receptor. The availability of a good PET imaging agent for this receptor will allow preclinical and clinical studies, leading to better understanding of different medical conditions and eventually helping in their diagnosis and treatment, said Mukherjee.

Additional research and work with animal subjects must be completed before this tracer can be used to demonstrate applications in human studies, said the co-author of “Synthesis and Evaluation of Nicotine á4â2 Receptor Radioligand, 5-(3’-18F-Fluoropropyl)-3-(2-(S)- Pyrrolidinylmethoxy) Pyridine, in Rodents and PET in Nonhuman Primate.” The team plans to obtain complete toxicity and dosimetry data in order to obtain approval for conducting human studies.

“Synthesis and Evaluation of Nicotine á4â2 Receptor Radioligand, 5-(3’-18F-Fluoropropyl)-3-(2-(S)- Pyrrolidinylmethoxy) Pyridine, in Rodents and PET in Nonhuman Primate” was written by Sankha Chattopadhyay, Ph.D., Baogang Xue, M.D., Daphne Collins, B.E., and Rama Pichika, Ph.D., all at the department of psychiatry and human behavior, Brain Imaging Center, University of California, Irvine, Calif.; Rudy Bagnera, B.S., and Frances M. Leslie, Ph.D., both at the department of pharmacology, University of California, Irvine, Calif.; Bradley T. Christian, Ph.D., Bingzhi Shi, Ph.D., and Tanjore K. Narayanan, Ph.D., all at the department of PET/nuclear medicine, Kettering Medical Center, Dayton, Ohio; and Steven G. Potkin, M.D., and Jogeshwar Mukherjee, Ph.D., both at the department of psychiatry and human behavior, Brain Imaging Center, University of California, Irvine, Calif.