###### Abstract  
From 1993 to 2013, tacrine was an approved drug for Alzheimer's disease. Due to its strong inhibitory properties towards cholinesterase, tacrine causes an increase in the level of the neurotransmitter acetylcholine in the cholinergic system of the central nervous system. This work presents a review of articles in which tacrine or its derivatives labeled with the radionuclides \({}^{3}\)H, \({}^{11}\)C, \({}^{14}\)C, \({}^{123}\)I, \({}^{99}\)Tc and \({}^{68}\)Ga were used as vectors in radiotracers dedicated to the diagnosis of Alzheimer's disease. The possibility of clinical applications of the obtained radiopreparations was assessed by analyzing their physicochemical properties, ability to cross the blood-brain barrier and the level of uptake in the brain. Based on these data, it was shown that radiopreparations based on the tacrine molecule or its very close analogues retain the ability to cross the blood-brain barrier, while radiopreparations containing a more modified tacrine molecule (connected via a linker to a radionuclide chelator) lose this ability. This is probably the result of the addition of a chelator, which significantly increases the size of the radiopreparation and reduces its lipophilicity. Computer docking studies of tacrine derivatives and/or radiopreparations showed how these compounds bind to the active sites of acetyl- and butyrylcholinesteraseerase. Alzheimer's disease; tacrine; radiopharmaceuticals; molecular modeling; PET; SPECT +
Footnote †: journal: Medical Imaging  
**Citation**: [PERSON]; [PERSON] [PERSON] Design, Synthesis and Molecular Modeling Study of Radiotracers Based on Tacrine and Its Derivatives for Study on Alzheimer's Disease and Its Early Diagnosis. loss of memory and cognitive function, caused by a deficiency of the neurotransmitter acetylcholine (ACh). ACh deficiency results from its hydrolysis, induced by the enzyme acetylcholinesterase (AChE), and leads to the selective loss of cholinergic neurons in the cerebral cortex, basal ganglia and hippocampus [7]. The two main therapeutic strategies in AD are influencing the processing of amyloid precursor protein (APP) and slowing the decline of neuronal degeneration and improving cholinergic neurotransmission [1; 7; 8; 9; 10]. As therapeutic agents in the mild and moderate stages of Alzheimer's disease, AChE inhibitors, e.g., tacrine, rivastigmine, galantamine and donepezil, have been used [11; 12; 13; 14]. One of the known and tested inhibitors is tacrine (1,2,3,4-tetrahydro-9-amino acridine, THA)--the active substance of the drug Cognex [15; 16], approved in 1993 by the US Food and Drug Administration (FDA) for use in treating the symptoms of AD. The therapeutic effect of THA is achieved by reversible binding to AChE and its inactivation, which results in an increase in the concentration of ACh at cholinergic synapses, thanks to which a greater number of cholinergic neurons remain intact, and the progression of the disease is slowed down [10; 12; 17; 18]. Tacrine is characterized by high biological activity towards AChE, but unfortunately, it causes a number of common side effects (nausea, indigestion, vomiting, anorexia, abdominal pain, diarrhea, skin rash) and a high risk of liver damage, especially when using large doses of the drug [11; 12; 13; 14; 19]. In 2013, it was withdrawn due to hepatotoxicity and cardiovascular problems occurring in patients. Nevertheless, both tacrine and its derivatives have been used as biologically active molecules in potential radiopharmaceuticals dedicated to the early diagnosis of Alzheimer's disease [1]. Diagnostic radiopharmaceuticals are compounds that use a biologically active molecule as a vector and contain a diagnostic radionuclide emitting gamma or beta plus radiation. They are administered to the patient in nanomolar amounts, so they do not cause any morphological changes in the body. At the same time, registration of the emitted radiation allows for the precise location of the radiopharmaceutical in the patient's body and thus the location of the disease lesion.