## 3 Discussion  
The works discussed in this article focused on the search for a diagnostic radiopharmaceutical for the earliest possible diagnosis of Alzheimer's disease. The biologically active molecule in these radiopharmaceuticals was the medicinal preparation tacrine (or its derivatives) that was approved by the FDA in 1993 for the treatment of Alzheimer's disease and was, in 2013, withdrawn due to harmful side effects. However, since radiopharmaceuticals are administered to the patient in microgram quantities and, in the case of diagnostic radiopharmaceuticals, their use is not frequent, the problem of the harmfulness of tacrine is not significant. However, due to the high ability of tacrine to cross the blood-brain barrier, its use as a vector in radiopharmaceuticals is justified. As can be observed from the presented works, radiotracers based on the tacrine molecule, in which the radionuclide (\({}^{3}\)H, \({}^{11}\)C, \({}^{14}\)C) is an isotope of one of the elements included in the tacrine molecule [9; 10; 11; 12], easily cross the blood-brain barrier and accumulate in significant amounts in the brain. However, such radiopreparations are not easily available due to the too complicated procedures for synthesizing these radiopreparations, which are difficult or even impossible to perform in clinical conditions (in hospital laboratories). The procedures for obtaining radioconjugates in the form of a tacrine solution, tacrine microemulsion and tacrine mucoadhesive microemulsion labeled (directly) with \({}^{99\text{m}}\)Tc and identifying them using the radio-TLC method [24; 25] are relatively easy and can be performed in hospital laboratories. These radiopreparations accumulated relatively well in the brain, but regarding these compounds, there is no knowledge about their composition and structure, which, according to the authors of this review article, is a significant disadvantage. For these radiopreparations, intranasal administration has proven to be more effective than intravenous administration. Radiopreparations based on a relatively minimally changed tacrine molecule also accumulated satisfactorily in the brain [26; 27; 28; 29; 30]. Modification of tacrine by adding a methyl group, fluorine or iodine did not reduce the ability of tacrine to cross the blood-brain barrier. The most convenient procedure for the synthesis of diagnostic radiopharmaceuticals in clinical conditions is to perform a labeling reaction with generator radionuclides (\({}^{99\text{m}}\)Tc, \({}^{68}\)Ga) of the active substance (tacrine or its derivative, often previously coupled with an appropriate chelator) included in the so-called kit [33; 34; 35; 36] (kits are ready-made sets containing, in lyophilized form, the appropriate reagents in the appropriate quantities needed for the synthesis of a given radiopharmaceutical). However, the use of chelators significantly changes both the size of the final radiopreparation and its lipophilicity. Changes in these parameters do not have a significant impact on the inhibitory properties towards acetyl- and butylcholinesteraseterase, but their effect in vivo is a significant reduction in the ability of the radiopharmaceutical to cross the blood-brain barrier and accumulate in the brain in the amounts necessary for imaging. To sum up, it can be said that, despite many works, it has not been possible to find a radiopreparation based on tacrine or its derivatives that meets the requirements for radiopharmaceuticals. Perhaps it would be advisable to search for another biological molecule involved in the course of [PERSON]'s disease from its earliest stage. Conceptualization, E.G. and P.K. ; writing--original draft preparation, E.G. and P.K. ; writing--review and editing, E.G. and P.K. ; visualization, E.G. and P.K. ; supervision, E.G. ; project administration, E.G. and P.K. All authors have read and agreed to the published version of the manuscript. This research received no external funding.