Abstract
Positron emission tomography (PET) offers the study of biochemical,
physiological, and pharmacological functions at a cellular and molecular level.
The performance of a PET study mostly depends on the used radiotracer of
interest. However, the development of a novel PET tracer is very difficult, as
it is required to fulfill a lot of important criteria. PET radiotracers usually
encounter different chemical modifications including redox reaction, hydrolysis,
decarboxylation, and various conjugation processes within living organisms. Due
to this biotransformation, different chemical entities are produced, and the
amount of the parent radiotracer is declined. Consequently, the signal measured
by the PET scanner indicates the entire amount of radioactivity deposited in the
tissue; however, it does not offer any indication about the chemical disposition
of the parent radiotracer itself. From a radiopharmaceutical perspective, it is
necessary to quantify the parent radiotracer’s fraction present in the tissue.
Hence, the identification of radiometabolites of the radiotracers is vital for
PET imaging. There are mainly two reasons for the chemical identification of PET
radiometabolites: firstly, to determine the amount of parent radiotracers in
plasma, and secondly, to rule out (if a radiometabolite enters the brain) or
correct any radiometabolite accumulation in peripheral tissue. Besides,
radiometabolite formations of the tracer might be of concern for the PET study,
as the radiometabolic products may display considerably contrasting distribution
patterns inside the body when compared with the radiotracer itself. Therefore,
necessary information is needed about these biochemical transformations to
understand the distribution of radioactivity throughout the body. Various
published review articles on PET radiometabolites mainly focus on the sample
preparation techniques and recently available technology to improve the
radiometabolite analysis process. This article essentially summarizes the
chemical and structural identity of the radiometabolites of various radiotracers
including [11C]PBB3,
[11C]flumazenil,
[18F]FEPE2I, [11C]PBR28,
[11C]MADAM, and
(+)[18F]flubatine. Besides, the importance of
radiometabolite analysis in PET imaging is also briefly summarized. Moreover,
this review also highlights how a slight chemical modification could reduce the
formation of radiometabolites, which could interfere with the results of PET
imaging.
Graphical abstract
Design and Synthesis of Curcumin Analogues for in Vivo Fluorescence Imaging and Inhibiting Copper-Induced Cross-Linking of Amyloid Beta Species in Alzheimer’s Disease