Click-chemistry reactions in radiopharmaceutical chemistry: fast & easy introduction of radiolabels into biomolecules for in vivo imaging.
Today the term "click chemistry" is often used equivalent with the copper-catalyzed 1,3-dipolar Huisgen cycloaddition. Originally, the concept was introduced in 2001 to describe reactions fulfilling a set of criteria that are most useful for chemical syntheses in drug research. In radiopharmaceutical chemistry where short lived radioisotopes are introduced into various different substance classes for in vivo imaging of biochemical processes, the expanding field of radioactive bioconjugation has become predominant. Labeled biomolecules such as peptides, proteins and oligonucleotides generated via bioconjugation of chelators for radiometal introduction as well as novel valuable secondary precursors for (18)F labeling have enriched the growing field of molecular imaging substantially. When introducing radioactive nuclides with a very short half-life into biomolecules, some of the typical criteria defined by click-chemistry are more crucial than others. Time is always the most important issue, whereas avoiding the formation of by-products that have to be removed without chromatography is of minor importance. The short-lived radionuclide (11)C for example has a physical half-life of only 20 min so that the labeling procedure cannot exceed 40-60 minutes (2-3 half-lifes). In this contribution, we outline reactions and molecules which meet the requirements of click chemistry reactions and are suitable for radiosyntheses of short lived SPECT ((99m)Tc: t(1/2) = 6 h, (111)In: t(1/2) = 2.81 d) and PET ((11)C: t(1/2) = 20.3 min to (64)Cu: t(1/2) = 12.7 h) radiotracers for in vivo imaging of biological processes and review the contributions in the field of radiochemical "click-reactions" - 1,3-dipolar Huisgen cycloadditions and beyond.
Wängler
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Lady Davis Institute for Medical Research, Jewish General Hospital, 3755, Chemin de la Côte-Ste-Catherine, Montreal, H3T 1E2, Québec, Canada. Carmen.Waengler@mail.mcgill.ca
Schirrmacher
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Bartenstein
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P
Wängler
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B
D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D006801:Humans; D017953:Isocyanates / Q000138:chemical synthesis / Q000737:chemistry; D007553:Isotope Labeling; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry; D014055:Tomography, Emission-Computed
D000588:Amines; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D017953:Isocyanates; D017319:Photosensitizing Agents; D019275:Radiopharmaceuticals; D013438:Sulfhydryl Compounds