Application of a small molecule radiopharmaceutical concept to improve kinetics

Recently, large molecules or nanoparticles are actively studied as radiopharmaceuticals. However, their kinetics is problematic because of a slow penetration through the capillaries and slow distribution to the target. To improve the kinetics, a two-step targeting method can be applied by using small molecules and very rapid copper-free click reaction. Although this method might have limitations such as internalization of the first targeted conjugate, it will provide high target-to-non-target ratio imaging of radiopharmaceuticals. The majority of radiopharmaceuticals belong to small molecules of which the molecular weight is less than 2000 Da, and the molecular size is smaller than 2 nm generally. The outstanding feature of the small molecule radiopharmaceuticals compared to large molecules is with their kinetics. Their distribution to target and clearance from non-target tissues are very rapid, which is the essential requirement of radiopharmaceuticals. In conclusion, the small molecule radiopharmaceuticals generally show excellent biodistribution properties; however, they show poor efficiency of radioisotope delivery. Large molecule or nanoparticle radiopharmaceuticals have advantages of multimodal and efficient delivery, but lower target-to-non-target ratio. Two-step targeting using a bio-orthogonal copper-free click reaction can be a solution of the problem of large molecule or nanoparticle radiopharmaceuticals. The majority of radiopharmaceuticals belong to small molecules of which the molecular weight is less than 2000 Da, and the molecular size is smaller than 2 nm generally. The outstanding feature of the small molecule radiopharmaceuticals compared to large molecules is with their kinetics. Their distribution to target and clearance from non-target tissues are very rapid, which is the essential requirement of radiopharmaceuticals