The use of radiopharmaceuticals for molecular imaging of biochemical and physiological processes in vivo has evolved into an important diagnostic tool in modern nuclear medicine and medical research. Positron emission tomography (PET) is currently the most sophisticated molecular imaging methodology, mainly due to the unrivalled high sensitivity which allows for the studying of biochemistry in vivo on the molecular level. The most frequently used radionuclides for PET have relatively short half-lives (e.g. 11C: 20.4 min; 18F: 109.8 min) which may limit both the synthesis procedures and the time frame of PET studies. Iodine-124 (124I, t1/2 = 4.2 d) is an alternative long-lived PET radionuclide attracting increasing interest for long term clinical and small animal PET studies. The present review gives a survey on the use of 124I as promising PET radionuclide for molecular imaging. The first part describes the production of 124I. The second part covers basic radiochemistry with 124I focused on the synthesis of 124I-labeled compounds for molecular imaging purposes. The review concludes with a summary and an outlook on the future prospective of using the long-lived positron emitter 124I in the field of organic PET chemistry and molecular imaging.

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Cyclin-dependent kinases 4 and 6 (Cdk4/6) are important components of cell cycle activation and control in early G(1) phase. Both enzymes and their regulators, e.g., cyclins, play critical roles in embryogenesis, homeostasis, and cancerogenesis. Cdk4/6 are attractive targets for cancer treatment. Recently, numerous selective small molecule inhibitors of Cdk4/6 have been developed. The potential of Cdk4/6 inhibitors, particularly, pyrido[2,3-d]pyrimidine derivatives, as both anti-cancer drugs and 124I- and 18F-radiolabeled tracers for cancer imaging using positron emission tomography is discussed.

The cyclin-dependent kinase (Cdk)-cyclin D/retinoblastoma (pRb)/E2F cascade, which controls the G1/S transition of cell cycle, has been found to be altered in many neoplasias. Inhibition of this pathway by using, for example, selective Cdk4 inhibitors has been suggested to be a promising approach for cancer therapy. We hypothesized that appropriately radiolabeled Cdk4 inhibitors are suitable probes for tumor imaging and may be helpful studying cell proliferation processes in vivo by positron emission tomography. Herein, we report the synthesis and biological, biochemical, and radiopharmacological characterizations of two 124I-labeled small molecule Cdk4 inhibitors (8-cyclopentyl-6-iodo-5-methyl-2-(4-piperazin-1-yl-phenylamino)-8H-pyrido[2,3-d]-pyrimidin-7-one (CKIA) and 8-cyclopentyl-6-iodo-5-methyl-2-(5-(piperazin-1-yl)-pyridin-2-yl-amino)-8H-pyrido[2,3-d]pyrimidin-7-one (CKIB)). Our data demonstrate a defined and specific inhibition of tumor cell proliferation through CKIA and CKIB by inhibition of the Cdk4/pRb/E2F pathway emphasizing potential therapeutic benefit of CKIA and CKIB. Furthermore, radiopharmacological properties of [124I]CKIA and [124I]CKIB observed in human tumor cells are promising prerequisites for in vivo biodistribution and imaging studies.

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