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, t_1/2 = 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.

Purpose: To optimize the direct production of⁶⁸Ga on a cyclotron, via the⁶⁸Zn(p,n)⁶⁸Ga reaction using a liquid cyclotron target. We Investigated the yield of cyclotron-produced⁶⁸Ga, extraction of [⁶⁸Ga]GaCl₃and subsequent [⁶⁸Ga]Ga-PSMA-11 labeling using an automated synthesis module.Methods: Irradiations of a 1.0 M solution of [⁶⁸Zn]Zn(NO₃)₂in dilute (0.2–0.3 M) HNO₃were conducted using GE PETtrace cyclotrons and GE⁶⁸Ga liquid targets. The proton beam energy was degraded to a nominal 14.3 MeV to minimize the co-production of⁶⁷Ga through the⁶⁸Zn(p,2n)⁶⁷Ga reaction without unduly compromising⁶⁸Ga yields. We also evaluated the effects of varying beam times (50–75 min) and beam currents (27–40 μA). Crude⁶⁸Ga production was measured. The extraction of [⁶⁸Ga]GaCl₃was performed using a 2 column solid phase method on the GE FASTlab Developer platform. Extracted [⁶⁸Ga]GaCl₃was used to label [⁶⁸Ga]Ga-PSMA-11 that was intended for clinical use.Results: The decay corrected yield of⁶⁸Ga at EOB was typically > 3.7 GBq (100 mCi) for a 60 min beam, with irradiations of [⁶⁸Zn]Zn(NO₃)₂at 0.3 M HNO_3.Target/chemistry performance was more consistent when compared with 0.2 M HNO₃. Radionuclidic purity of⁶⁸Ga was typically > 99.8% at EOB and met the requirements specified in the European Pharmacopoeia (< 2% combined^66/67Ga) for a practical clinical product shelf-life. The activity yield of [⁶⁸Ga]GaCl₃was typically > 50% (~ 1.85 GBq, 50 mCi); yields improved as processes were optimized. Labeling yields for [⁶⁸Ga]Ga-PSMA-11 were near quantitative (~ 1.67 GBq, 45 mCi) at EOS. Cyclotron produced [⁶⁸Ga]Ga-PSMA-11 underwent full quality control, stability and sterility testing, and was implemented for human use at the University of Michigan as an Investigational New Drug through the US FDA and also at the Royal Prince Alfred Hospital (RPA).Conclusion: Direct cyclotron irradiation of a liquid target provides clinically relevant quantities of [⁶⁸Ga]Ga-PSMA-11 and is a viable alternative to traditional⁶⁸Ge/⁶⁸Ga generators.