Radiochemistry, Production Processes, Labeling Methods, and ImmunoPET Imaging Pharmaceuticals of Iodine-124

Target-specific biomolecules, monoclonal antibodies (mAb), proteins, and protein fragments are known to have high specificity and affinity for receptors associated with tumors and other pathological conditions. However, the large biomolecules have relatively intermediate to long circulation half-lives (>day) and tumor localization times. Combining superior target specificity of mAbs and high sensitivity and resolution of the PET (Positron Emission Tomography) imaging technique has created a paradigm-shifting imaging modality, ImmunoPET. In addition to metallic PET radionuclides, (124)I is an attractive radionuclide for radiolabeling of mAbs as potential immunoPET imaging pharmaceuticals due to its physical properties (decay characteristics and half-life), easy and routine production by cyclotrons, and well-established methodologies for radioiodination. The objective of this report is to provide a comprehensive review of the physical properties of iodine and iodine radionuclides, production processes of (124)I, various (124)I-labeling methodologies for large biomolecules, mAbs, and the development of (124)I-labeled immunoPET imaging pharmaceuticals for various cancer targets in preclinical and clinical environments. A summary of several production processes, including (123)Te(d,n)(124)I, (124)Te(d,2n)(124)I, (121)Sb(α,n)(124)I, (123)Sb(α,3n)(124)I, (123)Sb((3)He,2n)(124)I, (nat)Sb(α, xn)(124)I, (nat)Sb((3)He,n)(124)I reactions, a detailed overview of the (124)Te(p,n)(124)I reaction (including target selection, preparation, processing, and recovery of (124)I), and a fully automated process that can be scaled up for GMP (Good Manufacturing Practices) production of large quantities of (124)I is provided. Direct, using inorganic and organic oxidizing agents and enzyme catalysis, and indirect, using prosthetic groups, (124)I-labeling techniques have been discussed. Significant research has been conducted, in more than the last two decades, in the development of (124)I-labeled immunoPET imaging pharmaceuticals for target-specific cancer detection. Details of preclinical and clinical evaluations of the potential (124)I-labeled immunoPET imaging pharmaceuticals are described here.