PET Radiopharmaceuticals for Personalized Medicine

Recent advances in the self-shielded cyclotrons, improved targets, video-monitored hot cells design, and automated PET radiopharmaceutical (RPs) synthesis modules, utilizing computer-controlled graphic user interphase (GUI) has revolutionized PET molecular imaging technology for basic biomedical research and theranostics to accomplish the ultimate goal of evidence-based personalized medicine. Particularly, [F-18]HX4: (3-[F-18]fluoro-2-(4-((2-nitro-1Himidazol-1-yl) methyl)-1H-1,2,3,-triazol-1-yl)-propan-1-ol), F-18-FAZA: 1-(5-[F-18]Fluoro-5-deoxy-alpha-D-arabinofuranosyl)-2nitroimidazole, and F-18-FMSIO: F-18-Ffluoromisonidazole to assess tumor hypoxia, [F-18] FB-VAD-FMK: [F-18] 4-fluorobenzylcarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone to determine in vivo apoptosis, Cu-64-PTSM: Cu-64-Pyrualdehyde Bis-N-Methylthiosemicarbazone for brain and myocardial perfusion imaging, and Ga-68-DOTATOC: (68)GaDOTAD- Phy(1)-Tyr(3)-octreotide and Ga-68-DOTANOC: Ga-68-(1,4,7,10-tetraazacyclododecaneN, N', N '', N '''-tetraacetic acid)-1-NaI3-octreotide for neuroendocrine and neural crest tumors have demonstrated great promise in personalized theranostics. Furthermore, multimodality imaging with I-124-PET/CT and (18)FDG-PET/CT rationalizes I-131 treatment in thyroid cancer patients to prevent cost and morbid toxicity. In addition to F-18-labeled PET-RPs used in clinical practice, novel discoveries of chemical reactions including transition metal-mediated cross-coupling of carbon-carbon, carbon-heterocarbon, and click chemistry at ambient temperature with significantly reduced synthesis times, labeled even with short-lived radionuclides such as C-11, has facilitated development of novel PET-RPs. These innovative approaches to synthesize PET-RPs and efficient image acquisition capabilities have improved the resolution of multimodality imaging and significantly reduced the radiation exposure to patients as well as healthcare professionals. Future developments in novel PET-RPs, utilizing automated microfluidic synthesis modules and multifunctional nanoparticles, will improve biomarker discovery, internal dosimetry, pharmacokinetics, immunotherapy, and stem cell tracking in regenerative medicine. This review provides recent developments in the synthesis of clinically-significant cyclotron and generator-based PET-RPs with potential applications in cardiovascular diseases, neurodegenerative diseases, and cancer to accomplish the ultimate goal of evidence-based personalized theranostics.