68ga-dotanoc and Neoplasms

Recent advances in the self-shielded cyclotrons, improved targets, videomonitored 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, [18F]HX4: (3-[18F]fluoro-2-(4-((2-nitro-1Himidazol-1-yl)methyl)-1H-1,2,3,-triazol-1- yl)-propan-1-ol), 18F-FAZA: 1-(5-[18F]Fluoro-5-deoxy-α-D-arabinofuranosyl)-2- nitroimidazole, and 18F-FMSIO: 18F-Ffluoromisonidazole to assess tumor hypoxia, [18F]FB-VAD-FMK: [18F]4-fluorobenzylcarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone to determine in vivo apoptosis, 64Cu-PTSM: 64Cu-Pyrualdehyde Bis-NMethylthiosemicarbazone for brain and myocardial perfusion imaging, and 68Ga-DOTATOC: 68Ga- DOTAD-Phy1-Tyr3-octreotide and 68Ga-DOTANOC: 68Ga-(1,4,7,10-tetraazacyclododecane- N,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 124IPET/ CT and 18FDG-PET/CT rationalizes 131I treatment in thyroid cancer patients to prevent cost and morbid toxicity. In addition to 18F-labeled PET-RPs used in clinical practice, novel discoveries of chemical reactions including transition metal-mediated cross-coupling of carbon-carbon, carbonheterocarbon, and click chemistry at ambient temperature with significantly reduced synthesis times, labeled even with short-lived radionuclides such as 11C, 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.

Topics: Cardiovascular Diseases; Evidence-Based Medicine; Humans; Microfluidics; Multimodal Imaging; Neoplasms; Neurodegenerative Diseases; Organometallic Compounds; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Precision Medicine; Radiopharmaceuticals

68Ga-DOTA-SSTRTs PET/CT has become the most promising noninvasive procedure to study well-differentiated NET. Although the excellent diagnostic accuracy of the procedure is well known, its use is limited to specialized centers in Europe as parts of clinical trials. Literature reports confirm the superiority of 68Ga-DOTA-SSTRTs PET/CT for the assessment of well-differentiated NET over morphologic imaging procedures, SRS, and even PET/CT using metabolic radiotracers. 68Ga-DOTA-SSTRTs provide good visualization of NET lesions at both the primary and the metastatic sites (node, bone, liver, and unusual localizations). The advantages of their use over metabolic tracers (18F-DOPA, 18F-FDG) are not only limited to a better overall detection rate but also to the fact that they also provide data on SSTR expression on target lesions, resulting a fundamental procedure before starting therapy with either hot or cold somatostatin analogues. Moreover, they can be used also in centers without an on-site cyclotron. To interpret 68Ga-DOTA-SSTRTs images correctly, it is crucial to understand the tracer’s biodistribution as well as the conditions that may alter tracer uptake. Considering that SSTR are expressed on activated lymphocytes, all areas of inflammation show 68Ga-DOTA-SSTRTs uptake. Areas of increased uptake in frequent sites of inflammation (eg, thyroid, mediastinal nodes, inguinal nodes, and nodes adjacent to areas of recent surgery/trauma) should be interpreted with care. A detailed clinical history with particular attention to concomitant disorders (eg, sarcoidosis, chronic gastritis, chronic thryoiditis) and recent invasive procedures or trauma may often help image interpretation. The presence of uptake in the head of the pancreas should always be carefully evaluated because it may often be benign. Otherwise, because the pancreas is also a frequent site of NET onset, particular attention should be devoted to the evaluation of the uptake pattern (diffuse more likely to be benign) and to the comparison with other imaging techniques.

Topics: Diagnosis, Differential; Gallium Radioisotopes; Humans; Neoplasms; Octreotide; Organometallic Compounds; Positron-Emission Tomography; Radiopharmaceuticals; Receptors, Somatostatin; Tissue Distribution; Tomography, X-Ray Computed

Topics: Acetates; Carbon Radioisotopes; Choline; Fluorodeoxyglucose F18; Gallium Radioisotopes; Humans; Medical Oncology; Methionine; Neoplasms; Organometallic Compounds; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity