Recent Developments in PET and SPECT Radiotracers as Radiopharmaceuticals for Hypoxia Tumors

Abstract

Hypoxia, a deficiency in the levels of oxygen, is a common feature of most solid tumors and induces many characteristics of cancer. Hypoxia is associated with metastases and strong resistance to radio- and chemotherapy, and can decrease the accuracy of cancer prognosis. Non-invasive imaging methods such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) using hypoxia-targeting radiopharmaceuticals have been used for the detection and therapy of tumor hypoxia. Nitroimidazoles are bioreducible moieties that can be selectively reduced under hypoxic conditions covalently bind to intracellular macromolecules, and are trapped within hypoxic cells and tissues. Recently, there has been a strong motivation to develop PET and SPECT radiotracers as radiopharmaceuticals containing nitroimidazole moieties for the visualization and treatment of hypoxic tumors. In this review, we summarize the development of some novel PET and SPECT radiotracers as radiopharmaceuticals containing nitroimidazoles, as well as their physicochemical properties, in vitro cellular uptake values, in vivo biodistribution, and PET/SPECT imaging results.

Synthesis and Preclinical Evaluation of Two Novel 68Ga-Labeled Bispecific PSMA/FAP-Targeted Tracers with 2-Nal-Containing PSMA-Targeted Pharmacophore and Pyridine-Based FAP-Targeted Pharmacophore

“…vious findings that more hydrophilic radiotracers will have faster pharmacokinetics and clearance and, hence, a better tumor-to-background contrast ratio [35]. In addition, there are no significant differences in the tumor uptake or the tumor-to-background contrast ratios between [ 68 Ga]Ga-AV01084 and [ 68 Ga]Ga-AV01088, which indicates that the position of the DOTA chelator at the lysine linker does not have a crucial effect on the pharmacokinetics of the tracers.…”

Polymeric Nanoparticles for Drug Delivery

“…986,987 Consequently, SPECT and PET are not only valuable in monitoring drug metabolism but also play a crucial role in the diagnosis and staging of cancer. 988 A variety of radionuclides are utilized in clinical applications. For SPECT, these include technetium-99m (half-life = 6 h), indium-111 (half-life = 67.2 h), and iodine-123 (half-life = 13.2 h).…”

“…Furthermore, in clinical settings, SPECT and PET can be integrated with anatomic imaging methods, such as computed X-ray tomography (CT), to develop hybrid systems like SPECT/CT and PET/CT. These combinations are instrumental in generating three-dimensional images, enabling precise localization. , Consequently, SPECT and PET are not only valuable in monitoring drug metabolism but also play a crucial role in the diagnosis and staging of cancer . A variety of radionuclides are utilized in clinical applications.…”

18F-Fluorination of Nitroimidazolyl-Containing Sultone: A Direct Access to a Highly Hydrophilic Radiotracer for High-Performance Positron Emission Tomography Imaging of Hypoxia

“…Hypoxia is an important hallmark of solid tumors and plays a critical role in various cellular and physiologic processes, including cell proliferation, angiogenesis, tumor invasion, and metastasis. , It has also been shown to contribute to chemo- and radiotherapy resistance associated with poor clinical prognosis . It is well recognized that knowledge of the location, extent, and reduction of hypoxia can provide valuable information for adapting treatments and potentially improving therapeutic outcomes, especially in radiotherapy and dose-painting approaches. − For many years, positron emission tomography (PET) has proven to be a suitable noninvasive in vivo imaging technique for detecting hypoxic tumor regions. , Hypoxia clinical PET imaging is mainly based on the use of 2-nitroimidazole containing radiopharmaceuticals, e.g., 18 F-labeled fluoromisonidazole ([ 18 F]FMISO) that remains the reference radiotracer for this purpose due to its well-establised prognostic potential. ,− Nitroimidazolyl radiotracers have been shown to penetrate cells by passive diffusion and then undergo a two-step reduction process, with the first step being reversible when oxygen is present. Thus, the radiotracers stand out unchanged from normal cells, whereas they become irreversibly trapped in hypoxic cells due to the in situ conjugation of their reduced forms with enzymes and proteins.…”