Perspectives of Methotrexate-Based Radioagents for Application in Nuclear Medicine

Abstract

Methotrexate is a gold standard among disease modifying antirheumatic drugs and is also extensively used clinically in combination with oncological therapies. Thus, it is not surprising that nuclear medicine found an interest in methotrexate in the search for diagnostic and therapeutic solutions. Numerous folate-related radiopharmaceuticals have been proposed for nuclear medicine purposes; however, methotrexate radioagents represent only a minority. This imbalance results from the fact that methotrexate has significantly weaker affinity for folate receptors than folic acid. Nevertheless, radiolabeled methotrexate agents utilized as a tool for early detection and imaging of inflammation in rheumatoid arthritis patients gave promising results. Similarly, the use of multimodal MTX-release nanosystems may find potential applications in radiosynovectomy and theranostic approaches in folate receptor positive cancers.

NIR-Responsive Methotrexate-Modified Iron Selenide Nanorods for Synergistic Magnetic Hyperthermic, Photothermal, and Chemodynamic Therapy

“…After crossing the cell membrane, MTX undergoes rapid intracellular bioconversion to a polyglutamate derivative via folyl polyglutamyl synthase. This bioactivation considerably increases the pharmacological action of MTX by prolonging its intracellular retention and increasing its inhibitory activity, thereby inhibiting the cellular synthesis of DNA and RNA building blocks and inducing cell apoptosis . MTX is used in dual-role compounds that can function as both tumor-targeted binding sites and therapeutic drugs.…”

Therapeutic Potential of Methotrexate-Loaded Superparamagnetic Iron Oxide Nanoparticles Coated with Poly(lactic-co-glycolic acid) and Polyethylene Glycol against Breast Cancer: Development, Characterization, and Comprehensive In Vitro Investigation

“…Apart from its original use as a cancer chemotherapeutic agent, it has been suggested for several other diseases, such as psoriasis, multiple sclerosis, Crohn’s disease, and rheumatoid arthritis. Methotrexate acts as a cancer chemotherapeutics agent by inhibiting dihydrofolate reducatase with high affinity, resulting in the depletion of tetrahydrofolates required for the synthesis of purines and thymidylate . Subsequently, the synthesis of DNA and RNA, as well as other metabolic reactions, are interrupted; however, MTX does not act simply as an antiproliferating agent for the cells responsible for the joint inflammations in rheumatoid arthritis .…”

Synthesis of 2‐Perfluoroalkylazuleno[2,1‐d]pyrimidin‐4(3H)‐ones via Brønsted Acid‐Mediated Intramolecular Cyclization and Transformation into Pyrimidines

“…[1] Pyrimidine and pyrimidinone derivatives are compounds with a range of pharmaceutical uses. [2] A number of drugs have been developed based on them, such as methotrexate (anticancer agent), [3] trimethoprim (antibiotic), [4] lamivudine (antiretroviral agent), [5] acyclovir (antiviral agent), [6] azathioprine (immunosuppressive agent), [7] and so on. As mentioned above, incorporation of trifluoromethyl or perfluoroalkyl groups into pyrimidine and pyrimidinone derivatives can alter their physical and chemical characteristics of the molecules, resulting in improved stability and degradation resistance, pharmacokinetic properties, and therapeutic efficacy, which can increase the suitability of these derivatives for use as pharmaceuticals.…”