Applications of nucleoside-based molecular probes for the in vivo assessment of tumour biochemistry using positron emission tomography (PET)

Abstract

Positron emission tomography (PET) is a non-invasive nuclear imaging technique. In PET, radiolabelled molecules decay by positron emission. The gamma rays resulting from positron annihilation are detected in coincidence and mapped to produce three dimensional images of radiotracer distribution in the body. Molecular imaging with PET refers to the use of positron-emitting biomolecules that are highly specific substrates for target enzymes, transport proteins or receptor proteins. Molecular imaging with PET produces spatial and temporal maps of the targetrelated processes. Molecular imaging is an important analytical tool in diagnostic medical imaging, therapy monitoring and the development of new drugs. Molecular imaging has its roots in molecular biology

Synthesis and Biologic Study of IV-14, a New Ribonucleoside Radiotracer for Tumor Visualization

“…We observed a significant (2.69 6 0.07 percentage injected dose) accumulation of radioactivity in HL60 cells with moderate UCK2 expression but with a high hENT 1 level after 24 h of incubation. The significance of hENT 1 for intracellular transport of IV-14 was supported in the case of HL60 cells by a strong inhibition of cellular uptake with p-nitrobenzylmercaptopurine, a known inhibitor of hENT 1 . However, the only moderate inhibition of cellular uptake of IV-14 with p-nitrobenzylmercaptopurine observed for MiaPaCa-2 cells suggests possible alternative mechanisms for the intracellular transport of IV-14 in different cell lines.…”

“…Numerous 29-deoxyribonucleosides have been studied for imaging and radiotherapy of tumors in preclinical and clinical models (1)(2)(3)(4). One of them, 39-deoxy-39-fluorothymidine (5), is already used in patients as a proliferation marker.…”

18Oxygen Substituted Nucleosides Combined with Proton Beam Therapy: Therapeutic Transmutation In Vitro

“…Examples include 18 F, which is inserted onto 2-deoxy-glucose (2-deoxy-2[ 18 F]-fluoroglucose) or onto the ribose of thymidine (3′-deoxy-3′- 18 F-fluorothymidine), where they provide valuable anatomic and cell proliferation information in cancer patients [ 6 , 7 ]. A means of producing targeted fluorine in a cancer cell is reported here by using an 18 O-substituted nucleoside [ 8 – 12 ] that is used to treat cells first and then combined with therapeutic protons. This approach is similar to using therapeutic protons to generate positron emitters from 12 C, 14 N, and 16 O atoms, which are short lived, and form the basis of in-room postproton positron emission tomography (PET) for range analysis that may be used to assess proton beam treatment accuracy [ 13 , 14 ].…”

Pd‐Catalyzed versus Uncatalyzed, PhI(OAc)2‐Mediated Cyclization Reactions of N6‐([1,1′‐Biaryl]‐2‐yl)Adenine Nucleosides

“…[1] Modified nucleosides have also impacted cancer therapeutics, hematological malignancies, and solid tumors, [2,3] and are important biological probes. [4] For these reasons and as yet undiscovered applications, studies of methods to rapidly modify the nucleoside structural scaffold are anticipated to remain a critical task. In one aspect of our studies, which also aim at understanding new reactivities of nucleoside substrates, we are interested in involving the purinyl nitrogen atoms in chemical transformations.…”