Synthesis and Evaluation of [¹⁸F] Labeled Pyrimidine Nucleosides for Positron Emission Tomography Imaging of Herpes Simplex Virus 1 Thymidine Kinase Gene Expression

Abstract

Synthesis of three novel 2'-deoxy-2'-[18F]fluoro-1-beta-D-arabinofuranosyluracil derivatives [18F]FPAU, [18F]FBrVAU, and [18F]FTMAU is reported. The compounds were synthesized by coupling of 1-bromo-2-deoxy-2-fluoro sugars with corresponding silylated uracil derivatives. In vitro cell uptake indicated that all three compounds are taken up selectively in RG2TK+ cells with negligible uptake in RG2 cells. The results indicate that [18F]FBrVAU and [18F]FTMAU have better uptake profiles in comparison to [18F]FPAU and have potential as PET probes for imaging HSV1-tk gene expression.

Applications of nuclear-based imaging in gene and cell therapy: Probe considerations

“…In such scenarios a surrogate gene, also called as reporter gene (e.g., herpes simplex virus type 1-thymidine kinase [HSV1-tk], norepinephrine transporter [NET], sodium iodide symporter [NIS]), that can be targeted using a radiochemical probe can be expressed as a fusion protein or as a separate protein using bi-or multi-cistronic vectors that will ensure a stoichiometric expression of the gene product. [10][11][12][13][14] For gene therapy involving RNAi technology, direct labeling of RNAi with a suitable radiolabeled conjugate can provide information about the delivery of the vector. 15 Irrespective of the type of imaging approach, the design, function, and pharmacokinetic behavior of the radiochemical probe is the most crucial determinant in ensuring that the signal obtained using the radiochemical probe directly correlates to the efficacy of gene therapy.…”

Recent advances in the synthesis of fluorinated nucleosides

“…[376][377][378][379][380][381] Their synthesis featured that the 18 383 The key nosylate precursor 1083 was prepared, with an overall yield of 9.4%, from uridine 10 in four steps. Oh 384,385 Either Bu 4 N 18 F or K 18 F could be used as the fluorinating agent, although, Bu 4 N 18 F has advantages in view of its good solubility in organic solvents and low reaction temperature.…”

Synthesis and radiolabelling of Re(CO)3‐β‐elemene derivatives as potential therapeutic radiopharmaceuticals

“…Then, 5 mL of each layer was pipetted into other test tubes, and log P values were calculated using the formula: Log P = Log (counts in octanol/counts in water). 18 …”