Positron emission tomography (PET) imaging with (18)F-based radiotracers

Abstract

Positron Emission Tomography (PET) is a nuclear medicine imaging technique that is widely used in early detection and treatment follow up of many diseases, including cancer. This modality requires positron-emitting isotope labeled biomolecules, which are synthesized prior to perform imaging studies. Fluorine-18 is one of the several isotopes of fluorine that is routinely used in radiolabeling of biomolecules for PET; because of its positron emitting property and favorable half-life of 109.8 min. The biologically active molecule most commonly used for PET is 2-deoxy-2-(18)F-fluoro-β-D-glucose ((18)F-FDG), an analogue of glucose, for early detection of tumors. The concentrations of tracer accumulation (PET image) demonstrate the metabolic activity of tissues in terms of regional glucose metabolism and accumulation. Other tracers are also used in PET to image the tissue concentration. In this review, information on fluorination and radiofluorination reactions, radiofluorinating agents, and radiolabeling of various compounds and their application in PET imaging is presented.

Keywords: Fluorine-18; PET radiopharmaceuticals; positron emission tomography (PET).

Figure 1

Electrophilic fluorination; Syntheses of ¹⁸F-5-fluorouracil (A), ¹⁸F-a-trifluoromethyl ketones (B), and ¹⁸F-fluorodopa (C).

Figure 2

Electrophilic fluorination with ¹⁸F-perchloryl fluoride (A), synthesis of ¹⁸F-FDG (B), and radiosynthesis of the fluorinated A-ring of vitamin D₃ (C).

Figure 3

Nucleophilic fluorination; synthesis of ¹⁸F-FDG (A), and ¹⁸F-FHPG & ¹⁸F-FHBG (B).

Figure 4

synthesis of 2′- deoxy-2′-¹⁸F-fluoro-arabino-adenosine (A) and 3′- deoxy-3′-¹⁸F-fluoro-xylo-adenosine (B).

Figure 5

Four-step synthesis of 2′-deoxy-2′-¹⁸F-fluoro-1-β-D-5-substituted-arabionofuranosyluracil (A), and two-step synthesis of 2′-deoxy-2′-¹⁸F-fluoro-1-β-D-5-methyl-arabionofuranosyluracil (B).

Figure 6

Synthesis of ¹⁸F-FMXU (A), and ¹⁸F-FLT (B) and (C).

Figure 7

Nucleophilic fluorination, synthesis of synthesis of N³-substituted thymidine analogues.

Figure 8

Radiosynthesis of Et-¹⁸FDL (A) and ¹⁸F-FEL (B).

Figure 9

Nucleophilic fluorination, synthesis of ¹⁸F-F-PEG₆-IPQA.

Figure 10

Radiosynthesis of ¹⁸F-fluoroacetate (A), synthesis of ¹⁸F-Fmiso (B) and (C).

Figure 11

PET images of tumor-bearing mice using ¹⁸F-L-FMAU (A), ¹⁸F-D-FMAU (B), ¹⁸F-FLT (C), N³-¹⁸F-FET (D) and N³-¹⁸F-FPrT (E).

Figure 12

PET images of wild-type tumor (left flank) and HSV1-tk expressing tumor (right flank) on nude mice using ¹⁸F-FFAU (A), ¹⁸F-FCAU (B), ¹⁸F-FBAU (C), ¹⁸F-FIAU (D), ¹⁸F-FMAU (E), and ¹⁸F-FEAU (F). PET images of HSV1-tk and HSV1-A168Htk gene expression using ¹⁸F-FDG (G), ¹⁸F-FEAU (H) and ¹⁸F-FHBG (I).

Figure 13

PET images of 18F-FAA (A) and 18F-FXA (B); PET image of an orthotopically implanted pancreatic tumor xenograft in a nude mouse (C); and PET images of xenografts expressing EGFR using 18F-PEG6-IPQA in mice before therapy (D) and after therapy (E).