Synthesis and biological evaluation of O-\[3-18F-fluoropropyl\]-α-methyl tyrosine in mesothelioma-bearing rodents

Our plain-English summary of Synthesis and biological evaluation of O-[3-18F-fluoropropyl]-α-methyl tyrosine in mesothelioma-bearing rodents, by I.H. Shih, F.L. Kong, M.S. Ali, et al (BioMed Research International, 2013).

The study

• Authors: I.H. Shih, F.L. Kong, M.S. Ali, Y. Zhang, D.F. Yu, X. Duan, D.J. Yang
• Journal: BioMed Research International
• Published: 2013;2013:460619
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Radiolabeled tyrosine analogs enter cancer cells via upregulated amino acid transporter system and have been shown to be superior to (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) in differential diagnosis in cancers. In this study, we synthesized O-[3-(19)F-fluoropropyl]-α-methyl tyrosine ((19)F-FPAMT) and used manual and automated methods to synthesize O-[3-(18)F-fluoropropyl]-α-methyl tyrosine ((18)F-FPAMT) in three steps: nucleophilic substitution, deprotection of butoxycarbonyl, and deesterification. Manual and automated synthesis methods produced (18)F-FPAMT with a radiochemical purity >96%. The decay-corrected yield of (18)F-FPAMT by manual synthesis was 34% at end-of-synthesis (88 min). The decay-corrected yield of (18)F-FPAMT by automated synthesis was 15% at end-of-synthesis (110 min). (18)F-FDG and (18)F-FPAMT were used for in vitro and in vivo studies to evaluate the feasibility of (18)F-FPAMT for imaging rat mesothelioma (IL-45). In vitro studies comparing (18)F-FPAMT with (18)F-FDG revealed that (18)F-FDG had higher uptake than that of (18)F-FPAMT, and the uptake ratio of (18)F-FPAMT reached the plateau after being incubated for 60 min. Biodistribution studies revealed that the accumulation of (18)F-FPAMT in the heart, lungs, thyroid, spleen, and brain was significantly lower than that of (18)F-FDG. There was poor bone uptake in (18)F-FPAMT for up to 3 hrs suggesting its in vivo stability. The imaging studies showed good visualization of tumors with (18)F-FPAMT. Together, these results suggest that (18)F-FPAMT can be successfully synthesized and has great potential in mesothelioma imaging.

In plain English

This was a laboratory and animal study, not a study of asbestos exposure in people. Researchers at The University of Texas MD Anderson Cancer Center made a new radioactive tracer for PET scans, called 18F-FPAMT, a modified form of the amino acid tyrosine. They tested whether it could show mesothelioma tumors grown in rats from injected rat mesothelioma cells (IL-45). Made by hand, the tracer had a decay-corrected yield of 34% in 88 minutes. Made with the authors' own automated machine, the yield was 15% in 110 minutes. In mesothelioma cells grown in dishes, the standard tracer 18F-FDG was taken up more than 18F-FPAMT at every time point. In tumor-bearing female Fischer rats (three per tracer at each time point), the authors reported lower 18F-FPAMT than 18F-FDG in the heart, lungs, thyroid, spleen and brain, but high 18F-FPAMT uptake in the kidneys and pancreas. Tumors could be seen on scans with both tracers. The tumor-to-muscle ratio was 2.82 for 18F-FPAMT and 8.26 for 18F-FDG. The authors concluded that 18F-FPAMT can be a good PET agent for detecting mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory chemistry study (synthesis of a PET tracer) with an in vitro cell-uptake experiment and an animal experiment (biodistribution and PET imaging in rats), compared against the standard tracer 18F-FDG
• Who was studied: Rat mesothelioma IL-45 cells in culture, and female Fischer rats (140 to 185 g) inoculated with IL-45 cells at the hind leg, housed at The University of Texas MD Anderson Cancer Center. Each tracer was injected into 9 rats, 3 rats per time point.
• Exposure: No asbestos exposure was studied. The rats were given the experimental radiotracer 18F-FPAMT or the standard tracer 18F-FDG by intravenous injection (30 microcuries per rat for biodistribution, 500 microcuries for PET imaging).
• Main results:
  • Manual synthesis produced 10 mCi of 18F-FPAMT with a decay-corrected yield of 34% at end of synthesis (88 min)
  • Automated synthesis gave a decay-corrected yield of 15% with an end-of-synthesis time of 110 min
  • In IL-45 mesothelioma cells, 18F-FPAMT uptake leveled off at 60 min, while 18F-FDG uptake kept rising and was higher than 18F-FPAMT at each time point
  • In tumor-bearing rats, the authors reported 18F-FPAMT accumulation lower than 18F-FDG in heart, lungs, thyroid, spleen and brain, and high 18F-FPAMT accumulation in kidneys and pancreas. For example, kidneys were 3.86 plus or minus 0.74 percent of injected dose per gram at 30 min with 18F-FPAMT, and brain was 0.02 with 18F-FPAMT versus 2.36 with 18F-FDG at 30 min.
  • On PET scans, tumors could be clearly detected with both tracers. The tumor-to-muscle SUV ratio was 2.82 for 18F-FPAMT and 8.26 for 18F-FDG.
  • Radiation doses estimated for a reference human adult from the rat data were below US FDA limits for each organ at a proposed dose of 30 mCi per patient
• The authors' conclusion: The authors concluded that their in vitro and in vivo studies suggested 18F-FPAMT can be a good PET agent for detecting mesothelioma, and that it might have potential in brain tumor imaging.
• Limitations the authors state:
  • The authors described the animal work as a preliminary evaluation and said the automated process still needs optimization for better yield and higher specific activity

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, F-fluoro-2-deoxy-D-glucose (FDG), Differential Diagnosis.

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