L-3-[18F]-Fluoro-α-Methyl Tyrosine as a PET Tracer for Tumor Diagnosis: A Systematic Review from Mechanisms to Clinical Applications

Abstract

L-3-[¹⁸F]-fluoro-α-methyl tyrosine ([¹⁸F]FAMT) is an amino acid positron emission tomography (PET) tracer with high specificity for malignant tumors through its selective transport via L-type amino acid transporter (LAT) 1. Although extensively studied for its diagnostic performance, a comprehensive review of its molecular and clinical characteristics remains lacking. A systematic literature review (1997-2025) was conducted using PubMed and Web of Science, with keywords including "L-3-[¹⁸F]-fluoro-α-methyl tyrosine", "[¹⁸F]FAMT", "amino acid PET", and "tumor imaging". The review covered aspects of synthesis, structural properties, pharmacokinetics, and clinical applications. Notably, while research on [¹⁸F]FAMT has declined significantly in recent years, [¹⁸F]FAMT PET demonstrates superior specificity to [¹⁸F]FDG PET in distinguishing malignancies from inflammatory lesions and offers distinct advantages in lung, esophageal, and oral cancers, though with slightly lower sensitivity. Its key features include tumor-specific uptake patterns, rapid blood clearance, and a significant correlation between its uptake levels and both LAT1 expression and tumor proliferation. In conclusion, [¹⁸F]FAMT is a promising PET tracer with notable advantages in tumor imaging, particularly due to its LAT1 selectivity and favorable pharmacokinetics. Despite challenges in production, these characteristics underscore its clinical value in cancers requiring precise imaging. Future research should focus on optimizing synthesis, expanding clinical validation, and exploring theranostic applications.

Keywords: LAT1; [18F]FAMT; amino acid PET; molecular imaging; treatment response assessment; tumor diagnosis.

Figure 1

[¹⁸F]FAMT flowchart of the article selection process.

Figure 2

Number of articles for [¹⁸F]FAMT from 1997 to 2025.

Figure 3

Structural characteristics of [¹⁸F]FAMT (A) and D-[¹⁸F]FAMT (B).

Figure 4

[¹⁸F]FAMT transport via L-type amino acid transporter 1. [¹⁸F]FAMT (represented by star symbols) is selectively transported across the cell membrane by LAT1 (blue). LAT1 forms a functional heterodimeric complex with 4F2hc (yellow) via a disulfide bond (S–S), enabling the specific uptake of [¹⁸F]FAMT from the extracellular to the intracellular compartment (red dotted arrow). In contrast, other amino acid transporters (orange) do not significantly contribute to [¹⁸F]FAMT uptake, as indicated by the red X, highlighting the high substrate selectivity of this radiotracer for LAT1-mediated transport.

Figure 5

Anatomical biodistribution profile of [¹⁸F]-FAMT.

Figure 6

Clinical applications of [¹⁸F]FAMT PET. [¹⁸F]FAMT demonstrates diagnostic value in various malignancies (oral cancer, glioma, breast cancer, multiple myeloma, lung cancer, and esophageal cancer) and shows utility in differentiating malignant lesions from inflammatory conditions (sarcoidosis).