The diagnostic performance of 18F-FAMT PET and 18F-FDG PET for malignancy detection: a meta-analysis

Abstract

BackgroundThis meta-analysis aims to compare the diagnostic performance of l-3-18F-α-methyl tyrosine (18F-FAMT) positron emission tomography (PET) and 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) PET for malignancy detection.MethodsThe workflow of this study follows Cochrane Collaboration Guidelines of a systematic review of diagnostic test accuracy studies. An electronic search was performed for clinical diagnostic studies directly comparing 18F-FAMT and 18F-FDG PET for malignant tumors. Study quality, the risks of bias and sources of variation among studies were assessed using the QUADAS (Quality Assessment of Diagnostic Accuracy Studies) assessment tool. A separate meta-analysis was performed for diagnostic performance based on visual assessment and diagnostic cut-off values. Whenever possible, a bivariate random-effect model was used for analysis and pooling of diagnostic measures across studies.ResultsElectronic search revealed 56 peer-reviewed basic science investigations and clinical studies. Six eligible studies (272 patients) of various type of cancer were meta-analyzed. The 18F-FAMT diagnostic accuracy for malignancy was higher than 18F-FDG based on both visual assessment (diagnostic odd ratio (DOR): 8.90, 95% confidence interval (CI) [2.4, 32.5]) vs 4.63, 95% CI [1.8, 12.2], area under curve (AUC): 77.4% vs 72.8%) and diagnostic cut-off (DOR: 13.83, 95% CI [6.3, 30.6] vs 7.85, 95% CI [3.7, 16.8], AUC: 85.6% vs 80.2%), respectively. While the average sensitivity and specificity of 18F-FAMT and 18F-FDG based on visual assessment were similar, 18F-FAMT was significantly more specific than 18F-FDG (p < 0.05) based on diagnostic cut-off values.Conclusions 18F-FAMT is more specific for malignancy than 18F-FDG, while their sensitivity is comparable. 18F-FAMT PET is equal to 18F-FDG PET in diagnostic performance for malignancy detection in several cancer types.

α‐Emitting cancer therapy using 211At‐AAMT targeting LAT1

“…FDG has the potential for false-positive accumulation within inflammation related to high glucose metabolism in macrophages or neutrophils, whereas 18 F-FAMT accumulates in tumors via LAT1, which is expressed only in cancer cells. 20 In contrast, 18 F-FAMT is not transported by other isoforms of the system L (eg, LAT2, LAT3, and LAT4), which are expressed in normal tissues. 21,22 Therefore, our l-3-[ 211 At]-α-methyl-tyrosine ( 211 At-AAMT) reagent is also expected to have LAT1 specificity and potential as a TAT treatment ( Figure S1).…”

“…In particular, l ‐3‐[ 18 F]‐α‐methyl‐tyrosine ( 18 F‐FAMT) has higher potential for tumor specificity compared with 2‐deoxy‐2‐[ 18 F]fluoro‐glucose ( 18 F‐FDG), which is widely employed as a PET probe for cancer staging. FDG has the potential for false‐positive accumulation within inflammation related to high glucose metabolism in macrophages or neutrophils, whereas 18 F‐FAMT accumulates in tumors via LAT1, which is expressed only in cancer cells 20 . In contrast, 18 F‐FAMT is not transported by other isoforms of the system L (eg, LAT2, LAT3, and LAT4), which are expressed in normal tissues 21,22 .…”

Highly Specific L-Type Amino Acid Transporter 1 Inhibition by JPH203 as a Potential Pan-Cancer Treatment

“…The very low LAT1 expression in normal cells (only expressed in the BBB epithelial cells, placenta, monocytes, macrophages, testis, and pancreatic β cells) makes LAT1 an ideal cancer molecular target for therapy [21]. LAT1 has long been the target of diagnostic oncology imaging using the positron emission tomography (PET) radiopharmaceutical 3-[ 18 F]-fluoro-L-α-methyl tyrosine ([ 18 F]-FAMT), a LAT1-specific substrate [38,39]. Although the LAT1 specificity of FAMT has been elucidated [40], the development of [ 18 F]-FAMT-alike (small) substrate-based therapeutic targeted drugs will not be of much use because of the two-way LAT1 transport properties (one amino acid influx is always exchanged for one amino acid efflux out of the cell).…”

Next-Generation Molecular Imaging of Thyroid Cancer

“…Most transporter-targeting probes are small-size molecules, carried into the intracellular space by transporters on the cell surface. Some transporter-associated probes may take part in cell metabolism [20,21]. Many transporter-based isotopes, including radioiodine, are routinely to image the recurrence and metastases of TC.…”