Comparison of uptake between [18F]fluoro-α-methyltyrosine methoxy (18F-FAMT-OMe) and [18F] fluoro-α-methyltyrosine (18F-FAMT) in glioma xenograft mice.

Introduction: [¹⁸F]fluoro-α-methyltyrosine (¹⁸F-FAMT) is a promising PET probe for high specificity to L-type amino acid transporter 1 (LAT1), which is over-expressed on various malignant tumor cells. However, it is highly accumulated in kidney due to the affinity for organic anion transporter 1 (OAT1) and it also needs to be improved its low retention in the tumor. We have developed [¹⁸F]fluoro-α-methyltyrosine methoxy (¹⁸F-FAMT-OMe) to reduce its interaction to OAT1. The objective of the present study is to evaluate the tumor uptake and whole-body biodistribution of ¹⁸F-FAMT-OMe compared to ¹⁸F-FAMT in glioma xenograft mice.

Methods: BALB/c male nude mice (n=12, 7 weeks old, body weight=23.0±1.4g) were used 3 weeks after subcutaneous implantation of glioma cells (U-87MG, n=6 and C6 glioma, n=6). ¹⁸F-FAMT-OMe (n=6, 10.9 ± 0.5 MBq) and ¹⁸F-FAMT (n=6, 11.3 ± 1.2 MBq) were intravenously administrated into the mice via tail vein. 70 min of dynamic PET acquisition and static PET acquisition 60 min after injection were performed by microPET/CT scanner (SIEMENS INVEON). The mice were sacrificed and dissected after PET/CT for the collection of tumor and major organs including liver, both kidneys, pancreas, testes, and blood. The radioactivity of each organ was also measured by well-type gamma counter (BeWell).

Results: Dynamic PET acquisition with ¹⁸F-FAMT-OMe showed that uptakes in tumor and kidneys were rapidly increased after injection and peaked at 9-11 min in tumor and 5-7 min in kidneys and gradually decreased in U-87MG mice. SUVmean of ¹⁸F-FAMT-OMe were significantly higher than those of ¹⁸F-FAMT in C6 glioma bearing mice (1.29±0.18 and 0.38±0.27, respectively) (p<0.05). SUVmean of ¹⁸F-FAMT-OMe also showed higher trend compared to those of ¹⁸F-FAMT in U-87MG tumor bearing mice without statistical significance (0.90±0.14 and 0.68±0.27, respectively) (p>0.05). The SUVmean of ¹⁸F-FAMT-OMe were significantly higher than those of ¹⁸F-FAMT PET in liver (0.79±0.16 and 0.33±0.19), pancreas (3.57±1.17 and 1.14±0.85), and testes (0.69±0.22 and 0.26±0.12), respectively (p<0.01). SUVmean in kidney showed reduced trend on ¹⁸F-FAMT-OMe PET compared to ¹⁸F-FAMT administration (5.86±1.38 and 6.52±3.22, respectively), but there was no significant difference (p>0.05). The results of radioactivity measurement by BeWell showed corresponding results to PET.

Conclusions: The tumor uptake can be increased on ¹⁸F-FAMT-OMe PET compared to ¹⁸F-FAMT with increased radiotracer concentration in the blood. It was suggested that ¹⁸F-FAMT-OMe can improve the lesion detection for glioma compared to ¹⁸F-FAMT as well as the therapeutic application of radioligand therapy with improved tumor retention in the future.

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