Application of Artificial Intelligence in Oncologic Molecular PET-Imaging: A Narrative Review on Beyond [18F]F-FDG Tracers Part II. [18F]F-FLT, [18F]F-FET, [11C]C-MET and Other Less-Commonly Used Radiotracers

Following the previous part of the narrative review on artificial intelligence (AI) applications in positron emission tomography (PET) using tracers rather than ¹⁸F-fluorodeoxyglucose ([¹⁸F]F-FDG), in this part we review the impact of PET-derived radiomics data on the diagnostic performance of other PET radiotracers, ¹⁸F-O-(2-fluoroethyl)-L-tyrosine ([¹⁸F]F-FET), ¹⁸F-Fluorothymidine ([¹⁸F]F-FLT) and ¹¹C-Methionine ([¹¹C]C-MET). [¹⁸F]F-FET-PET, using an artificial amino acid taken up into upregulated tumoral cells, showed potential in lesion detection and tumor characterization, especially with its ability to reflect glioma heterogeneity. [¹⁸F]F-FET-PET-derived textural features appeared to have the potential to reveal considerable information for accurate delineation for guiding biopsy and treatment, differentiate between low-grade and high-grade glioma and related wild-type genotypes, and distinguish pseudoprogression from true progression. In addition, models built using clinical parameters and [¹⁸F]F-FET-PET-derived radiomics features showed acceptable results for survival stratification of glioblastoma patients. [¹⁸F]F-FLT-PET-based characteristics also showed potential in evaluating glioma patients, correlating with Ki-67 and patient prognosis. AI-based PET-volumetry using this radiotracer as a proliferation marker also revealed promising preliminary results in terms of guide-targeting bone marrow-preserving adaptive radiation therapy. Similar to [¹⁸F]F-FET, the other amino acid tracer which reflects cellular proliferation, [¹¹C]C-MET, has also shown acceptable performance in predicting tumor grade, distinguishing brain tumor recurrence from radiation necrosis, and treatment monitoring by PET-derived radiomics models.

In addition, PET-derived radiomics features of various radiotracers such as [¹⁸F]F-DOPA, [¹⁸F]F-FACBC, [¹⁸F]F-NaF, [⁶⁸Ga]Ga-CXCR-4 and [¹⁸F]F-FMISO may also provide useful information for tumor characterization and predict of disease outcome.

In conclusion, AI using tracers beyond [¹⁸F]F-FDG could improve the diagnostic performance of PET-imaging for specific indications and help clinicians in their daily routine by providing features that are often not detectable by the naked eye.