FAPI-based radiopharmaceuticals are a novel class of tracers, mainly used for PET imaging, which have demonstrated several advantages over [¹⁸F]FDG, especially in the case of low-grade or well-differentiated tumors. We conducted this systematic review to evaluate all the studies where a head-to-head comparison had been performed to explore the potential utility of FAPI tracers in clinical practice. FAPI-based radiopharmaceuticals have shown promising results globally, in particular in detecting peritoneal carcinomatosis, but studies with wider populations are needed to better understand all the advantages of these new radiopharmaceuticals.

In the era of precision medicine, the optimization of oncological patient management with early and accurate tumor response assessment is crucial. In this scenario, [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography/computed tomography (PET/CT) has gained an important role in providing prognostically relevant information. The first PET-based scoring system proposed in 1999 was the well-known European Organization for Research and Treatment of Cancer (EORTC) criteria. From that moment on and over the last 20 years, several PET/CT criteria have emerged and have been adapted to enhance the response assessment for specific tumor types and/or therapies, with only a few of them endorsed by guidelines. In this literature systematic review, we aimed to list and discuss the most relevant PET/CT criteria proposed for solid and non-solid [¹⁸F]FDG-avid tumors. A literature search extended until November 2022 on the PubMed/MEDLINE database was conducted. The criteria used to assess the response were first classified according to treatment type and specific cancer type. Then, the main findings of the criteria were analyzed and discussed. A widespread effort to standardize and identify the best [¹⁸F]FDG PET response criteria tailored for each oncological treatment emerged, also considering the introduction of new biological therapeutic agents and the increasingly essential post-treatment application of [¹⁸F]FDG PET/CT in different cancer diseases. To improve their impact on daily clinical practice, however, most of the proposed criteria need to be further validated.

Recent European guidelines recommend using brain FDG-PET to differentiate between Alzheimer’s disease (AD) and depressive pseudodementia (DP), with specific hypometabolism patterns across the former group, and typically normal or frontal hypometabolism in the latter. We report the case of a 74 years-old man with DP (MMSE 16/30), whose FDG-PET visual rating and semiquantitative analysis closely mimicked the typical AD pattern, showing severe hypometabolism in bilateral precuneus, parietal and temporal lobes, and sparing frontal areas, suggesting the diagnosis of moderate AD. Shortly after starting antidepressant polytherapy, he underwent formal NPS testing, which revealed moderate impairment of episodic memory and mild impairment on executive and visuospatial tests, judged consistent with neurodegenerative dementia and concomitant depression. Over the following two years, he improved dramatically: repeated NPS assessment did not show significant deficits, and FDG-PET showed restoration of cerebral metabolism. The confirmation of PET findings via semiquantitative analysis, and their reversion to normality with antidepressant treatment, proved the non-neurodegenerative origin of the initial AD-like FDG-PET abnormalities. We review similar cases and provide a comprehensive analysis of their implications, concluding that reversible FDG-PET widespread hypometabolism might represent a biomarker of pseudodementia. Therefore, we suggest caution when interpreting FDG-PET scans of depressed patients with cognitive impairment.