Emerging Radiopharmaceuticals in Pet Imaging for Mesothelioma: A Review of [18F]FDG Alternatives

Abstract

Mesothelioma is a malignant tumor associated primarily with asbestos exposure, characterized by an aggressive nature and poor prognosis. Accurate diagnosis, staging, and monitoring of therapeutic response are crucial for effective patient management. Along with a computed tomography (CT) scan, fluorodeoxyglucose labeled with fluorine-18 ([¹⁸F]FDG) positron emission tomography (PET) is commonly used in mesothelioma evaluation. However, it has some limitations, including lower sensitivity after pleurodesis and poor accuracy for involved lymph node evaluation. Thus, there is the need to explore other agents. The aim of the present review is to analyze the current literature on the use of alternative radiopharmaceuticals for PET imaging in patients with mesothelioma. A comprehensive search of scientific databases (PubMed, Scopus, and Web of Science) for studies published in the last decade was performed by using the following keywords: "mesothelioma" AND "PET" AND "PET/CT" "radiopharmaceuticals", "[¹⁸F]FDG alternatives". Articles focused solely on [¹⁸F]FDG, non-English publications or preclinical studies, reviews, meeting abstracts, letters to the editors, and editorials were excluded. A qualitative assessment was made by using the Critical Appraisal Skills Programme (CASP) checklist for diagnostic test studies, when applicable. In total, 14 papers were selected; in seven articles more than five patients were enrolled, while the other seven were only clinical cases (enrolling up to two subjects). [¹⁸F]/gallium-68 ([⁶⁸Ga])-labeled fibroblast activation protein inhibitor (FAPI) compounds, [¹⁸F]Fluorothymidine ([¹⁸F]FLT), methionine labeled with carbon-11 ([¹¹C]MET), and fluoromisonidazole labeled with fluorine-18 ([¹⁸F]FMISO) PET/CT were the alternative agents used most often. In 12 articles, [¹⁸F]FDG PET/CT was used as a comparator imaging modality. Detection rate of [¹⁸F]FDG was similar to the other radiopharmaceuticals ([⁶⁸Ga]/[18F]-labeled FAPI compounds, [¹⁸F]FLT, [¹⁸F]FMISO, [¹¹C]MET, and [⁶⁸Ga]-Pentaxifor), although radiolabeled FAPI seems to exhibit a higher diagnostic performance. [¹⁸F]FDG is still a valuable agent in patients with mesothelioma. However, radiolabeled FAPI appears to be promising and its theranostic properties should therefore be further assessed.