Fibroblast activation protein (FAP), overexpressed on cancer-associated fibroblasts (CAFs), is a novel target for molecular imaging of various tumors. Recently, the development of several small-molecule FAP inhibitors for radiolabeling with ⁶⁸Ga has resulted in the emergence of studies evaluating its clinical role in cancer imaging. Preliminary findings have demonstrated that, in contrast to radiotracers taking advantage of cancer-specific targets such as PSMA and DOTATATE, FAPs as a target are the most promising that can compete with ¹⁸FDG in terms of widespread indications. They also have the potential to overcome the shortcomings of ¹⁸FDG, particularly false-positive uptake due to inflammatory or infectious processes, low sensitivity in certain cancer types, and radiotherapy planning. In addition, the attractive theranostic properties may facilitate the treatment of many refractory cancers. This review summarizes the current FAP variants and related clinical studies, focusing on radiopharmacy, dosimetry, and diagnostic and theranostic applications.

Fibroblast-activation protein is a promising target for oncologic molecular imaging. Studies show that fibroblast activation protein inhibitor (FAPI) radiotracers are accurate diagnostics with favorable tumor-to-background ratios across various cancers. Therefore, we performed a systematic review and metaanalysis to assess the diagnostic performance of FAPI PET/CT in comparison with [¹⁸F]FDG PET/CT, the most widely used radiotracer in oncology. Methods: We conducted a systematic search in MEDLINE, Embase, Scopus, PubMed, Cochrane Central Register of Controlled Trials, relevant trial registries, and bibliographies. The search consisted of combinations of terms for 3 topics: neoplasia, PET/CT, and FAPI. Two authors independently screened retrieved articles using predefined inclusion and exclusion criteria and extracted the data. Study quality was assessed using the criteria of QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). For each study, the sensitivity, specificity, and 95% CIs were calculated to determine diagnostic accuracy for primary, nodal, and metastatic lesions. A random-effects metaanalysis was used for pooling the data, and heterogeneity was assessed (I² index). Results: Thirty-nine studies (1,259 patients) investigating the use of FAPI PET/CT were included. On a patient-based analysis, pooled sensitivity was 0.99 (95% CI, 0.97–1.0) for the detection of primary lesions. Pooled sensitivity for nodal and distant metastases was 0.91 (95% CI, 0.81–0.96) and 0.99 (95% CI, 0.96–1.0), respectively. On a paired analysis between FAPI and [¹⁸F]FDG PET/CT, FAPI had a higher sensitivity in the detection of primary, nodal, and metastatic lesions (all P < 0.001). The differences in sensitivities between FAPI and [¹⁸F]FDG were statistically significant. In terms of heterogeneity, analyses on primary lesions were moderately affected, distant metastatic lesions were highly affected, and the nodal metastatic analyses had negligible heterogeneity. Conclusion: The diagnostic performance of FAPI PET/CT is superior to that of [¹⁸F]FDG in the detection of primary, nodal, and distant metastases. However, further studies are needed to better evaluate its utility and indication in specific cancer types and clinical settings. Visual Abstract

The aim of this narrative review is to evaluate the current status of ¹⁷⁷Lu-PSMA (prostate specific membrane antigen) therapy for metastatic castration-resistant prostate cancer (mCRPC) in the light of the current literature. We also addressed patient preparation, therapy administration and side effect profiles. ¹⁷⁷Lu-PSMA therapy efficacy was assessed by using prospective trials, meta-analyses and major retrospective trials. Predictors of efficacy were also mentioned. Although there are some different approaches regarding the use of ¹⁷⁷Lu-PSMA therapy in different countries, this type of therapy is generally safe, with a low toxicity profile. From the oncological point of view, a PSA (prostate specific antigen) decline of ≥50% was seen in 10.6–69% of patients with mCRPC; whereas progression-free survival (PFS) was reported to be 3–13.7 months in different studies. Consequently, ¹⁷⁷Lu-PSMA therapy is a promising treatment in patients with mCRPC, with good clinical efficacy, even in heavily pretreated patients with multiple lines of systemic therapy. Currently, there are ongoing clinical trials in the United States, including a phase III multicenter FDA registration trial.

To our knowledge, no prior multicenter clinical trial has reported interobserver agreement of ¹⁸F-FDG PET/CT scans for staging of clinical N0 neck in head and neck cancer. Methods: A total of 287 participants were recruited. For visual analysis, positive nodal uptake of ¹⁸F-FDG was defined as uptake visually greater than activity seen in the blood pool. Results: The negative predictive value of the ¹⁸F-FDG PET/CT for N0 clinical neck was 86% or above for visual assessment (95% CI, 86%–88%) for the 2 central readers and above 90% (95% CI, 90%–95%) for SUV_max for central reads and site reads dichotomized at the optimal cutoff value of 1.8 and the prespecified cutoff value of 3.5, respectively. The κ coefficients between the 2 expert readers and between central reads and site reads varied between 0.53 and 0.78. Conclusion: The NPV of the ¹⁸F-FDG PET/CT for N0 clinical neck was 86% or above for visual assessment and above 90% for SUV_max cut points of 1.8 and 3.5 with moderate to substantial agreements.