ArticleEJNMMI research2026
Combined antitumor activity of [
Article in EJNMMI research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Corrections and comments
- Erratum issued
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8 authors.
Funding
Abstract
backgroundSarcomas comprise a heterogeneous group of aggressive mesenchymal malignancies with limited therapeutic options and poor prognosis, underscoring the need for novel treatment strategies. Fibroblast activation protein (FAP), which is highly expressed on sarcoma-associated fibroblasts within the tumor microenvironment, has emerged as a promising target for precision radioligand therapy. To evaluate this approach, we employed a patient-derived xenograft (PDX) sarcoma mouse model to investigate [177Lu]Lu-FAPI-2286 radioligand therapy. Therapeutic efficacy was assessed longitudinally in vivo using [18F]F-FAPI-74 PET imaging and subsequently corroborated by pathological analyses.
resultsThe radiosynthesis of both [18F]F-FAPI-74 (n = 8) and [177Lu]Lu-FAPI-2286 (n = 3) achieved high radiochemical purity (> 95%), confirming their suitability for subsequent applications. Both tracers showed similar biodistribution patterns with predominant renal clearance. MicroPET imaging demonstrated clear [18F]F-FAPI-74 uptake in PDX sarcomas (SUVmean = 0.60 ± 0.12), and microSPECT imaging revealed detectable [177Lu]Lu-FAPI-2286 tumor uptake (SUVmean = 0.20 ± 0.18). In the in vivo evaluation of therapeutic efficacy, the combination therapy ([177Lu]Lu-FAPI-2286 + pazopanib) demonstrated the most pronounced antitumor effect, suppressing tumor growth by approximately six-fold compared with the control group, without inducing body weight loss or overt toxicity. Longitudinal [18F]F-FAPI-74 PET imaging revealed markedly decreased tracer uptake in the combination group (SUVmean = 0.68 ± 0.20) compared with the control (SUVmean = 1.42 ± 0.47) and pazopanib monotherapy (SUVmean = 1.22 ± 0.11) groups. Immunohistochemical analysis confirmed reduced FAP expression (− 38% versus control), decreased Ki-67 proliferation index (− 70%), and elevated cleaved caspase-3 levels (~ 2-fold increase) in radioligand-treated tumors, indicating enhanced apoptosis and an improved therapeutic response.
conclusions[177Lu]Lu-FAPI-2286 demonstrated significant therapeutic potential against sarcoma in our preclinical model, with an apparent enhancement when combined with pazopanib. Additionally, [18F]F-FAPI-74 PET imaging proved valuable as a non-invasive radiotracer for treatment monitoring. These findings provide strong preclinical evidence supporting the advancement of FAP-targeted radioligand therapy in combination with pazopanib into clinical trials.
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