Response Assessment of ⁶⁸Ga-DOTA-E-[c(RGDfK)]² PET/CT in Lung Adenocarcinoma Patients Treated with Nintedanib Plus Docetaxel

Abstract

Nintedanib is an oral angiokinase inhibitor used as second-line treatment for non-small cell lung cancer. New radiotracers, such as Ga-DOTA-E-[c(RGDfK)], that target αβ integrin might have an impact as a noninvasive method for assessing angiogenesis inhibitors. From July 2011 through October 2015, 38 patients received second-line nintedanib plus docetaxel. All patients underwent PET/CT withGa-DOTA-E-[c(RGDfK)] radiotracer and blood-sample tests to quantify angiogenesis factors (fibroblast growth factor, vascular endothelial growth factor, and platelet-derived growth factor AB) before and after completing 2 therapy cycles. Of the 38 patients, 31 had available baseline and follow-up PET/CT. Baseline lung tumor volume addressed withGa-DOTA-E-[c(RGDfK)] PET/CT correlated with serum vascular endothelial growth factor levels, whereas baseline lung/liver SUV index correlated with platelet-derived growth factor AB. After treatment, the overall response rate and disease control rate were 7.9% and 47.3%, respectively. A greater decrease in lung tumor volume (-37.2% vs. -27.6%) was associated with a better disease control rate in patients ( = 0.005). Median progression-free survival was 3.7 mo. Nonsmokers and patients with a higher baseline lung tumor volume were more likely to have a higher progression-free survival (6.4 vs. 3.74 [ = 0.023] and 6.4 vs. 2.1 [ = 0.003], respectively). Overall survival was not reached. Patients with a greater decrease in lung SUV (not reached vs. 7.1 mo; = 0.016) and a greater decrease in the lung/spleen SUV index (not reached vs. 7.1; = 0.043) were more likely to have a longer overall survival.Ga-DOTA-E-[c(RGDfK)] PET/CT is a potentially useful tool for assessing responses to angiogenesis inhibitors. Further analysis and novel studies are warranted to identify patients who might benefit from this therapy.

Imaging angiogenesis in patients with head and neck squamous cell carcinomas by [68Ga]Ga-DOTA-E-[c(RGDfK)]2 PET/CT

“…Because data on the in vivo biodistribution and kinetics of the dimeric 68 Ga-RGD in patients is limited [ 15 , 21 ] and non-existent for HNSCC, we investigated detailed tissue distribution kinetics in this study. A fast blood clearance was observed using the PET/CT images as image-derived input function, with a venous distribution half-life of 0.14 ± 0.07 min and an elimination half-life phase of 18.6 ± 7.42 min.…”

“…In recent years, many studies focused on the potential of molecular imaging with RGD-containing peptides targeting α v β 3 integrins [ 12 ]. Several monomeric and multimeric 68 Ga-labelled RGD compounds have been developed and were studied in glioblastoma [ 13 ], cervical and ovarian cancer [ 14 ] and lung adenocarcinoma [ 15 ]. The dimeric radiotracer [ 68 Ga]Ga-DOTA-E-[c(RGDfK)] 2 ( 68 Ga-RGD) has preclinically shown its potential for imaging of angiogenesis in HNSCC [ 16 , 17 ], but only limited data from clinical studies is available.…”

Integrin-targeted quantitative optoacoustic imaging with MRI correlation for monitoring a BRAF/MEK inhibitor combination therapy in a murine model of human melanoma

“…The role of optoacoustic imaging compared to alternative α v ß 3 -integrin-targeted imaging modalities remains to be defined. Positron emission tomography (PET) with targeted radionuclides as well as MRI using targeted contrast agents also allow for the non-invasive characterization of α v ß 3 -integrin receptor status in vivo [ 13 , 37 – 39 ]. Compared to optoacoustic imaging, these modalities are not limited by low tissue penetration depth and are superior with regard to whole-body tumor staging.…”

68Ga-DOTA-E-[c(RGDfK)]2 positron emission tomography–computed tomography in the evaluation of hepatic hemangioendothelioma epithelioid

“…68 Ga-DOTA-E-[(RGDfK)c]2 (68Ga-DOTA-RGD) is a radiotracer that targets integrin αvβ3, and may have an impact as a noninvasive method for assessing neovascularization and allows the follow-up and evaluation of response to the treatment of many pathologies. 3…”