Multicenter Reproducibility of ¹⁸F-Fluciclatide PET Imaging in Subjects with Solid Tumors

Abstract

Integrins are upregulated on both tumor cells and associated vasculature, where they play an important role in angiogenesis and metastasis. Fluciclatide is an arginine-glycine-aspartic acid peptide with high affinity for α v β 3 /α v β 5 integrin, which can be radiolabeled for PET imaging of angiogenesis. Thus, 18 F-fluciclatide is a potential biomarker of therapeutic response to antiangiogenic inhibitors. The aim of this study was to evaluate the reproducibility of 18 F-fluciclatide in multiple solid-tumor types. Methods: Thirtynine patients underwent PET/CT scanning at 40, 65, and 90 min after injection of 18 F-fluciclatide (maximum, 370 MBq) on 2 separate days (2-9 d apart). Patients did not receive any therapy between PET/CT scans. 18 F-fluciclatide images were reported and quantitative measures of uptake were extracted using the PERCIST methodology. Intrasubject reproducibility of PET uptake in all measurable lesions was evaluated by calculating relative differences in SUV between PET scans for each lesion during the 2 imaging sessions. Results: Thirty-nine measurable lesions were detected in 26 patients. Lesion uptake correlated strongly across imaging sessions (r 5 0.92, P , 0.05, at 40 min; r 5 0.94, P , 0.05, at 65 min; r 5 0.94, P , 0.05, at 90 min) with a mean relative difference and SD of the relative difference of 0.006 ± 0.18 at 40 min, 0.003 ± 0.19 at 65 min, and 0.025 ± 0.20 at 90 min. This reflects 95% limits of repeatability of 35%-39% for the difference between the 2 SUV measurements or a variability of 18%-20% in agreement from that observed in well-calibrated multicenter 18 F-FDG studies. Conclusion: The test-retest reproducibility of 18 F-fluciclatide across multiple tumor types has been measured and shown to be acceptable. This is an important step in the development of this in vivo biomarker to identify and quantify response to antiangiogenic therapy in cancer patients.

Integrin Signaling in Cancer: Mechanotransduction, Stemness, Epithelial Plasticity, and Therapeutic Resistance

“…Integrin overexpression in tumor cells and their vasculature have opened the door to integrin-targeted probes for non-invasive medical imaging and development of biomarkers. RGD-based 18 F- and 68 Ga-PET (positron emission tomography) was developed to exploit tumor-selective αv expression, where 18 F-fluciclatide detects an array of solid cancers and is being explored clinically (Sharma et al, 2015). 68 Ga-linked bombesin-RGD is in early development for co-targeting αv integrins and gastrin-releasing peptide receptor, with promising clinical efficacy in probing prostate tumors and metastases (Zhang et al, 2017).…”

Real-time near-infrared fluorescence imaging using cRGD-ZW800-1 for intraoperative visualization of multiple cancer types

“…cRGD-ZW800-1 may therefore act as a generic tracer for a broad variety of solid tumors. Indeed, various phase I and II clinical trials with RGD-based PET tracers have shown uptake in multiple tumor types, including melanomas, glioblastomas, breast, colorectal, ovarian, cervical, non-small cell lung, neuroendocrine, head and neck, and pancreatic cancer [11–14]. Preliminary work on the development of cRGD-ZW800-1 showed low non-specific uptake and excellent in vivo properties in tumor xenograft mouse models [15, 16].…”

[18F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer

“…Single-bed, dynamic scans were conducted in order to understand the effect of the drug tracer kinetics, consequently to confirm the most practical time for imaging when [ 18 F]fluciclatide is used as an imaging test in monitoring the effect of antiangiogenic therapy. We anticipate that future studies employing [ 18 F]fluciclatide will build on our work to implement a more standard static, multi-bed whole-/half-body imaging protocol in a larger study population [41]. Finally, preclinical work suggests that normalization of vessels in response to anti-angiogenics occurs within hours and lasts 7-10 days, and the optimal timing of imaging this process remains to be established, and it is possible that performing the second PET scan at 7 days may have missed the neovascularization window [45].…”

“…2). Previous work by our group defined an objective response to [ 18 F]fluciclatide statistically as a change in SUV 60,mean outside the 95% confidence limits, such that for any given lesion a change in SUV > 18% will be outside these limits and classified as a [ 18 F]fluciclatide response [41]. Based on this, [ 18 F]fluciclatide response was seen in 15 of 27 lesions (56%), with 2 lesions no longer being visible on post-treatment scans (Fig.…”