Abstract
Objectives
This study was designed to investigate the efficacy of 99mtechnetium-three polyethylene glycol spacers-arginine–glycine–aspartic acid ([99mTc]3PRGD2) in the evaluation of patients with esophageal cancer.
Methods
Twenty-nine patients with a suspected esophageal lesion and for whom definite pathological diagnosis was finally obtained were recruited. Whole-body planar scanning and chest single-photon-emission computed tomography/computed tomography (SPECT/CT) were performed at 30 and 40 min, respectively, after intravenous injection of 11.1 MBq/kg of [99mTc]3PRGD2. 2-Deoxy-2-[18F] fluoro-d-glucose ([18F]FDG) positron-emission tomography/computed tomography (PET/CT) was performed in 1 week. The tumor-to-background ratio (T/B) and the maximum standard uptake value (SUVmax) were calculated for semi-quantitative and quantitative analyses. Integrin αvβ3 was analyzed through immunohistochemistry.
Results
The T/B, SUVmax and expression of integrin αvβ3 in malignant lesions were higher than those in benign lesions (t = 3.691, P = 0.001; t = 8.271, P = 0.000; t = 3.632, P = 0.001, respectively). There was a significant correlation between T/B and SUVmax in esophageal lesions (r = 0.660, P = 0.000). The expression of integrin αvβ3 was correlated with [99mTc]3PRGD2 uptake (r = 0.782, P = 0.000). In visual analysis, the sensitivity and accuracy of the whole-body planar RGD scan were lower than those of the chest SPECT/CT RGD scan and the [18F]FDG PET/CT scan (x2 = 6.769, P = 0.022). The sensitivity, specificity and accuracy of the chest SPECT/CT RGD scan were similar to those of the [18F] FDG PET/CT scan. In semi-quantitative analysis, the sensitivity, specificity and accuracy of chest SPECT/CT RGD from the receiver operating characteristic (ROC) analysis were 87%, 100% and 94%, respectively [cutoff = 3.1 of T/B, area under the curve (AUC) = 0.957]. Thirteen patients (30 lymph nodes) and 16 patients (105 lymph nodes) were suspected to have lymph node metastases based on the RGD and FDG scans, respectively.
Conclusion
This prospective study demonstrated that [99mTc]3PRGD2 imaging is valuable for the diagnosis and staging of esophageal cancer. It may be less sensitive than [18F]FDG imaging for detecting metastatic lesions in small lymph nodes. The T/B value was correlated with the expression of integrin αvβ3.
NIH ClinicalTrials.gov
NCT 02744729.
Similar content being viewed by others
References
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.
Kim T, Grobmyer SR, Smith R, Ben-David K, Ang D, Vogel SB, et al. Esophageal cancer: the five year survivors. J Surg Oncol. 2011;103:179–83.
Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, et al. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011;29:868–74.
Okines AF, Reynolds AR, Cunningham D. Targeting angiogenesis in esophagogastric adenocarcinoma. Oncologist. 2011;16:844–58.
Pasini F, Fraccon AP, Modena Y, Bencivenga M, Giacopuzzi S, La Russa F, et al. Targeted therapies for advanced and metastatic adenocarcinoma of the gastroesophageal junction: is there something new? Gastric Cancer. 2017;20:31–42.
Beer AJ, Haubner R, Sarbia M, Goebel M, Luderschmidt S, Grosu AL, et al. Positron emission tomography using [18F] galacto-RGD identifies the level of integrin αvβ3 expression in man. Clin Cancer Res. 2006;12:3942–9.
Axelsson R, Bach-Gansmo T, Castell-Conesa J, McParland BJ, et al. An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the alpha v beta 3-selective angiogenesis imaging agent [99mTc]-NC100692. Acta Radiol. 2010;51:40–6.
Wang L, Shi J, Kim YS, Zhai S, Jia B, Zhao H, et al. Improving tumor-targeting capability and pharmacokinetics of 99mTc-labeled cyclic RGD dimers with PEG4 linkers. Mol Pharm. 2009;6:231–45.
Jia B, Liu Z, Zhu Z, Shi J, Jin X, Zhao H, et al. Blood clearance kinetics, biodistribution, and radiation dosimetry of a kit-formulate integrin αvβ3-selective radiotracer [99mTc]3PRGD2 in non-human primates. Mol Imaging Biol. 2011;13:730–6.
Zhu Z, Miao W, Li Q, Dai H, Ma Q, Wang F, et al. [99mTc]3PRGD2 for integrin receptor imaging of lung cancer: a multicenter study. J Nucl Med. 2012;53:716–22.
Miao W, Zheng S, Dai H, Wang F, Jin X, Zhu Z, et al. Comparison of [99mTc]3PRGD2 integrin receptor imaging with [99mTc]MDP bone scan in diagnosis of bone metastasis in patients with lung cancer: a multicenter study. PLoS One. 2014;9:e111221.
Chen Q, Xie Q, Zhao M, Chen B, Gao S, Zhang H, et al. Diagnostic value of [99mTc]3PRGD2 scintimammography for differentiation of malignant from benign breast lesions: comparison of visual and semi-quantitative analysis. Hell J Nucl Med. 2015;18:193–8.
Huang C, Zheng Q, Miao W. Study of novel molecular probe [99mTc]3PRGD2 in the diagnosis of rheumatoid arthritis. Nucl Med Commun. 2015;36:1208–14.
Liu Z, Jia B, Shi J, Jin X, Zhao H, Li F, et al. Tumor uptake of the RGD dimeric probe [99mTc]-G3-2P4-RGD2 is correlated with integrin expressed on both tumor cells and neovasculature. Bioconjug Chem. 2010;21:548–55.
Ma Q, Chen B, Gao S, Ji T, Wen Q, Song Y, et al. [99mTc]-3P4-RGD2 scintimammography in the assessment of breast lesions: comparative study with [99mTc] MIBI. PLoS One. 2014;9:e108349.
Zhao D, Jin X, Li F, Liang J, Lin Y, et al. Integrin αvβ3 imaging of radioactive iodine–refractory thyroid cancer using [99mTc]3PRGD2. J Nucl Med. 2012;53:1872–7.
Miller JC, Pien HH, Sahani D, Sorensen AG, Thrall JH. Imaging angiogenesis: applications and potential for drug development. J Natl Cancer Inst. 2005;97:172–87.
Cai W, Rao J, Gambhir SS, Chen X. How molecular imaging is speeding up antiangiogenic drug development. Mol Cancer Ther. 2006;5:2624–33.
Niu G, Chen X. Has molecular and cellular imaging enhanced drug discovery and drug development. Drugs R D. 2008;9:351–68.
Acknowledgements
We thank the Medical Isotopes Research Center of Peking University in China for the support with the 3PRGD2 kit.
Funding
This work was financially supported by the Science Foundation for Young Scientists of the Fujian Health and Family Planning Commission (2015-1-51).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Rights and permissions
About this article
Cite this article
Zheng, S., Chen, Z., Huang, C. et al. [99mTc]3PRGD2 for integrin receptor imaging of esophageal cancer: a comparative study with [18F]FDG PET/CT. Ann Nucl Med 33, 135–143 (2019). https://doi.org/10.1007/s12149-018-1315-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12149-018-1315-3