Annals of Nuclear Medicine

, Volume 33, Issue 1, pp 39–46 | Cite as

Advantages of 99mTc-3PRGD2 SPECT over CT in the preoperative assessment of lymph node metastasis in patients with esophageal cancer

  • Ningning Lv
  • Shi GaoEmail author
  • Lin Bai
  • Bin Ji
  • Jinru Xue
  • Xiaoguang Ge
  • Bin ChenEmail author
Original Article



Our study was designed to compare the diagnostic efficacies of integrated 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) single-photon emission computed tomography (SPECT) images and computed tomography (CT) images in lymph node metastasis in the patients with esophageal cancer.


From September 2015 and May 2018, 32 patients with histologically proven primary esophageal carcinoma underwent both 99mTc-3PRGD2 SPECT and CT scans followed by esophagectomy with lymph node dissection. The results of reviewing 99mTc-3PRGD2 SPECT and CT images for the lymph node metastasis were compared in relation with pathologic findings.


During surgery, a total of 168 lymph nodes were dissected in 32 patients, of which 42 node groups in 18 patients were malignant on histologic examination. Preoperative nodal staging was compared with postoperative histopathological staging, The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 99mTc-3PRGD2 SPECT for lymph nodes were 80.95%, 86.51%, 85.12%, 66.67%, and 93.16% on per-node basis, respectively; compared with 59.52%, 73.02%, 69.64%, 42.37%, and 84.40% for CT (p = 0.034, 0.008, 0.005, 0.011, and 0.038, respectively). 70.59% (12/17) false-negative interpretations and 50% (17/34) false-positive interpretations on CT were corrected by 99mTc-3PRGD2 SPECT. 37.5% false-negative interpretations on 99mTc-3PRGD2 SPECT were corrected by CT. 11.90% (5/42) positive lymph nodes and 13.49% (17/126) negative nodes at pathology were incorrectly diagnosed both by 99mTc-3PRGD2 SPECT and CT. The accuracy of 99mTc-3PRGD2 SPECT (87.50%, 28/32) was significantly higher than that of CT (62.50, 20/32; p = 0.022) on per-patient basis. 99mTc-3PRGD2 SPECT showed significantly higher sensitivity and accuracy in the neck and upper thoracic regions than CT. For nodal staging, 99mTc-3PRGD2 SPECT was correct in 78.12% (25/32) of the patients, whereas CT was correct in 53.12% (17/32), p = 0.037.


99mTc-3PRGD2 SPECT is more accurate than CT for preoperative assessment of lymph node metastasis in esophageal cancer and may be helpful in determining the therapeutic plan.


99mTc-3PRGD2 Esophageal cancer SPECT CT Lymph node 



This research was supported by the National Natural Science Foundation of China (NSFC) projects (Grant number: 81501506), the Foundation of National Health and Family Planning Commission of Jilin Province (Grant number: 2016Q038), the Norman Bethune Program of Jilin University (Grant number: 2015219).

Compliance with ethical standards

Conflict of interest

The author declares that they have no conflict of interest.


  1. 1.
    Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. Ca Cancer J Clin. 2016;66(2):115–32.CrossRefGoogle Scholar
  2. 2.
    Eloubeidi MA, Desmond R, Arguedas MR, Reed CE, Wilcox CM. Prognostic factors for the survival of patients with esophageal carcinoma in the U.S.: the importance of tumor length and lymph node status. Cancer. 2002;95(7):1434–43.CrossRefGoogle Scholar
  3. 3.
    Mariette C, Piessen G, Briez N, Triboulet JP. The number of metastatic lymph nodes and the ratio between metastatic and examined lymph nodes are independent prognostic factors in esophageal cancer regardless of neoadjuvant chemoradiation or lymphadenectomy extent. Ann Surg. 2008;247(2):365–71.CrossRefGoogle Scholar
  4. 4.
    Tachimori Y, Ozawa S, Numasaki H, Ishihara R, Matsubara H, Muro K, et al. Comprehensive registry of esophageal cancer in Japan, 2011. Esophagus. 2018;15(3):127–52.CrossRefGoogle Scholar
  5. 5.
    Vilgrain V, Mompoint D, Palazzo L, Menu Y, Gayet B, Ollier P, et al. Staging of esophageal carcinoma: comparison of results with endoscopic sonography and CT. Ajr Am J Roentgenol. 1990;155(2):277–81.CrossRefGoogle Scholar
  6. 6.
    Goei R, Lamers RJ, Engelshove HA, Oei KT. Computed tomographic staging of esophageal carcinoma: a study on interobserver variation and correlation with pathological findings. Eur J Radiol. 1992;15(15):40–4.CrossRefGoogle Scholar
  7. 7.
    Tio TL, Coene PP, Schouwink MH, Tytgat GN. Esophagogastric carcinoma: preoperative TNM classification with endosonography. Radiology. 1989;173(2):411–7.CrossRefGoogle Scholar
  8. 8.
    Zhang X, Watson DI, Lally C, Bessell JR. Endoscopic ultrasound for preoperative staging of esophageal carcinoma. Surg Endosc. 2005;19(12):1618–21.CrossRefGoogle Scholar
  9. 9.
    Tsai JA, Celebioglu F, Lindblad M, Lörinc E, Nilsson M, Olsson A, et al. Hybrid SPECT/CT imaging of sentinel nodes in esophageal cancer: first results. Acta Radiol. 2013;54(4):369–73.CrossRefGoogle Scholar
  10. 10.
    Ayala-Peacock DN, Thomas AJ, Smith H, Garg P, Blackstock AW. A Pilot 11C-choline PET-CT imaging study in patients with locally advanced esophageal cancer. Pract Radiat Oncol. 2013;3(2 Suppl 1):23.CrossRefGoogle Scholar
  11. 11.
    Cremonesi M, Garibaldi C, Timmerman R, Ferrari M, Ronchi S, Grana CM, et al. Interim 18F-FDG-PET/CT during chemo-radiotherapy in the management of oesophageal cancer patients. Radiother Oncol. 2017;125(2):200–12.CrossRefGoogle Scholar
  12. 12.
    Gang N, Chen X. Why integrin as a primary target for imaging and therapy. Theranostics. 2011;1(1):30–47.Google Scholar
  13. 13.
    GAO Shi MA, Qingjie WEN, Qiang JIA, Bing LIU, Zhaofei CHEN, Zuowei, et al. ~(99 m)Tc-3P_4—RGD_2 radiotracers for SPECT/CT of esophageal tumor. Nucl Sci Tech. 2013;24(4):38–43.Google Scholar
  14. 14.
    Jin X, Liang N, Wang M, Meng Y, Jia B, Shi X, et al. Integrin Imaging with 99 m Tc-3PRGD2 SPECT/CT shows high specificity in the diagnosis of lymph node metastasis from non-small cell lung cancer. Radiology. 2016;281(3):958–66.CrossRefGoogle Scholar
  15. 15.
    Sobin LH, Gospodarowicz M. TNM classification of malignant tumours. John Wiley & Sons: New York, USA; 2009.Google Scholar
  16. 16.
    Guanghui C, Shi G, Tiefeng J, Qingjie M, Bing j, Zhuowei C, et al. Pharmacokinetics and radiation dosimetry of, (99 m) Tc-3PRGD_2 in healthy individuals: A pilot study. Nucl Sci Tech. 2012;23(6):349–54.Google Scholar
  17. 17.
    Korst RJ, Rusch VW, Venkatraman E, Bains MS, Burt ME, Downey RJ, et al. Proposed revision of the staging classification for esophageal cancer. J Thorac Cardiovasc Surg. 1998;115(3):660–9.CrossRefGoogle Scholar
  18. 18.
    Lerut T, Coosemans W, Decker G, De Leyn P, Nafteux P, Van Raemdonck D. Cancer of the esophagus and gastro-esophageal junction: potentially curative therapies. Surg Oncol. 2001;10(3):113–22.CrossRefGoogle Scholar
  19. 19.
    Stacker SA, Williams SP, Karnezis T, Shayan R, Fox SB, Achen MG. Lymphangiogenesis and lymphatic vessel remodelling in cancer. Nat Rev Cancer. 2014;14(3):159–72.CrossRefGoogle Scholar
  20. 20.
    Ma Q, Ji B, Jia B, Gao S, Ji T, Wang X, et al. Differential diagnosis of solitary pulmonary nodules using 99mTc-3P4-RGD2 scintigraphy. Eur J Nucl Med Mol Imaging. 2011;38(12):2145–52.CrossRefGoogle Scholar
  21. 21.
    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(9):e108349.CrossRefGoogle Scholar
  22. 22.
    Liu L, Song Y, Gao S, Ji T, Zhang H, Ji B, et al. (99)mTc-3PRGD2 scintimammography in palpable and nonpalpable breast lesions. Mol Imaging. 2013;13(5):1–7.Google Scholar
  23. 23.
    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(5):716–22.CrossRefGoogle Scholar
  24. 24.
    Ma Q, Min K, Wang T, Chen B, Wen Q, Wang F, et al. (99 m)Tc-3PRGD 2 SPECT/CT predicts the outcome of advanced nonsquamous non-small cell lung cancer receiving chemoradiotherapy plus bevacizumab. Ann Nucl Med. 2015;29(6):519–27.CrossRefGoogle Scholar
  25. 25.
    Kato H, Kimura H, Nakajima M, Sakai M, Sano A, Tanaka N, et al. The additional value of integrated PET/CT over PET in initial lymph node staging of esophageal cancer. Oncol Rep. 2008;20(4):857–62.Google Scholar
  26. 26.
    Kato H, Kuwano H, Nakajima M, Miyazaki T, Yoshikawa M, Ojima H, et al. Comparison between positron emission tomography and computed tomography in the use of the assessment of esophageal carcinoma. Cancer. 2002;94(4):921–8.CrossRefGoogle Scholar
  27. 27.
    Horton MA. The alpha v beta 3 integrin “vitronectin receptor”. Int J Biochem Cell Biol. 1997;29(5):721–5.CrossRefGoogle Scholar

Copyright information

© The Japanese Society of Nuclear Medicine 2018

Authors and Affiliations

  1. 1.Department of Nuclear MedicineChina-Japan Union Hospital of Jilin UniversityChangchunChina
  2. 2.Department of Thoracic SurgeryChina-Japan Union Hospital of Jilin UniversityChangchunChina

Personalised recommendations