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Relationship Between Clinicopathological Characteristics and PET/CT Uptake in Esophageal Squamous Cell Carcinoma: [18F]Alfatide versus [18F]FDG

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Abstract

Purpose

To assess a novel radiotracer aluminum [18F]fluoride-1,4,7-triazacyclononane-triacetic acid-pegylated dimeric RGD ([18F]ALF-NOTA-PRGD2, denoted as [18F]Alfatide) for positron emission tomography (PET)/X-ray computed tomography (CT) and explore the relationships between clinicopathological characteristics and maximum standard uptake values in primary (SUVP) and metastatic lymph nodes (SUVLN) of patients with esophageal squamous cell carcinoma (ESCC), as verified by pathologic examination and compared with those obtained with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]DG) PET.

Procedures

We prospectively enrolled patients with newly diagnosed ESCC who agreed to undergo [18F]Alfatide PET/CT or [18F]FDG PET/CT scans before surgery at Shandong Cancer Hospital from May 2011 to July 2017. SUVs and the pathological tumor-node-metastasis (pTNM) stages of primary tumors and metastatic lymph nodes (LNs) were measured and confirmed pathologically. Immunohistochemical (IHC) staining for integrin αvβ3 was performed on tumor samples (both primary tumors and metastatic LNs) collected from nine patients.

Results

Of 61 patients who underwent PET/CT scans, 46 then underwent curative surgery and were included in our analysis (n = 21 for [18F]Alfatide PET/CT and n = 25 for [18F]FDG PET/CT). No significant differences in the SUVP on [18F]Alfatide PET/CT or [18F]FDG PET/CT were observed among the cohorts according to gender, pathological stage, T stage, status of LNs, and differentiation (all P > 0.05). The SUVLN differed significantly between the pathological stages and status of LNs both on [18F]Alfatide PET/CT (P = 0.03, 0.003) and [18F]FDG PET/CT (P = 0.001. < 0.001), but not according to gender (P = 0.128, 0.129), T stage (P = 0.791, 0.727), or tumor differentiation (P = 0.049, 0.053). Significant positive correlations were observed between the SUVLN on [18F]Alfatide PET/CT and [18F]FDG PET/CT, and pathological stage (r = 0.52, P = 0.016; r = 0.503, P = 0.01), LN status (r = 0.73, P < 0.001; r = 0.649, P < 0.001), and differentiation (r = 0.509, P < 0.019; r = 0.459, P = 0.021) were observed. No significant differences were found between the relationships of SUVP with SUVLN, length, age, gender, pathological stage, T stage, status of LN, or differentiation, or of SUVLN with length, age, gender, or T stage both on [18F]Alfatide PET/CT and [18F]FDG PET/CT (all P > 0.05). The quantitated expression levels of αvβ3 in primary tumors and metastatic LNs were 1.67 ± 1.12 and 3.42 ± 2.93, respectively (P = 0.031).

Conclusions

Our results suggest that SUVLN is influenced by pathological stage, LN status, and differentiation. SUVLN may therefore serve as a new parameter for risk stratification of with ESCC patients. Moreover, [18F]Alfatide PET can provide complementary molecular information about ESCC metastasis.

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References

  1. Czernin J, Phelps ME (2002) Positron emission tomography scanning: current and future applications. Annu Rev Med 53:89–112

    Article  CAS  PubMed  Google Scholar 

  2. Phay JE, Hussain HB, Moley JF (2000) Strategy for identification of novel glucose transporter family members by using internet-based genomic databases. Surgery 128:946–951

    Article  CAS  PubMed  Google Scholar 

  3. Flamen P, Lerut A, Van Cutsem E et al (2000) Utility of positron emission tomography for the staging of patients with potentially operable esophageal carcinoma. J Clin Oncol 18:3202–3210

    Article  CAS  PubMed  Google Scholar 

  4. Heeren PA, Jager PL, Bongaerts F, van Dullemen H, Sluiter W, Plukker JT (2004) Detection of distant metastases in esophageal cancer with 18F-FDG PET. J Nucl Med 45:980–987

    PubMed  Google Scholar 

  5. Strauss LG (1996) Fluorine-18 deoxyglucose and false-positive results: a major problem in the diagnostics of oncological patients. Eur J Nucl Med 23:1409–1415

    Article  CAS  PubMed  Google Scholar 

  6. van Westreenen HL, Heeren PA, Jager PL et al (2003) Pitfalls of positive findings in staging esophageal cancer with F-18-fluorodeoxyglucose positron emission tomography. Ann Surg Oncol 10:1100–1105

    Article  PubMed  Google Scholar 

  7. Ishimori T, Saga T, Mamede M, Kobayashi H, Higashi T, Nakamoto Y, Sato N, Konishi J (2002) Increased (18)F-FDG uptake in a model of inflammation: concanavalin A-mediated lymphocyte activation. J Nucl Med 43:658–663

    CAS  PubMed  Google Scholar 

  8. Kubota R, Yamada S, Kubota K, Ishiwata K, Tamahashi N, Ido T (1992) Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med 33:1972–1980

    CAS  PubMed  Google Scholar 

  9. Hood JD, Cheresh DA (2002) Role of integrins in cell invasion and migration. Nat Rev Cancer 2:91–100

    Article  PubMed  Google Scholar 

  10. Wu C, Yue X, Lang L, Kiesewetter DO, Li F, Zhu Z, Niu G, Chen X (2014) Longitudinal PET imaging of muscular inflammation using 18F-DPA-714 and 18F-Alfatide II and differentiation with tumors. Theranostics 4:546–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gao S, Wu H, Li W, Zhao S, Teng X, Lu H, Hu X, Wang S, Yu J, Yuan S (2015) A pilot study imaging integrin αvβ3 with RGD PET/CT in suspected lung cancer patients. Eur J Nucl Med Mol Imaging 42:2029–2037

    Article  CAS  PubMed  Google Scholar 

  12. Luan X, Huang Y, Gao S, Sun X, Wang S, Ma L, Teng X, Lu H, Yu J, Yuan S (2016) 18 F-alfatide PET/CT may predict short-term outcome of concurrent chemoradiotherapy in patients with advanced non-small cell lung cancer. Eur J Nucl Med Mol Imaging 43:2336–2342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zhang H, Liu N, Gao S, Hu X, Zhao W, Tao R, Chen Z, Zheng J, Sun X, Xu L, Li W, Yu J, Yuan S (2016) Can an 18F-ALF-NOTA-PRGD2 PET/CT scan predict treatment sensitivity to concurrent chemoradiotherapy in patients with newly diagnosed glioblastoma. J Nucl Med 57:524–529

    Article  CAS  PubMed  Google Scholar 

  14. Wan W, Guo N, Pan D, Yu C, Weng Y, Luo S, Ding H, Xu Y, Wang L, Lang L, Xie Q, Yang M, Chen X (2013) First experience of 18F-alfatide in lung cancer patients using a new lyophilized kit for rapid radiofluorination. J Nucl Med 54:691–698

    Article  CAS  PubMed  Google Scholar 

  15. Beer AJ, Haubner R, Sarbia M, Goebel M, Luderschmidt S, Grosu AL, Schnell O, Niemeyer M, Kessler H, Wester HJ, Weber WA, Schwaiger M (2006) Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin alpha(v)beta3 expression in man. Clin Cancer Res 12:3942–3949

    Article  CAS  PubMed  Google Scholar 

  16. Chen X, Sievers E, Hou Y, Park R, Tohme M, Bart R, Bremner R, Bading JR, Conti PS (2005) Integrin alpha v beta 3-targeted imaging of lung cancer. Neoplasia 7:271–279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Thurau K, Palmes D, Franzius C, Minin E, Senninger N, Juergens KU, Bruewer M (2011) Impact of PET-CT on primary staging and response control on multimodal treatment of esophageal cancer. World J Surg 35:608–616

    Article  PubMed  Google Scholar 

  18. Suzuki A, Xiao L, Hayashi Y, Macapinlac HA, Welsh J, Lin SH, Lee JH, Bhutani MS, Maru DM, Hofstetter WL, Swisher SG, Ajani JA (2011) Prognostic significance of baseline positron emission tomography and importance of clinical complete response in patients with esophageal or gastroesophageal junction cancer treated with definitive chemoradiotherapy. Cancer 117:4823–4833

    Article  PubMed  Google Scholar 

  19. Cerfolio RJ, Bryant AS (2006) Maximum standardized uptake values on positron emission tomography of esophageal cancer predicts stage, tumor biology, and survival. Ann Thorac Surg 82:391–394; discussion 394-395

    Article  PubMed  Google Scholar 

  20. Rizk N, Downey RJ, Akhurst T, Gonen M, Bains MS, Larson S, Rusch V (2006) Preoperative 18F-fluorodeoxyglucose positron emission tomography standardized uptake values predict survival after esophageal adenocarcinoma resection. Ann Thorac Surg 81:1076–1081

    Article  PubMed  Google Scholar 

  21. Vesselle H, Schmidt RA, Pugsley JM, Li M, Kohlmyer SG, Vallires E, Wood DE (2000) Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography. Clin Cancer Res 6:3837–3844

    CAS  PubMed  Google Scholar 

  22. Feng R, Li MH, Kong L, Shi F, Yang GR, Yu JM (2009) Correlation between PET-CT 18FDG uptake in primary lesions and clinicopathological parameters in esophageal carcinoma patients. Zhonghua Zhong Liu Za Zhi 31:452–454

    CAS  PubMed  Google Scholar 

  23. Mu DB, Wang SP, Yang WF et al (2007) Correlation between FDG PET/CT and the expression of glutl and ki-67 antigen in esophageal cancer. Zhonghua Zhong Liu Za Zhi 29:30–33

    CAS  PubMed  Google Scholar 

  24. Wu C, Yue X, Lang L, Kiesewetter DO, Li F, Zhu Z, Niu G, Chen X (2014) Longitudinal PET imaging of muscular inflammation using 18F-DPA-714 and 18F-Alfatide II and differentiation with tumors. Theranostics 4:546–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hynes RO (2002) A reevaluation of integrins as regulators of angiogenesis. Nat Med 8:918–921

    Article  CAS  PubMed  Google Scholar 

  26. Sun M, Li B, Fu Z et al (2013) Relationship between 18F-fluorodeoxyglucose uptake in primary lesions and clinicopathological characteristics of esophageal squamous cell carcinoma patients. Exp Ther Med 5:170–174

    Article  PubMed  Google Scholar 

  27. Liu H, Lu L, Zhu Q, Hao YT, Mo YX, Liu M, Hu YH, Cui NJ, Rong TH (2011) Cervical nodal metastases of unresectable thoracic esophageal squamous cell carcinoma: characteristics of long-term survivors after concurrent chemoradiotherapy. Radiother Oncol 99:181–186

    Article  PubMed  Google Scholar 

  28. Eloubeidi MA, Desmond R, Arguedas MR, Reed CE, Wilcox CM (2002) Prognostic factors for the survival of patients with esophageal carcinoma in the U.S.: the importance of tumor length and lymph node status. Cancer 95:1434–1443

    Article  PubMed  Google Scholar 

  29. Roedl JB, Sahani DV, Colen RR, Fischman AJ, Mueller PR, Blake MA (2008) Tumour length measured on PET-CT predicts the most appropriate stage-dependent therapeutic approach in oesophageal cancer. Eur Radiol 18:2833–2840

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors extend their gratitude to Professor Yongsheng Gao (Department of Pathology, Shandong Cancer Hospital and Institute) for his help with IHC analysis and Jianbo Zhang (Department of Pathology, Shandong Cancer Hospital and Institute) for his help with the IHC examination.

Funding

This study was partially funded by the Special Fund for Scientific Research in the Public Interest (201402011), the National Key Research and Development Plan (2016YFC0904700), the Natural Science Foundation of China (NSFC81172133, NSFC81372413), the Shandong Key Research and Development Plan (2017CXGC1209 and 2017GSF18164), and the Outstanding Youth Natural Science Foundation of Shandong Province (JQ201423).

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Correspondence to Shuanghu Yuan.

Ethics declarations

This study was approved by the ethics committee of Shandong Cancer Hospital, and each patient provided written informed consent prior to the study.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Dong, Y., Wei, Y., Chen, G. et al. Relationship Between Clinicopathological Characteristics and PET/CT Uptake in Esophageal Squamous Cell Carcinoma: [18F]Alfatide versus [18F]FDG. Mol Imaging Biol 21, 175–182 (2019). https://doi.org/10.1007/s11307-018-1216-9

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