Prognostic value of 99mTc-HYNIC Annexin-V imaging in squamous cell carcinoma of the head and neck

  • David Loose
  • Hubert Vermeersch
  • Filip De Vos
  • Philippe Deron
  • Guido Slegers
  • Christophe Van de Wiele
Original article

Abstract

Purpose

The purpose of the study was to report on the prognostic value of 99mTc-hydrazinonicotinamide (HYNIC) Annexin-V single-photon emission computed tomography (SPECT) imaging in patients suffering from primary squamous cell carcinoma of the head and neck.

Methods

Twenty-nine patients diagnosed with a primary untreated head and neck squamous cell carcinoma were included in this study. In all patients, 99mTc-HYNIC Annexin-V scintigraphy SPECT was performed before treatment instigation. Tumour-to-background ratios (T/N) of the primary tumour, derived from reconstructed images, as well as clinical variables were obtained in all patients and related to patient outcome. Median follow-up was 22.6 months (range 4.1–55.8 months).

Results

On univariate as well as multivariate analysis, only the 99mTc-HYNIC Annexin-V T/N ratio dichotomized using the group median as cutoff value (T/N ratio of 2) was predictive of recurrence-free survival (respectively, p = 0.0000 and 0.000). On univariate analysis, only lymph node status dichotomized according to N0 vs N1–N2–N3 disease and the 99mTc-HYNIC Annexin-V T/N ratio dichotomized using the group median as cutoff value (T/N ratio of 2) were predictive of overall survival (p = 0.0051 and 0.0000). When both factors were included in the multivariate model, both N status and the 99mTc-HYNIC Annexin-V T/N ratio showed an independent association with overall survival (p = 0.001 for lymph node status and 0.000 for dichotomized 99mTc-HYNIC Annexin-V T/N ratio).

Conclusion

99mTc-HYNIC Annexin-V T/N ratios derived from SPECT provides independent prognostic information on disease-free survival and overall survival.

Keywords

Annexin V Apoptosis imaging Molecular imaging Oncology Prognosis 

References

  1. 1.
    Parkin D, Läärä E, Muir C. Estimates of the worldwide frequency of sixteen major cancers in 1980. Int J Cancer 1988;41:184–97.PubMedCrossRefGoogle Scholar
  2. 2.
    Chin D, Boyle G, Porceddu S, Theik D, Parsons P, Coman W. Head and neck cancer: past, present and future. Expert Rev Anticancer Ther 2006;6:1111–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Stoll C, Baretton G, Ahrens C, Lohrs U. Prognostic significance of apoptosis and associated factors in oral squamous cell carcinoma. Virchows Arch 2000;436:102–8.PubMedCrossRefGoogle Scholar
  4. 4.
    van Engeland M, Nieland L, Ramaekers F, Schutte B, Reutelingsperger C. Annexin-V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry 1998;31:1–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Narula J, Acio ER, Narula N, Samuels L, Fyfe B, Wood D, et al. Annexin-V imaging for noninvasive detection of cardiac allograft rejection. Nature Med 2001;7:1347–52.PubMedCrossRefGoogle Scholar
  6. 6.
    Hofstra L, Liem I, Dumont EA, Boersma H, van Heerde W, Doevendans P, et al. Visualization of cell death in vivo in patients with acute myocardial infarction. Lancet 2000;356:209–12.PubMedCrossRefGoogle Scholar
  7. 7.
    Blankenberg F, Vriens P, Tait J. Non-invasive detection and quantification of acute heart transplant rejection using 99mTc radiolabeled annexin V. Radiology 1998;103 (abstr 1337).Google Scholar
  8. 8.
    Narula J, Acia E, Narula N. Phase-I Tc99m-Annexin-V imaging study in heart transplant rejection: can noninvasive detection of apoptosis in cardiac allografts obviate the need for endomyocardial biopsy. Circulation 2000;102 (abstr 3714).Google Scholar
  9. 9.
    Van de Wiele C, Lahorte C, Vermeersch H, Loose D, Mervillie K, Steinmetz N, et al. Quantitative tumor apoptosis imaging using 99mTc-HYNIC Annexin single photon emission computerized tomography. J Clin Oncol 2003;21:3483–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Vermeersch H, Ham H, Rottey S, Lahorte C, Corsetti F, Dierckx R, et al. Intra-observer, inter-observer and day-to-day reproducibility of quantitative 99mTc-HYNIC Annexin V imaging in head and neck carcinoma. Cancer Biother Radiopharm 2004;2:205–10.CrossRefGoogle Scholar
  11. 11.
    Rottey S, Slegers G, Van Belle S, Goethals I, Van de Wiele C. Sequential 99mTc-hydrazinonicotinamide-annexin V imaging for predicting response to chemotherapy. J Nucl Med 2006;47:1813–8.PubMedGoogle Scholar
  12. 12.
    Hall P. Assessing apoptosis: a critical survey. Endocr-Relat Cancer 1999;6:3–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Mundle S, Gao X, Khan S, Gregory S, Preisler H, Razza A. Two in situ end labeling techniques reveal different patterns of DNA fragmentation during spontaneous apoptosis in vivo and induced apoptosis in vitro. Anticancer Res 1995;15:1895–904.PubMedGoogle Scholar
  14. 14.
    Hotz M, Bosq J, Zbaeren P, Reed J, Schwab G, Krajewski S, et al. Spontaneous apoptosis and the expression of p53 and Bcl-2 family proteins in locally advanced head and neck cancer. Arch Otolaryngol Head Neck Surg 1999;125:417–22.PubMedGoogle Scholar
  15. 15.
    Naresh K, Lakshminarayanan K, Pai S, Borges A. Apoptosis index is a predictor of metastatic phenotype in patients with early stage squamous carcinoma of the tongue. Cancer 2001;91:578–84.PubMedCrossRefGoogle Scholar
  16. 16.
    Xie X, De Angelis P, Clausen O, Boysen M. Prognostic significance of proliferative and apoptotic markers in oral tongue squamous cell carcinomas. Oral Oncol 1999;35:502–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Hirvikoski P, Virtaniemi J, Kumpulainen E, Johansson R, Kosma V. Supraglottic and glottic carcinomas: clinically and biologically distinct entities. Eur J Cancer 2002;38:1717–23.PubMedCrossRefGoogle Scholar
  18. 18.
    Teppo H, Soini Y, Melkko J, Koivunen P, Alho P. Prognostic factors in laryngeal carcinoma: the role of apoptosis, p53, proliferation (Ki-67) and angiogenesis. APMIS 2003;111:451–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Jäckel M, Dorudian M, Marx D, Brinck U, Schauer A, Steiner W. Spontaneous apoptosis in laryngeal squamous cell carcinoma is independent of bcl-2 and bax protein expression. Cancer 1999;85:591–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Gastman B. Apoptosis and its clinical impact. Head Neck 2001;23:409–25.PubMedCrossRefGoogle Scholar
  21. 21.
    Gastman B, Atarshi Y, Reichert T, Saito T, Balkir L, Rabinowich H, et al. Fas ligand is expressed on human squamous cell carcinomas of the head and neck, and it promotes apoptosis of T lymphocytes. Cancer Res 1991;59:5356–64.Google Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • David Loose
    • 1
  • Hubert Vermeersch
    • 1
  • Filip De Vos
    • 2
  • Philippe Deron
    • 1
  • Guido Slegers
    • 2
  • Christophe Van de Wiele
    • 3
    • 4
    • 5
  1. 1.Department of Head and Neck SurgeryUniversity Hospital GhentGhentBelgium
  2. 2.Department of RadiopharmacyUniversity Hospital GhentGhentBelgium
  3. 3.Department of Nuclear MedicineUniversity Hospital GhentGhentBelgium
  4. 4.Department of Experimental CancerologyUniversity Hospital GhentGhentBelgium
  5. 5.Department of RadiotherapyUniversity Hospital GhentGhentBelgium

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