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Published in: European Journal of Nuclear Medicine and Molecular Imaging 3/2008

Open Access 01-03-2008 | Original Article

99mTc Hynic-rh-Annexin V scintigraphy for in vivo imaging of apoptosis in patients with head and neck cancer treated with chemoradiotherapy

Authors: Frank J. P. Hoebers, Marina Kartachova, Josien de Bois, Michiel W. M. van den Brekel, Harm van Tinteren, Marcel van Herk, Coen R. N. Rasch, Renato A. Valdés Olmos, Marcel Verheij

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 3/2008

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Abstract

Purpose

The purpose of this study was to determine the value of 99mTc Hynic-rh-Annexin-V-Scintigraphy (TAVS), a non-invasive in vivo technique to demonstrate apoptosis in patients with head and neck squamous cell carcinoma.

Methods

TAVS were performed before and within 48 h after the first course of cisplatin-based chemoradiation. Radiation dose given to the tumour at the time of post-treatment TAVS was 6–8 Gy. Single-photon emission tomography data were co-registered to planning CT scan. Complete sets of these data were available for 13 patients. The radiation dose at post-treatment TAVS was calculated for several regions of interest (ROI): primary tumour, involved lymph nodes and salivary glands. Annexin uptake was determined in each ROI, and the difference between post-treatment and baseline TAVS represented the absolute Annexin uptake: Delta uptake (ΔU).

Results

In 24 of 26 parotid glands, treatment-induced Annexin uptake was observed. Mean ΔU was significantly correlated with the mean radiation dose given to the parotid glands (r = 0.59, p = 0.002): Glands that received higher doses showed more Annexin uptake. ΔU in primary tumour and pathological lymph nodes showed large inter-patient differences. A high correlation was observed on an inter-patient level (r = 0.71, p = 0.006) between the maximum ΔU in primary tumour and in the lymph nodes.

Conclusions

Within the dose range of 0–8 Gy, Annexin-V-scintigraphy showed a radiation-dose-dependent uptake in parotid glands, indicative of early apoptosis during treatment. The inter-individual spread in Annexin uptake in primary tumours could not be related to differences in dose or tumour volume, but the Annexin uptake in tumour and lymph nodes were closely correlated. This effect might represent a tumour-specific apoptotic response.
Literature
1.
go back to reference Dive C, Evans CA, Whetton AD. Induction of apoptosis-new targets for cancer chemotherapy. Semin Cancer Biol 1992;3:417–27.PubMed Dive C, Evans CA, Whetton AD. Induction of apoptosis-new targets for cancer chemotherapy. Semin Cancer Biol 1992;3:417–27.PubMed
2.
4.
go back to reference Tamm I, Schriever F, Dorken B. Apoptosis: implications of basic research for clinical oncology. Lancet Oncol 2001;2:33–42.PubMedCrossRef Tamm I, Schriever F, Dorken B. Apoptosis: implications of basic research for clinical oncology. Lancet Oncol 2001;2:33–42.PubMedCrossRef
5.
go back to reference Meyn RE, Stephens LC, Milas L. Programmed cell death and radioresistance. Cancer Metastasis Rev 1996;15:119–31.PubMedCrossRef Meyn RE, Stephens LC, Milas L. Programmed cell death and radioresistance. Cancer Metastasis Rev 1996;15:119–31.PubMedCrossRef
6.
go back to reference Blankenberg FG, Katsikis PD, Tait JF, Davis RE, Naumovski L, Ohtsuki K, et al. In vivo detection and imaging of phosphatidylserine expression during programmed cell death. Proc Natl Acad Sci USA 1998;95:6349–54.PubMedCrossRef Blankenberg FG, Katsikis PD, Tait JF, Davis RE, Naumovski L, Ohtsuki K, et al. In vivo detection and imaging of phosphatidylserine expression during programmed cell death. Proc Natl Acad Sci USA 1998;95:6349–54.PubMedCrossRef
7.
go back to reference Kemerink GJ, Liu X, Kieffer D, Ceyssens S, Mortelmans L, Verbruggen AM, et al. Safety, biodistribution, and dosimetry of 99mTc-HYNIC-annexin V, a novel human recombinant annexin V for human application. J Nucl Med 2003;44:947–52.PubMed Kemerink GJ, Liu X, Kieffer D, Ceyssens S, Mortelmans L, Verbruggen AM, et al. Safety, biodistribution, and dosimetry of 99mTc-HYNIC-annexin V, a novel human recombinant annexin V for human application. J Nucl Med 2003;44:947–52.PubMed
8.
go back to reference Van De Wiele C, Lahorte C, Vermeersch H, Loose D, Mervillie K, Steinmetz ND, et al. Quantitative tumor apoptosis imaging using technetium-99m-HYNIC annexin V single photon emission computed tomography. J Clin Oncol 2003;21:3483–7.PubMedCrossRef Van De Wiele C, Lahorte C, Vermeersch H, Loose D, Mervillie K, Steinmetz ND, et al. Quantitative tumor apoptosis imaging using technetium-99m-HYNIC annexin V single photon emission computed tomography. J Clin Oncol 2003;21:3483–7.PubMedCrossRef
9.
go back to reference Kuge Y, Sato M, Zhao S, Takei T, Nakada K, Seki KI, et al. Feasibility of 99mTc-annexin V for repetitive detection of apoptotic tumor response to chemotherapy: an experimental study using a rat tumor model. J Nucl Med 2004;45:309–12.PubMed Kuge Y, Sato M, Zhao S, Takei T, Nakada K, Seki KI, et al. Feasibility of 99mTc-annexin V for repetitive detection of apoptotic tumor response to chemotherapy: an experimental study using a rat tumor model. J Nucl Med 2004;45:309–12.PubMed
10.
go back to reference Ogura Y, Krams SM, Martinez OM, Kopiwoda S, Higgins JP, Esquivel CO, et al. Radiolabeled annexin V imaging: diagnosis of allograft rejection in an experimental rodent model of liver transplantation. Radiology 2000;214:795–800.PubMed Ogura Y, Krams SM, Martinez OM, Kopiwoda S, Higgins JP, Esquivel CO, et al. Radiolabeled annexin V imaging: diagnosis of allograft rejection in an experimental rodent model of liver transplantation. Radiology 2000;214:795–800.PubMed
11.
go back to reference Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol 1992;148:2207–16.PubMed Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol 1992;148:2207–16.PubMed
12.
go back to reference van Engeland M, Kuijpers HJ, Ramaekers FC, Reutelingsperger CP, Schutte B. Plasma membrane alterations and cytoskeletal changes in apoptosis. Exp Cell Res 1997;235:421–30.PubMedCrossRef van Engeland M, Kuijpers HJ, Ramaekers FC, Reutelingsperger CP, Schutte B. Plasma membrane alterations and cytoskeletal changes in apoptosis. Exp Cell Res 1997;235:421–30.PubMedCrossRef
13.
go back to reference Vermeersch H, Ham H, Rottey S, Lahorte C, Corsetti F, Dierckx R, et al. Intraobserver, interobserver, and day-to-day reproducibility of quantitative 99mTc-HYNIC annexin-V imaging in head and neck carcinoma. Cancer Biother Radiopharm 2004;19:205–10.PubMedCrossRef Vermeersch H, Ham H, Rottey S, Lahorte C, Corsetti F, Dierckx R, et al. Intraobserver, interobserver, and day-to-day reproducibility of quantitative 99mTc-HYNIC annexin-V imaging in head and neck carcinoma. Cancer Biother Radiopharm 2004;19:205–10.PubMedCrossRef
14.
go back to reference Haas RL, de Jong D, Valdes Olmos RA, Hoefnagel CA, Van Den Heuvel I, Zerp SF, et al. In vivo imaging of radiation-induced apoptosis in follicular lymphoma patients. Int J Radiat Oncol Biol Phys 2004;59:782–7.PubMed Haas RL, de Jong D, Valdes Olmos RA, Hoefnagel CA, Van Den Heuvel I, Zerp SF, et al. In vivo imaging of radiation-induced apoptosis in follicular lymphoma patients. Int J Radiat Oncol Biol Phys 2004;59:782–7.PubMed
15.
go back to reference Kartachova M, Haas RL, Valdes Olmos RA, Hoebers FJ, van Zandwijk N, Verheij M. In vivo imaging of apoptosis by (99m)Tc-Annexin V scintigraphy: visual analysis in relation to treatment response. Radiother Oncol 2004;72:333–9.PubMedCrossRef Kartachova M, Haas RL, Valdes Olmos RA, Hoebers FJ, van Zandwijk N, Verheij M. In vivo imaging of apoptosis by (99m)Tc-Annexin V scintigraphy: visual analysis in relation to treatment response. Radiother Oncol 2004;72:333–9.PubMedCrossRef
16.
go back to reference Pignon JP, Bourhis J, Domenge C, Designe L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-analysis of chemotherapy on head and neck cancer. Lancet 2000;355:949–55.PubMed Pignon JP, Bourhis J, Domenge C, Designe L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-analysis of chemotherapy on head and neck cancer. Lancet 2000;355:949–55.PubMed
17.
go back to reference Bourhis J. and C.Amand, J.-P. Pignon on behalf of the MACH-NC Collaborative Group. Update of MACH-NC (meta-analysis of chemotherapy in head & neck cancer) database focused on concomitant chemoradiotherapy. Journal of Clinical Oncology 22 No 14S (July 15 Supplement). ASCO Annual Meeting Proceedings (Post-Meeting Edition) 2004; p. 5505. Bourhis J. and C.Amand, J.-P. Pignon on behalf of the MACH-NC Collaborative Group. Update of MACH-NC (meta-analysis of chemotherapy in head & neck cancer) database focused on concomitant chemoradiotherapy. Journal of Clinical Oncology 22 No 14S (July 15 Supplement). ASCO Annual Meeting Proceedings (Post-Meeting Edition) 2004; p. 5505.
18.
go back to reference Balm AJ, Rasch CR, Schornagel JH, Hilgers FJ, Keus RB, Schultze-Kool L, et al. High-dose superselective intra-arterial cisplatin and concomitant radiation (RADPLAT) for advanced head and neck cancer. Head Neck 2004;26:485–93.PubMedCrossRef Balm AJ, Rasch CR, Schornagel JH, Hilgers FJ, Keus RB, Schultze-Kool L, et al. High-dose superselective intra-arterial cisplatin and concomitant radiation (RADPLAT) for advanced head and neck cancer. Head Neck 2004;26:485–93.PubMedCrossRef
19.
go back to reference Robbins KT, Kumar P, Regine WF, Wong FS, Weir AB, III, Flick P, et al. Efficacy of targeted supradose cisplatin and concomitant radiation therapy for advanced head and neck cancer: the Memphis experience. Int J Radiat Oncol Biol Phys 1997;38:263–71.PubMed Robbins KT, Kumar P, Regine WF, Wong FS, Weir AB, III, Flick P, et al. Efficacy of targeted supradose cisplatin and concomitant radiation therapy for advanced head and neck cancer: the Memphis experience. Int J Radiat Oncol Biol Phys 1997;38:263–71.PubMed
20.
go back to reference Wolthaus JW, van Herk M, Muller SH, Belderbos JS, Lebesque JV, de Bois JA, et al. Fusion of respiration-correlated PET and CT scans: correlated lung tumour motion in anatomical and functional scans. Phys Med Biol 2005;50:1569–83.PubMedCrossRef Wolthaus JW, van Herk M, Muller SH, Belderbos JS, Lebesque JV, de Bois JA, et al. Fusion of respiration-correlated PET and CT scans: correlated lung tumour motion in anatomical and functional scans. Phys Med Biol 2005;50:1569–83.PubMedCrossRef
21.
go back to reference Belhocine T, Steinmetz N, Hustinx R, Bartsch P, Jerusalem G, Seidel L, et al. Increased uptake of the apoptosis-imaging agent (99m)Tc recombinant human Annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis. Clin Cancer Res 2002;8:2766–74.PubMed Belhocine T, Steinmetz N, Hustinx R, Bartsch P, Jerusalem G, Seidel L, et al. Increased uptake of the apoptosis-imaging agent (99m)Tc recombinant human Annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis. Clin Cancer Res 2002;8:2766–74.PubMed
22.
go back to reference Meirovitz A, Murdoch-Kinch CA, Schipper M, Pan C, Eisbruch A. Grading xerostomia by physicians or by patients after intensity-modulated radiotherapy of head-and-neck cancer. Int J Radiat Oncol Biol Phys 2006;66:445–53.PubMed Meirovitz A, Murdoch-Kinch CA, Schipper M, Pan C, Eisbruch A. Grading xerostomia by physicians or by patients after intensity-modulated radiotherapy of head-and-neck cancer. Int J Radiat Oncol Biol Phys 2006;66:445–53.PubMed
23.
go back to reference Munter MW, Karger CP, Hoffner SG, Hof H, Thilmann C, Rudat V, et al. Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy. Int J Radiat Oncol Biol Phys 2004;58:175–84.PubMedCrossRef Munter MW, Karger CP, Hoffner SG, Hof H, Thilmann C, Rudat V, et al. Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy. Int J Radiat Oncol Biol Phys 2004;58:175–84.PubMedCrossRef
24.
go back to reference Eisbruch A, Ten Haken RK, Kim HM, Marsh LH, Ship JA. Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer. Int J Radiat Oncol Biol Phys 1999;45:577–87.PubMed Eisbruch A, Ten Haken RK, Kim HM, Marsh LH, Ship JA. Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer. Int J Radiat Oncol Biol Phys 1999;45:577–87.PubMed
25.
go back to reference Valdes Olmos RA, Keus RB, Takes RP, van Tinteren H, Baris G, Hilgers FJ, et al. Scintigraphic assessment of salivary function and excretion response in radiation-induced injury of the major salivary glands. Cancer 1994;73:2886–93.PubMedCrossRef Valdes Olmos RA, Keus RB, Takes RP, van Tinteren H, Baris G, Hilgers FJ, et al. Scintigraphic assessment of salivary function and excretion response in radiation-induced injury of the major salivary glands. Cancer 1994;73:2886–93.PubMedCrossRef
26.
go back to reference Buus S, Grau C, Munk OL, Rodell A, Jensen K, Mouridsen K, et al. Individual radiation response of parotid glands investigated by dynamic (11)C-methionine PET. Radiother Oncol 2006;78:262–9.PubMedCrossRef Buus S, Grau C, Munk OL, Rodell A, Jensen K, Mouridsen K, et al. Individual radiation response of parotid glands investigated by dynamic (11)C-methionine PET. Radiother Oncol 2006;78:262–9.PubMedCrossRef
27.
go back to reference Paardekooper GM, Cammelli S, Zeilstra LJ, Coppes RP, Konings AW. Radiation-induced apoptosis in relation to acute impairment of rat salivary gland function. Int J Radiat Biol 1998;73:641–8.PubMedCrossRef Paardekooper GM, Cammelli S, Zeilstra LJ, Coppes RP, Konings AW. Radiation-induced apoptosis in relation to acute impairment of rat salivary gland function. Int J Radiat Biol 1998;73:641–8.PubMedCrossRef
28.
go back to reference Stephens LC, Schultheiss TE, Price RE, Ang KK, Peters LJ. Radiation apoptosis of serous acinar cells of salivary and lacrimal glands. Cancer 1991;67:1539–43.PubMedCrossRef Stephens LC, Schultheiss TE, Price RE, Ang KK, Peters LJ. Radiation apoptosis of serous acinar cells of salivary and lacrimal glands. Cancer 1991;67:1539–43.PubMedCrossRef
29.
go back to reference Brouckaert G, Kalai M, Krysko D, Saelens X, Vercammen D, Ndlovu M, et al. Phagocytosis of necrotic cells by macrophages is phosphatidylserine dependent and does not induce inflammatory cytokine production. Mol Biol Cell 2004;15:1089–100.PubMedCrossRef Brouckaert G, Kalai M, Krysko D, Saelens X, Vercammen D, Ndlovu M, et al. Phagocytosis of necrotic cells by macrophages is phosphatidylserine dependent and does not induce inflammatory cytokine production. Mol Biol Cell 2004;15:1089–100.PubMedCrossRef
30.
go back to reference Badoual C, Hans S, Rodriguez J, Peyrard S, Klein C, Agueznay Nel H, et al. Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res 2006;12:465–72.PubMedCrossRef Badoual C, Hans S, Rodriguez J, Peyrard S, Klein C, Agueznay Nel H, et al. Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res 2006;12:465–72.PubMedCrossRef
Metadata
Title
99mTc Hynic-rh-Annexin V scintigraphy for in vivo imaging of apoptosis in patients with head and neck cancer treated with chemoradiotherapy
Authors
Frank J. P. Hoebers
Marina Kartachova
Josien de Bois
Michiel W. M. van den Brekel
Harm van Tinteren
Marcel van Herk
Coen R. N. Rasch
Renato A. Valdés Olmos
Marcel Verheij
Publication date
01-03-2008
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 3/2008
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-007-0624-x

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