Mapping of treatment-induced apoptosis in normal structures: 99mTc-Hynic-rh-annexin V SPECT and CT image fusion

  • Marina S. Kartachova
  • Renato A. Valdés Olmos
  • Rick L. M. Haas
  • Frank J. P. Hoebers
  • Michiel W. van den Brekel
  • Nico van Zandwijk
  • Marcel van Herk
  • Marcel Verheij
Original article

Abstract

Purpose

The purpose of this study was to map treatment-induced 99mTc-Hynic-rh-annexin V uptake in normal tissues using co-registration of SPECT and CT.

Methods

Nineteen patients (11 male, 8 female, mean age 57 years) with various malignant tumours (12 lymphomas, four non-small cell lung cancers and three head and neck squamous cell carcinomas) underwent 99mTc-Hynic-rh-annexin V scintigraphy and CT before and within 48 h after the start of anticancer therapy. SPECT and CT were performed separately, with the patient in a reproducible position. Volume-based automated and manual methods were used to match functional and anatomical data. SPECT/CT co-registration was used to evaluate treatment-induced changes in the normal structures.

Results

A significant radiation field-related increase in early post-treatment 99mTc-Hynic-rh-annexin V uptake in salivary glands and bone marrow was detected in eight of nine patients. Radiation field-related increase in bone marrow activity above the baseline value was detected in all 13 irradiated patients. A minimal, symmetrical increase in activity in the salivary glands was detected after the initial course of platinum-based chemotherapy, and a diffuse prominent increase in 99mTc-Hynic-rh-annexin V in the bone marrow was detected in all cases. Precise delineation between the tumour and normal tissue tracer accumulation was accomplished in all cases using SPECT/CT co-registered volumes, enhanced by the “colourwash” technique.

Conclusion

Mapping of early treatment-related changes in annexin V uptake by SPECT/CT co-registration permits accurate evaluation of tracer distribution in normal structures and precise delineation from tumour uptake. The associations between tracer distribution in the normal tissues and treatment regimen found in this study may contribute to the evaluation of dose–effect relations in various treatment schedules.

Keywords

Apoptosis Annexin V Matching SPECT/CT 

References

  1. 1.
    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 U S A 1998;95:6349–6354CrossRefPubMedGoogle Scholar
  2. 2.
    Belhocine T, Steinmetz N, Li C, Green A, Blankenberg FG. The imaging of apoptosis with the radiolabeled annexin V: optimal timing for clinical feasibility. Technol Cancer Res Treat 2004;3:23–32PubMedGoogle Scholar
  3. 3.
    Belhocine T, Steinmetz N, Green A, Rigo P. In vivo imaging of chemotherapy-induced apoptosis in human cancers. Ann N Y Acad Sci 2003;1010:525–529CrossRefPubMedGoogle Scholar
  4. 4.
    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;8:2766–2774PubMedGoogle Scholar
  5. 5.
    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;72:333–339CrossRefPubMedGoogle Scholar
  6. 6.
    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;45:309–312PubMedGoogle Scholar
  7. 7.
    Kramer EL, Noz ME. CT-SPECT fusion for analysis of radiolabeled antibodies: applications in gastrointestinal and lung carcinoma. Int J Rad Appl Instrum B 1991;18:27–42PubMedGoogle Scholar
  8. 8.
    Loats H. CT and SPECT image registration and fusion for spatial localization of metastatic processes using radiolabeled monoclonals. J Nucl Med 1993;34:562–566PubMedGoogle Scholar
  9. 9.
    Schillaci O, Simonetti G. Fusion imaging in nuclear medicine—applications of dual-modality systems in oncology. Cancer Biother Radiopharm 2004;19:1–10CrossRefPubMedGoogle Scholar
  10. 10.
    Kemerink GJ, Liem IH, Hofstra L, Boersma HH, Buijs WC, Reutelingsperger CP, et al. Patient dosimetry of intravenously administered 99mTc-annexin V. J Nucl Med 2001;42:382–387PubMedGoogle Scholar
  11. 11.
    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;44:947–952PubMedGoogle Scholar
  12. 12.
    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;59:782–787PubMedGoogle Scholar
  13. 13.
    Vermeersch H, Loose D, Lahorte C, Mervillie K, Dierckx R, Steinmetz N, et al. 99mTc-HYNIC annexin-V imaging of primary head and neck carcinoma. Nucl Med Commun 2004;25:259–263CrossRefPubMedGoogle Scholar
  14. 14.
    DeLong MJ. Apoptosis: a modulator of cellular homeostasis and disease states. Ann N Y Acad Sci 1998;842:82–90CrossRefPubMedGoogle Scholar
  15. 15.
    Domen J, Cheshier SH, Weissman IL. The role of apoptosis in the regulation of hematopoietic stem cells: overexpression of Bcl-2 increases both their number and repopulation potential. J Exp Med 2000;191:253–264CrossRefPubMedGoogle Scholar
  16. 16.
    Ekert PG, Vaux DL. Apoptosis, haemopoiesis and leukaemogenesis. Baillieres Clin Haematol 1997;10:561–576PubMedCrossRefGoogle Scholar
  17. 17.
    Stephens LC, Schultheiss TE, Price RE, Ang KK, Peters LJ. Radiation apoptosis of serous acinar cells of salivary and lacrimal glands. Cancer 1991;67:1539–1543PubMedCrossRefGoogle Scholar
  18. 18.
    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;73:641–648CrossRefPubMedGoogle Scholar
  19. 19.
    Guchelaar HJ, Vermes A, Meerwaldt JH. Radiation-induced xerostomia: pathophysiology, clinical course and supportive treatment. Support Care Cancer 1997;5:281–288CrossRefPubMedGoogle Scholar
  20. 20.
    Zheng R, Dahlstrom KR, Wei Q, Sturgis EM. Gamma radiation-induced apoptosis, G2 delay, and the risk of salivary and thyroid carcinomas—a preliminary report. Head Neck 2004;26:612–618CrossRefPubMedGoogle Scholar
  21. 21.
    Blankenberg FG, Naumovski L, Tait JF, Post AM, Strauss HW. Imaging cyclophosphamide-induced intramedullary apoptosis in rats using 99mTc-radiolabeled annexin V. J Nucl Med 2001;42:309–316PubMedGoogle Scholar
  22. 22.
    Argiris A, Maris T, Papavasiliou G, Gouliamos A, Papavasiliou C. Radiotherapy effects on vertebral bone marrow: easily recognizable changes in T2 relaxation times. Magn Reson Imaging 1996;14:633–638CrossRefPubMedGoogle Scholar
  23. 23.
    Meyer MA, Nathan CA. Reduced F-18 fluorodeoxyglucose uptake within marrow after external beam radiation. Clin Nucl Med 2000;25:279–280CrossRefPubMedGoogle Scholar
  24. 24.
    Anton E. Ultrastructural changes of stromal cells of bone marrow and liver after cyclophosphamide treatment in mice. Tissue Cell 1997;29:1–9CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Marina S. Kartachova
    • 1
  • Renato A. Valdés Olmos
    • 1
  • Rick L. M. Haas
    • 2
  • Frank J. P. Hoebers
    • 2
  • Michiel W. van den Brekel
    • 3
  • Nico van Zandwijk
    • 4
  • Marcel van Herk
    • 2
  • Marcel Verheij
    • 2
  1. 1.Department of Nuclear MedicineThe Netherlands Cancer Institute/Antoni van Leeuwenhoek HospitalCX AmsterdamThe Netherlands
  2. 2.Department of RadiotherapyThe Netherlands Cancer Institute/Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  3. 3.Department of Head and Neck Oncology and SurgeryThe Netherlands Cancer Institute/Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  4. 4.Department of Thoracic OncologyThe Netherlands Cancer Institute/Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands

Personalised recommendations