Top

European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-08-2006 | Original article

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

Authors: 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

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 8/2006

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.

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;95:6349–6354CrossRefPubMed

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;3:23–32PubMed

Belhocine T, Steinmetz N, Green A, Rigo P. In vivo imaging of chemotherapy-induced apoptosis in human cancers. Ann N Y Acad Sci 2003;1010:525–529CrossRefPubMed

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;8:2766–2774PubMed

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;72:333–339CrossRefPubMed

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;45:309–312PubMed

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;18:27–42PubMed

Loats H. CT and SPECT image registration and fusion for spatial localization of metastatic processes using radiolabeled monoclonals. J Nucl Med 1993;34:562–566PubMed

Schillaci O, Simonetti G. Fusion imaging in nuclear medicine—applications of dual-modality systems in oncology. Cancer Biother Radiopharm 2004;19:1–10CrossRefPubMed

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;42:382–387PubMed

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;44:947–952PubMed

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;59:782–787PubMed

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;25:259–263CrossRefPubMed

14.

DeLong MJ. Apoptosis: a modulator of cellular homeostasis and disease states. Ann N Y Acad Sci 1998;842:82–90CrossRefPubMed

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;191:253–264CrossRefPubMed

16.

Ekert PG, Vaux DL. Apoptosis, haemopoiesis and leukaemogenesis. Baillieres Clin Haematol 1997;10:561–576PubMedCrossRef

17.

Stephens LC, Schultheiss TE, Price RE, Ang KK, Peters LJ. Radiation apoptosis of serous acinar cells of salivary and lacrimal glands. Cancer 1991;67:1539–1543PubMedCrossRef

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;73:641–648CrossRefPubMed

19.

Guchelaar HJ, Vermes A, Meerwaldt JH. Radiation-induced xerostomia: pathophysiology, clinical course and supportive treatment. Support Care Cancer 1997;5:281–288CrossRefPubMed

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;26:612–618CrossRefPubMed

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;42:309–316PubMed

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;14:633–638CrossRefPubMed

23.

Meyer MA, Nathan CA. Reduced F-18 fluorodeoxyglucose uptake within marrow after external beam radiation. Clin Nucl Med 2000;25:279–280CrossRefPubMed

24.

Anton E. Ultrastructural changes of stromal cells of bone marrow and liver after cyclophosphamide treatment in mice. Tissue Cell 1997;29:1–9CrossRefPubMed

Title: Mapping of treatment-induced apoptosis in normal structures: 99mTc-Hynic-rh-annexin V SPECT and CT image fusion
Authors: 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
Publication date: 01-08-2006
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 8/2006
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-006-0070-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 8/2006

Imaging of adrenocortical metastases with [11C]metomidate

Is PET/CT necessary in paediatric oncology?

Simplified quantification of small animal [18F]FDG PET studies using a standard arterial input function

Impact of sympathetic innervation on recurrent life-threatening arrhythmias in the follow-up of patients with idiopathic ventricular fibrillation

The future of cardiovascular imaging and non-invasive diagnosis

Differentiation of tumour and inflammation: characterisation of [methyl-3H]methionine (MET) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) uptake in human tumour and inflammatory cells