Skip to main content
SpringerLink
Log in

Assessment of response of brain metastases to radiotherapy by PET imaging of apoptosis with 18F-ML-10

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Early assessment of tumor response to therapy is vital for treatment optimization for the individual cancer patient. Induction of apoptosis is an early and nearly universal effect of anticancer therapies. The purpose of this study was to assess the performance of 18F-ML-10, a novel PET radiotracer for apoptosis, as a tool for the early detection of response of brain metastases to whole-brain radiation therapy (WBRT).

Materials and methods

Ten patients with brain metastases treated with WBRT at 30 Gy in ten daily fractions were enrolled in this trial. Each patient underwent two 18F-ML-10 PET scans, one prior to the radiation therapy (baseline scan), and the second after nine or ten fractions of radiotherapy (follow-up scan). MRI was performed at 6–8 weeks following completion of the radiation therapy. Early treatment-induced changes in tumor 18F-ML-10 uptake on the PET scan were measured by voxel-based analysis, and were then evaluated by correlation analysis as predictors of the extent of later changes in tumor anatomical dimensions as seen on MRI scans 6–8 weeks after completion of therapy.

Results

In all ten patients, all brain lesions were detected by both MRI and the 18F-ML-10 PET scan. A highly significant correlation was found between early changes on the 18F-ML-10 scan and later changes in tumor anatomical dimensions (r = 0.9).

Conclusion

These results support the potential of 18F-ML-10 PET as a novel tool for the early detection of response of brain metastases to WBRT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Kaal EC, Niel CG, Vecht CJ. Therapeutic management of brain metastasis. Lancet Neurol. 2005;4(5):289–98.

    Article  PubMed  Google Scholar 

  2. Welzel G, Fleckenstein K, Schaefer J, Hermann B, Kraus-Tiefenbacher U, Mai SK, et al. Memory function before and after whole brain radiotherapy in patients with and without brain metastases. Int J Radiat Oncol Biol Phys. 2008;72(5):1311–8.

    Article  PubMed  Google Scholar 

  3. Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004;363(9422):1665–72.

    Article  PubMed  Google Scholar 

  4. Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006;295(21):2483–91.

    Article  PubMed  CAS  Google Scholar 

  5. Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990;322(8):494–500.

    Article  PubMed  CAS  Google Scholar 

  6. Mehta MP, Paleologos NA, Mikkelsen T, Robinson PD, Ammirati M, Andrews DW, et al. The role of chemotherapy in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2010;96(1):71–83.

    Article  PubMed  Google Scholar 

  7. Mehta MP, Tsao MN, Whelan TJ, Morris DE, Hayman JA, Flickinger JC, et al. The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys. 2005;63(1):37–46.

    Article  PubMed  Google Scholar 

  8. Li J, Bentzen SM, Renschler M, Mehta MP. Regression after whole-brain radiation therapy for brain metastases correlates with survival and improved neurocognitive function. J Clin Oncol. 2007;25(10):1260–6.

    Article  PubMed  Google Scholar 

  9. Maddika S, Ande SR, Panigrahi S, Paranjothy T, Weglarczyk K, Zuse A, et al. Cell survival, cell death and cell cycle pathways are interconnected: implications for cancer therapy. Drug Resist Updat. 2007;10(1-2):13–29.

    Article  PubMed  CAS  Google Scholar 

  10. Call JA, Eckhardt SG, Camidge DR. Targeted manipulation of apoptosis in cancer treatment. Lancet Oncol. 2008;9(10):1002–11.

    Article  PubMed  CAS  Google Scholar 

  11. Meiler J, Schuler M. Therapeutic targeting of apoptotic pathways in cancer. Curr Drug Targets. 2006;7(10):1361–9.

    Article  PubMed  CAS  Google Scholar 

  12. Hu W, Kavanagh JJ. Anticancer therapy targeting the apoptotic pathway. Lancet Oncol. 2003;4(12):721–9.

    Article  PubMed  CAS  Google Scholar 

  13. Fernandez-Luna JL. Apoptosis regulators as targets for cancer therapy. Clin Transl Oncol. 2007;9(9):555–62.

    Article  PubMed  CAS  Google Scholar 

  14. Meyn RE, Milas L, Ang KK. The role of apoptosis in radiation oncology. Int J Radiat Biol. 2009;85(2):107–15.

    Article  PubMed  CAS  Google Scholar 

  15. Cohen A, Shirvan A, Levin G, Grimberg H, Reshef A, Ziv I. From the Gla domain to a novel small-molecule detector of apoptosis. Cell Res. 2009;19(5):625–37.

    Article  PubMed  CAS  Google Scholar 

  16. Hoglund J, Shirvan A, Antoni G, Gustavsson SA, Langstrom B, Ringheim A, et al. 18F-ML-10, a PET tracer for apoptosis: first human study. J Nucl Med. 2011;52(5):720–5.

    Article  PubMed  Google Scholar 

  17. Reshef A, Shirvan A, Waterhouse RN, Grimberg H, Levin G, Cohen A, et al. Molecular imaging of neurovascular cell death in experimental cerebral stroke by PET. J Nucl Med. 2008;49(9):1520–8.

    Article  PubMed  CAS  Google Scholar 

  18. Reshef A, Shirvan A, Akselrod-Ballin A, Wall A, Ziv I. Small-molecule biomarkers for clinical PET imaging of apoptosis. J Nucl Med. 2010;51(6):837–40.

    Article  PubMed  CAS  Google Scholar 

  19. Galban CJ, Chenevert TL, Meyer CR, Tsien C, Lawrence TS, Hamstra DA, et al. Prospective analysis of parametric response map-derived MRI biomarkers: identification of early and distinct glioma response patterns not predicted by standard radiographic assessment. Clin Cancer Res. 2011;17(14):4751–60.

    Article  PubMed  Google Scholar 

  20. Kwee TC, Galban CJ, Tsien C, Junck L, Sundgren PC, Ivancevic MK, et al. Comparison of apparent diffusion coefficients and distributed diffusion coefficients in high-grade gliomas. J Magn Reson Imaging. 2010;31(3):531–7.

    Article  PubMed  Google Scholar 

  21. Ma B, Meyer CR, Pickles MD, Chenevert TL, Bland PH, Galban CJ, et al. Voxel-by-voxel functional diffusion mapping for early evaluation of breast cancer treatment. Inf Process Med Imaging. 2009;21:276–87.

    Article  PubMed  Google Scholar 

  22. Moffat BA, Chenevert TL, Lawrence TS, Meyer CR, Johnson TD, Dong Q, et al. Functional diffusion map: a noninvasive MRI biomarker for early stratification of clinical brain tumor response. Proc Natl Acad Sci U S A. 2005;102(15):5524–9.

    Google Scholar 

  23. Aloya R, Shirvan A, Grimberg H, Reshef A, Levin G, Kidron D, et al. Molecular imaging of cell death in vivo by a novel small molecule probe. Apoptosis. 2006;11(12):2089–101.

    Article  PubMed  Google Scholar 

  24. Hoebers FJ, Kartachova M, de Bois J, van den Brekel MW, van Tinteren H, van Herk M, et al. 99mTc Hynic-rh-Annexin V scintigraphy for in vivo imaging of apoptosis in patients with head and neck cancer treated with chemoradiotherapy. Eur J Nucl Med Mol Imaging. 2008;35(3):509–18.

    Article  PubMed  CAS  Google Scholar 

  25. Yagle KJ, Eary JF, Tait JF, Grierson JR, Link JM, Lewellen B, et al. Evaluation of 18F-annexin V as a PET imaging agent in an animal model of apoptosis. J Nucl Med. 2005;46(4):658–66.

    PubMed  CAS  Google Scholar 

  26. Nguyen QD, Smith G, Glaser M, Perumal M, Arstad E, Aboagye EO. Positron emission tomography imaging of drug-induced tumor apoptosis with a caspase-3/7 specific [18F]-labeled isatin sulfonamide. Proc Natl Acad Sci U S A. 2009;106(38):16375–80.

    Article  PubMed  CAS  Google Scholar 

  27. Zhou D, Chu W, Chen DL, Wang Q, Reichert DE, Rothfuss J, et al. [18F]- and [11C]-labeled N-benzyl-isatin sulfonamide analogues as PET tracers for apoptosis: synthesis, radiolabeling mechanism, and in vivo imaging study of apoptosis in Fas-treated mice using [11C]WC-98. Org Biomol Chem. 2009;7(7):1337–48.

    Article  PubMed  CAS  Google Scholar 

  28. Ariji Y, Fuwa N, Kodaira T, Tachibana H, Nakamura T, Satoh Y, et al. False-positive positron emission tomography appearance with 18F-fluorodeoxyglucose after definitive radiotherapy for cancer of the mobile tongue. Br J Radiol. 2009;82(973):e3–7.

    Article  PubMed  CAS  Google Scholar 

  29. Hentschel M, Appold S, Schreiber A, Abolmaali N, Abramyuk A, Dorr W, et al. Early FDG PET at 10 or 20 Gy under chemoradiotherapy is prognostic for locoregional control and overall survival in patients with head and neck cancer. Eur J Nucl Med Mol Imaging. 2011;38(7):1203–11.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

This trial was financially supported by Aposense Ltd.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Nuclear Medicine, Radiology and Neurology, Rabin Medical Center, Petach-Tikvah, Israel

    Aaron M. Allen, Adam Steinmetz, Yulia Kundel, Edna Inbar, Ruth Djaldetti, Eyal Fenig & Ilan Ziv

  2. Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel

    Aaron M. Allen, Adam Steinmetz, Yulia Kundel, Edna Inbar, Ruth Djaldetti, Eyal Fenig & Ilan Ziv

  3. Aposense Ltd., Petach-Tikvah, Israel

    Miri Ben-Ami, Ayelet Reshef, Tal Davidson & Ilan Ziv

  4. Department of Oncology, Radiotherapy Unit Davvidoff Center, Rabin Medical Center, Petach-Tikvah, Israel

    Aaron M. Allen

Authors
  1. Aaron M. Allen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Miri Ben-Ami
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ayelet Reshef
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adam Steinmetz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yulia Kundel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Edna Inbar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ruth Djaldetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tal Davidson
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eyal Fenig
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ilan Ziv
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aaron M. Allen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Allen, A.M., Ben-Ami, M., Reshef, A. et al. Assessment of response of brain metastases to radiotherapy by PET imaging of apoptosis with 18F-ML-10. Eur J Nucl Med Mol Imaging 39, 1400–1408 (2012). https://doi.org/10.1007/s00259-012-2150-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-012-2150-8

Keywords

Search

Navigation