Skip to main content
Top
Published in: European Journal of Nuclear Medicine and Molecular Imaging 11/2017

Open Access 01-10-2017 | Original Article

The potential of 223Ra and 18F-fluoride imaging to predict bone lesion response to treatment with 223Ra-dichloride in castration-resistant prostate cancer

Authors: Iain Murray, Sarah J. Chittenden, Ana M. Denis-Bacelar, Cecilia Hindorf, Christopher C. Parker, Sue Chua, Glenn D. Flux

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 11/2017

Login to get access

Abstract

Purpose

The aims of this study were to calculate bone lesion absorbed doses resulting from a weight-based administration of 223Ra-dichloride, to assess the relationship between those doses and corresponding 18F-fluoride uptake and to assess the potential of quantitative 18F-fluoride imaging to predict response to treatment.

Methods

Five patients received two intravenous injections of 223Ra-dichloride, 6 weeks apart, at 110 kBq/kg whole-body weight. The biodistribution of 223Ra in metastatic lesions as a function of time after administration as well as associated lesion dosimetry were determined from serial 223Ra scans. PET/CT imaging using 18F-fluoride was performed prior to the first treatment (baseline), and at week 6 immediately before the second treatment and at week 12 after baseline.

Results

Absorbed doses to metastatic bone lesions ranged from 0.6 Gy to 44.1 Gy. For individual patients, there was an average factor difference of 5.3 (range 2.5–11.0) between the maximum and minimum lesion dose. A relationship between lesion-absorbed doses and serial changes in 18F-fluoride uptake was demonstrated (r2 = 0.52). A log-linear relationship was demonstrated (r2 = 0.77) between baseline measurements of 18F-fluoride uptake prior to 223Ra-dichloride therapy and changes in uptake 12 weeks after the first cycle of therapy. Correlations were also observed between both 223Ra and 18F-fluoride uptake in lesions (r = 0.75) as well as between 223Ra absorbed dose and 18F-fluoride uptake (r = 0.96).

Conclusions

There is both inter-patient and intra-patient heterogeneity of absorbed dose estimates to metastatic lesions. A relationship between 223Ra lesion absorbed dose and subsequent lesion response was observed. Analysis of this small group of patients suggests that baseline uptake of 18F-fluoride in bone metastases is significantly correlated with corresponding uptake of 223Ra, the associated 223Ra absorbed dose and subsequent lesion response to treatment.
Literature
6.
go back to reference Hindorf C, Chittenden S, Aksnes AK, Parker C, Flux GD. Quantitative imaging of Ra-223-chloride (Alpharadin) for targeted alpha-emitting radionuclide therapy of bone metastases. Nucl med Commun. 2012;33:726–32.CrossRefPubMed Hindorf C, Chittenden S, Aksnes AK, Parker C, Flux GD. Quantitative imaging of Ra-223-chloride (Alpharadin) for targeted alpha-emitting radionuclide therapy of bone metastases. Nucl med Commun. 2012;33:726–32.CrossRefPubMed
8.
go back to reference Chittenden SJ, Hindorf C, Parker CC, Lewington VJ, Pratt BE, Johnson B, et al. A phase 1, open-label study of the Biodistribution, pharmacokinetics, and Dosimetry of 223Ra-dichloride in patients with hormone-refractory prostate cancer and skeletal metastases. J Nucl med. 2015;56:1304–9. doi:10.2967/jnumed.115.157123.CrossRefPubMed Chittenden SJ, Hindorf C, Parker CC, Lewington VJ, Pratt BE, Johnson B, et al. A phase 1, open-label study of the Biodistribution, pharmacokinetics, and Dosimetry of 223Ra-dichloride in patients with hormone-refractory prostate cancer and skeletal metastases. J Nucl med. 2015;56:1304–9. doi:10.​2967/​jnumed.​115.​157123.CrossRefPubMed
9.
10.
go back to reference Carrasquillo JA, O'Donoghue JA, Pandit-Taskar N, Humm JL, Rathkopf DE, Slovin SF, et al. Phase I pharmacokinetic and biodistribution study with escalating doses of (2)(2)(3)Ra-dichloride in men with castration-resistant metastatic prostate cancer. Eur J Nucl med Mol Imaging. 2013;40:1384–93. doi:10.1007/s00259-013-2427-6.CrossRefPubMedPubMedCentral Carrasquillo JA, O'Donoghue JA, Pandit-Taskar N, Humm JL, Rathkopf DE, Slovin SF, et al. Phase I pharmacokinetic and biodistribution study with escalating doses of (2)(2)(3)Ra-dichloride in men with castration-resistant metastatic prostate cancer. Eur J Nucl med Mol Imaging. 2013;40:1384–93. doi:10.​1007/​s00259-013-2427-6.CrossRefPubMedPubMedCentral
11.
go back to reference Pacilio M, Ventroni G, De Vincentis G, Cassano B, Pellegrini R, Di Castro E, et al. Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting Ra-dichloride. Eur J Nucl med Mol Imaging. 2015; doi:10.1007/s00259-015-3150-2. Pacilio M, Ventroni G, De Vincentis G, Cassano B, Pellegrini R, Di Castro E, et al. Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting Ra-dichloride. Eur J Nucl med Mol Imaging. 2015; doi:10.​1007/​s00259-015-3150-2.
12.
go back to reference Nilsson S, Strang P, Aksnes AK, Franzen L, Olivier P, Pecking A, et al. A randomized, dose-response, multicenter phase II study of radium-223 chloride for the palliation of painful bone metastases in patients with castration-resistant prostate cancer. Eur J Cancer. 2012;48:678–86. doi:10.1016/j.ejca.2011.12.023.CrossRefPubMed Nilsson S, Strang P, Aksnes AK, Franzen L, Olivier P, Pecking A, et al. A randomized, dose-response, multicenter phase II study of radium-223 chloride for the palliation of painful bone metastases in patients with castration-resistant prostate cancer. Eur J Cancer. 2012;48:678–86. doi:10.​1016/​j.​ejca.​2011.​12.​023.CrossRefPubMed
13.
go back to reference Parker CC, Pascoe S, Chodacki A, O'Sullivan JM, Germa JR, O'Bryan-Tear CG, et al. A randomized, double-blind, dose-finding, multicenter, phase 2 study of radium chloride (Ra 223) in patients with bone metastases and castration-resistant prostate cancer. Eur Urol. 2013;63:189–97. doi:10.1016/j.eururo.2012.09.008.CrossRefPubMed Parker CC, Pascoe S, Chodacki A, O'Sullivan JM, Germa JR, O'Bryan-Tear CG, et al. A randomized, double-blind, dose-finding, multicenter, phase 2 study of radium chloride (Ra 223) in patients with bone metastases and castration-resistant prostate cancer. Eur Urol. 2013;63:189–97. doi:10.​1016/​j.​eururo.​2012.​09.​008.CrossRefPubMed
16.
go back to reference Piert M, Zittel TT, Becker GA, Jahn M, Stahlschmidt A, Maier G, et al. Assessment of porcine bone metabolism by dynamic [F-18]fluoride ion PET: correlation with bone histomorphometry. J Nucl med. 2001;42:1091–100.PubMed Piert M, Zittel TT, Becker GA, Jahn M, Stahlschmidt A, Maier G, et al. Assessment of porcine bone metabolism by dynamic [F-18]fluoride ion PET: correlation with bone histomorphometry. J Nucl med. 2001;42:1091–100.PubMed
18.
go back to reference Keightley J, Pearce A, Fenwick A, Collins S, Ferreira K, Johansson L. Standardisation of 223Ra by liquid scintillation counting techniques and comparison with secondary measurements. Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for use in Agriculture, Industry and Medicine. 2014;95C:114–21. doi:10.1016/j.apradiso.2014.10.009. Keightley J, Pearce A, Fenwick A, Collins S, Ferreira K, Johansson L. Standardisation of 223Ra by liquid scintillation counting techniques and comparison with secondary measurements. Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for use in Agriculture, Industry and Medicine. 2014;95C:114–21. doi:10.​1016/​j.​apradiso.​2014.​10.​009.
19.
20.
go back to reference Cook GJR, Parker C, Chua S, Johnson B, Aksnes AK, Lewington VJ. F-18-fluoride PET: changes in uptake as a method to assess response in bone metastases from castrate-resistant prostate cancer patients treated with Ra-223-chloride (Alpharadin). EJNMMI Res. 2011;1. Cook GJR, Parker C, Chua S, Johnson B, Aksnes AK, Lewington VJ. F-18-fluoride PET: changes in uptake as a method to assess response in bone metastases from castrate-resistant prostate cancer patients treated with Ra-223-chloride (Alpharadin). EJNMMI Res. 2011;1.
21.
go back to reference Buijs WCAM, Siegel JA, Boerman OC, Corstens FHM. Absolute organ activity estimated by five different methods of background correction. J Nucl med. 1998;39:2167–72.PubMed Buijs WCAM, Siegel JA, Boerman OC, Corstens FHM. Absolute organ activity estimated by five different methods of background correction. J Nucl med. 1998;39:2167–72.PubMed
22.
go back to reference Siegel JA, Thomas SR, Stubbs JB, Stabin MG, Hays MT, Koral KF, et al. MIRD pamphlet no. 16: techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. J Nucl med. 1999;40:37s–61s.PubMed Siegel JA, Thomas SR, Stubbs JB, Stabin MG, Hays MT, Koral KF, et al. MIRD pamphlet no. 16: techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. J Nucl med. 1999;40:37s–61s.PubMed
23.
go back to reference Hatt M, Cheze le Rest C, Turzo A, Roux C, Visvikis D. A fuzzy locally adaptive Bayesian segmentation approach for volume determination in PET. IEEE Trans med Imaging. 2009;28:881–93.CrossRefPubMedPubMedCentral Hatt M, Cheze le Rest C, Turzo A, Roux C, Visvikis D. A fuzzy locally adaptive Bayesian segmentation approach for volume determination in PET. IEEE Trans med Imaging. 2009;28:881–93.CrossRefPubMedPubMedCentral
26.
go back to reference Hindorf C. Dosimetry for radionuclide therapy with 223Ra-Cl2 with the biokinetics for the daughters measured separately. In preparation. Hindorf C. Dosimetry for radionuclide therapy with 223Ra-Cl2 with the biokinetics for the daughters measured separately. In preparation.
28.
go back to reference BIPM, IEC, IFCC, ILAC, ISO, IUPAC, et al. Evaluation of measurement data - Guide to the expression of uncertainty in measurement. Jt Comm Guides Metrol (JCMG). 2008;101. BIPM, IEC, IFCC, ILAC, ISO, IUPAC, et al. Evaluation of measurement data - Guide to the expression of uncertainty in measurement. Jt Comm Guides Metrol (JCMG). 2008;101.
29.
31.
go back to reference Sgouros G, Roeske JC, McDevitt MR, Palm S, Allen BJ, Fisher DR, et al. MIRD pamphlet no. 22 (abridged): radiobiology and dosimetry of alpha-particle emitters for targeted radionuclide therapy. J Nucl med. 2010;51:311–28. doi:10.2967/jnumed.108.058651.CrossRefPubMed Sgouros G, Roeske JC, McDevitt MR, Palm S, Allen BJ, Fisher DR, et al. MIRD pamphlet no. 22 (abridged): radiobiology and dosimetry of alpha-particle emitters for targeted radionuclide therapy. J Nucl med. 2010;51:311–28. doi:10.​2967/​jnumed.​108.​058651.CrossRefPubMed
32.
go back to reference Feinendegen LE, McClure JJ. Meeting report - alpha-emitters for medical therapy - workshop of the United States Department of Energy - Denver, Colorado, may 30-31, 1996. Radiat res. 1997;148:195–201. doi:10.2307/3579579.CrossRef Feinendegen LE, McClure JJ. Meeting report - alpha-emitters for medical therapy - workshop of the United States Department of Energy - Denver, Colorado, may 30-31, 1996. Radiat res. 1997;148:195–201. doi:10.​2307/​3579579.CrossRef
Metadata
Title
The potential of 223Ra and 18F-fluoride imaging to predict bone lesion response to treatment with 223Ra-dichloride in castration-resistant prostate cancer
Authors
Iain Murray
Sarah J. Chittenden
Ana M. Denis-Bacelar
Cecilia Hindorf
Christopher C. Parker
Sue Chua
Glenn D. Flux
Publication date
01-10-2017
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 11/2017
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-017-3744-y

Other articles of this Issue 11/2017

European Journal of Nuclear Medicine and Molecular Imaging 11/2017 Go to the issue