Improved overall survival and very low toxicity indicate that 223Ra-dichloride therapy may provide a new standard of care for patients with castration-resistant prostate cancer metastatic to the bone. The high linear energy transfer (LET) of α-radiation results in greater biological effectiveness than β-radiation, giving rise to cytotoxicity that is independent of dose rate, cell cycle growth phase, and oxygen concentration. Due to the α-particle high LET and short range (of a few cell diameters in tissue), microdosimetry seems almost always necessary; however, the feasibility of macrodosimetry for organs and lesions has recently been demonstrated, providing new opportunities in the clinical routine not yet explored. With the low activity of the registered use, bone lesion macrodosimetry appeared more feasible than organ dosimetry and more effective for investigating possible relationships between absorbed dose and biological/clinical effect, as response is often observed in clinical practice, whereas toxicities are mild to moderate in intensity and easily manageable with symptomatic and supportive treatments. The first injection of the treatment can be used as if it were a pretreatment tracer activity, and just three scan acquisitions are required (with a duration of about 20–30 min each), as well as other conventional imaging (such as 99mTc-diphosphonate WB scan and CT study), with a limited burden for patients and staff. A lesion/soft tissue contrast ratio on 99mTc-MDP WB scan higher than 10 would imply detectability on 223Ra spot scans. A specific preparation of the patient is not required, apart from the necessary informed consent. The correlations of the absorbed dose to lesions with the biological/clinical effects are still under consideration; however, in the perspective of the availability of new fractionation regimens, the dosimetric approach would allow a dosimetry-based choice of the administration scheduling, opening the way to dosimetry-guided radiometabolic therapy of bone metastases with α-emitters.
KeywordsBone metastases 223Ra-dichloride Radionuclide therapy Dosimetry
- 3.Pacilio M, Cassano B, Pellegrini R, Di Castro E, Zorz A, De Vincentis G, et al. Gamma camera calibrations for the Italian multicentre study for lesion dosimetry in 223Ra therapy of bone metastases. Phys Med. 2017. https://doi.org/10.1016/j.ejmp.2017.04.019.
- 5.Chittenden S, Hindorf C, Parker CC, Lewington VJ, Pratt BE, Johnson B, et al. Phase 1, open-label study of the biodistribution, pharmacokinetics and dosimetry of Radium-223 dichloride (223Ra dichloride) in patients with hormone refractory prostate cancer and skeletal metastases. J Nucl Med. 2015;56:1304–9.CrossRefPubMedGoogle Scholar
- 10.ICRP. Publication 103: the 2007 recommendations of the International Commission on Radiological Protection. Ann ICRP. 2007;2007:37.Google Scholar
- 12.CTEP. Common terminology criteria for adverse events (CTCAE) v4.0. Bethesda, MD: Cancer Therapy Evaluation Program, National Cancer Institute; 2015. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed 20 Dec 2016.
- 17.Parker CC, Pascoe S, Chodacki A, O’Sullivan JM, Germà 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.CrossRefPubMedGoogle Scholar
- 19.Cristy M, Eckerman KF. Specific absorbed fractions of energy at various ages from internal photon sources. Technical Report ORNL/TM-8381/V1. Oak Ridge, TN: Oak Ridge National Laboratory; 1987.Google Scholar
- 22.International Commission on Radiological Protection (ICRP). Age-dependent doses to members of the public from intake of radionuclides: part 2 ingestion dose coefficients. ICRP publication 67. Oxford: ICRP; 1992.Google Scholar
- 23.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 Ra-dichloride in men with castration-resistant metastatic prostate cancer. Eur J Nucl Med Mol Imaging. 2013;40:1384–93.CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Maxon HR, Schroder LE, Thomas SR, Hertzberg VS, Deutsch EA, Scher HI, Samaratunga RC, Libson KF, Williams CC, Moulton JS. Re-186(Sn) HEDP for treatment of painful osseous metastases: initial clinical experience in 20 patients with hormone-resistant prostate cancer. Radiology. 1990;176:155–9.CrossRefPubMedGoogle Scholar
- 27.Maxon HR, Schroder LE, Hertzberg VS, Thomas SR, Englaro EE, Samaratunga R, Smith H, Moulton JS, Williams CC, Ehrhardt GJ, et al. Rhenium-186(Sn)HEDP for treatment of painful osseous metastases: results of a double-blind crossover comparison with placebo. J Nucl Med. 1991;32:1877–81.PubMedGoogle Scholar