| 1. |
- Chittenden, Sarah J., et al.
(författare)
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A Phase 1, Open-Label Study of the Biodistribution, Pharmacokinetics, and Dosimetry of Ra-223-Dichloride in Patients with Hormone-Refractory Prostate Cancer and Skeletal Metastases
- 2015
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 56:9, s. 1304-1309
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this single-site, open-label clinical trial was to determine the biodistribution, pharmacokinetics, absorbed doses, and safety from 2 sequential weight-based administrations of Ra-223-dichloride in patients with bone metastases due to castration-refractory prostate cancer. Methods: Six patients received 2 intravenous injections of Ra-223-dichloride, 6 wk apart, at 100 kBq/kg of whole-body weight. The pharmacokinetics and biodistribution as a function of time were determined, and dosimetry was performed for a range of organs including bone surfaces, red marrow, kidneys, gut, and whole body using scintigraphic imaging; external counting; and blood, fecal, and urine collection. Safety was assessed from adverse events. Results: The injected activity cleared rapidly from blood, with 1.1% remaining at 24 h. The main route of excretion was via the gut, although no significant toxicity was reported. Most of the administered activity was taken up rapidly into bone (61% at 4 h). The range of absorbed doses delivered to the bone surfaces from a emissions was 2,331-13,118 mGy/MBq. The ranges of absorbed doses delivered to the red marrow were 177-994 and 1-5 mGy/MBq from activity on the bone surfaces and from activity in the blood, respectively. No activity-limiting toxicity was observed at these levels of administration. The absorbed doses from the second treatment were correlated significantly with the first for a combination of the whole body, bone surfaces, kidneys, and liver. Conclusion: A wide range of interpatient absorbed doses was delivered to normal organs. Intrapatient absorbed doses were significantly correlated between the 2 administrations for any given patient. The lack of gastrointestinal toxicity is likely due to the low absorbed doses delivered to the gut wall from the gut contents. The lack of adverse myelotoxicity implies that the absorbed dose delivered from the circulating activity may be a more relevant guide to the potential for marrow toxicity than that due to activity on the bone surfaces.
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| 2. |
- Hindorf, Cecilia, et al.
(författare)
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Quantitative imaging of 223Ra-chloride (Alpharadin) for targeted alpha-emitting radionuclide therapy of bone metastases.
- 2012
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Ingår i: Nuclear Medicine Communications. - 1473-5628. ; 33:7, s. 726-732
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Ra is an alpha particle emitter that targets areas of increased bone turnover in bone metastases. Alpha particles account for 95% of the 27.8 MeV emitted per decay. Less than 2% of the emissions are from photons. This means that a high absorbed dose will be delivered locally, although the number of photons for imaging will be low. The purpose of this study was to investigate the possibility of quantitative imaging of Ra to enable biodistribution studies. METHODS: A Philips Forte gamma camera, equipped with a medium-energy collimator, was used. Basic imaging parameters were determined from phantom studies, and the accuracy of activity quantification was tested in a phantom study and within a patient study. RESULTS: Imaging parameters were determined for the three most suitable photon peaks from the acquired energy spectrum (82, 154 and 270 keV). Camera sensitivity is constant for circular sources with areas greater than 10 cm. The spatial resolution (full-width at half-maximum) was 1.1 cm for each of the three energy windows. The possibility for quantitative imaging was further investigated for the 82 keV energy window, which showed the highest sensitivity and spatial resolution. A phantom study showed that activity could be quantified to within 10% for a 200 ml volume placed within water containing background activity and to within 50% for a 0.5 ml phantom. Quantification of activity in bone after administrations of 100 kBq/kg of Ra-chloride proved the feasibility of quantitative imaging of patients who have received radionuclide therapy. CONCLUSION: Because of the high-energy deposition of Ra, only a low injected activity is required for therapy, which results in a low count rate for the gamma camera. Nevertheless, this study has demonstrated that it is possible to quantify uptake with a sufficient degree of accuracy to obtain clinically relevant information.
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| 3. |
- Murray, Iain, et al.
(författare)
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The potential of 223Ra and 18F-fluoride imaging to predict bone lesion response to treatment with 223Ra-dichloride in castration-resistant prostate cancer
- 2017
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; , s. 1-13
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Tidskriftsartikel (refereegranskat)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.
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