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

Journal of Nuclear Medicine

Volumn 56, Issue 9, 2015, Pages 1304-1309

  Chittenden, Sarah J ^a   Hindorf, Cecilia ^b   Parker, Christopher C ^c   Lewington, Valerie J ^d   Pratt, Brenda E ^a   Johnson, Bernadette ^c   Flux, Glenn D ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b LUND UNIVERSITY HOSPITAL   (Sweden)

^c ROYAL MARSDEN HOSPITAL   (United Kingdom)

^d GUY S HOSPITAL   (United Kingdom)

Author keywords

223Ra; Biodistribution; Dosimetry; Molecular radiotherapy; emitter

Indexed keywords

RADIUM CHLORIDE RA 223; RADIOISOTOPE; RADIOPHARMACEUTICAL AGENT; RADIUM;

ABDOMINAL DISCOMFORT; ADULT; AGED; ALPHA RADIATION; ANEMIA; ANOREXIA; ARTICLE; BACKACHE; BLOOD ANALYSIS; BONE; BONE MARROW; BONE MARROW TOXICITY; BONE METASTASIS; BONE PAIN; CASTRATION RESISTANT PROSTATE CANCER; CLINICAL ARTICLE; CLINICAL TRIAL; CONNECTIVE TISSUE DISEASE; CONSTIPATION; DIARRHEA; DOSIMETRY; DRUG ABSORPTION; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG EXCRETION; DRUG SAFETY; DRUG TRANSPORT; FATIGUE; FECES ANALYSIS; GASTROINTESTINAL SYMPTOM; GASTROINTESTINAL TOXICITY; HEMATOLOGIC DISEASE; HUMAN; INFECTION; INFESTATION; INTESTINE; KIDNEY; LYMPHATIC SYSTEM DISEASE; MALE; METABOLIC DISORDER; MIDDLE AGED; MUSCULOSKELETAL DISEASE; NAUSEA; NUTRITIONAL DISORDER; OPEN STUDY; PERSONALIZED MEDICINE; PHASE 1 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; THORAX PAIN; URINALYSIS; URINARY TRACT INFECTION; WHOLE BODY SCINTISCANNING; ANTIBODY SPECIFICITY; BODY BURDEN; BONE NEOPLASMS; METABOLIC CLEARANCE RATE; METABOLISM; PHASE 1 CLINICAL TRIAL; PROSTATIC NEOPLASMS, CASTRATION-RESISTANT; RADIATION DOSE; SECONDARY; TISSUE DISTRIBUTION; TREATMENT OUTCOME; WHOLE BODY COUNTING;

AGED; BODY BURDEN; BONE NEOPLASMS; HUMANS; MALE; METABOLIC CLEARANCE RATE; MIDDLE AGED; ORGAN SPECIFICITY; PROSTATIC NEOPLASMS, CASTRATION-RESISTANT; RADIATION DOSAGE; RADIOISOTOPES; RADIOPHARMACEUTICALS; RADIUM; TISSUE DISTRIBUTION; TREATMENT OUTCOME; WHOLE-BODY COUNTING;

EID: 84940974848     PISSN: 01615505     EISSN: 2159662X     Source Type: Journal    
DOI: 10.2967/jnumed.115.157123     Document Type: Article

References (29)

1. Lange PH, Vasella RL. Mechanisms, hypotheses and questions regarding prostate cancer metastatic to bone. Cancer Metastasis Rev. 1998-1999;17:331-336.
2. Sartor O. Radiopharmaceutical and chemotherapy combinations in metastatic castrate-resistant prostate cancer: a new beginning. J Clin Oncol. 2009;27:2417-2418.
3. Petrylak DP, Tangen CM, Hussain MH, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351:1513-1520.
4. Tannock IF, deWit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl JMed. 2004;351:1502-1512.
5. Muralidharan A, Smith MT. Pathobiology and management of prostate cancer-induced bone pain: recent insights and future treatments. Inflammopharmacology. 2013;21:339-363.
6. Henriksen G, Fisher DR, Roeske JC, et al. Targeting of osseous sites with α-emitting 223Ra: Comparison with the β-emitter 89Sr in mice. J Nucl Med. 2003;44:252-259.
7. Ritter MA, Cleaver JE, Tobias CA. High-LET radiations induce a large proportion of non-rejoining DNA breaks. Nature. 1977;266:653-655.
8. Nilsson S, Larsen RH, Foss SD, et al. First clinical experience with α-emitting radium- 223 in the treatment of skeletal metastases. Clin Cancer Res. 2005;11:4451-4459.
9. Nilsson S, Franzen L, Parker C, et al. Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study. Lancet Oncol. 2007;8:587-594.
10. Nilsson S, Strang P, Aksnes A, et al. A randomized, dose-response, multicentre 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;48:678-686.
11. Parker CC, Pascoe S, Chodacki A, et al. A randomized, double-blind, dose-finding, multicentre, phase 2 study of radium chloride (Ra223) in patients with bone metastases and castration-resistant prostate cancer. Eur Urol. 2013;63:189-197.
12. Carrasquillo JA, O'Donoghue JA, Pandit-Taskar N. Phase I pharmacokinetic and bio-distribution study with escalating doses of 223Ra-dichloride in men with castration-resistant metastatic prostate cancer. Eur J Nucl Med Mol Imaging. 2013;40:1384-1393.
13. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213-223.
14. Sartor O, Coleman R, Nilsson S, et al. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol. 2014;15:738-746.
15. Henriksen G, Breistol K, Bruland OS, Fodstad O, Larsen RH. Significant antitumor effect from bone-seeking, alpha-particle-emitting 223Ra demonstrated in an experimental skeletal metastases model. Cancer Res. 2002;62:3120-3125.
16. Hindorf C, Chittenden S, Aksnes A-K, Parker C, Flux GD. Quantitative imaging of 223Ra-chloride (Alpharadin) for targeted alpha-emitting radionuclide therapy of bone metastases. Nucl Med Commun. 2012;33:726-732.
17. Bruland ØS, Nilsson S, Fisher DR, et al. High-linear energy transfer irradiation targeted to skeletal metastases by the a-emitter 223Ra: adjuvant or alternative to conventional modalities? Clin Cancer Res. 2006;12(20 Pt 2, suppl):6250s-6257s.
18. Lassmann M, Nosske D. Dosimetry of 223Ra-chloride: dose to normal organs and tissues. Eur J Nucl Med Mol Imaging. 2013;40:207-212.
19. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649-655.
20. International Commission on Radiological Protection (ICRP). Limits for Intakes of Radionuclides byWorkers. ICRP publication 30 (part 1). Oxford, U.K.: ICRP; 1979.
21. International Commission on Radiological Protection (ICRP). Basic Anatomical and Physiological Data for Use in Radiological Protection: The Skeleton. ICRP publication 70. Oxford, U.K.: ICRP; 1995.
22. Hindorf C, Glatting G, Ciesa C, et al. EANM Dosimetry Committee guidelines for bone marrow and whole-body dosimetry. Eur J Nucl Med Mol Imaging. 2010;37:1238-1250.
23. International Commission on Radiological Protection (ICRP). Human Alimentary Tract Model for Radiological Protection. ICRP publication 100. Oxford, U.K.: ICRP; 2006.
24. Stabin MG, Siegel JA. Physical models and dose factors for use in internal dose assessment. Health Phys. 2003;85:294-310.
25. Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med. 2005;46:1023-1027.
26. 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, U.K.: ICRP; 1992.
27. Sgouros G, Roeske JC, McDevitt MR, et al. MIRD pamphlet no. 22 (abridged): radiobiology and dosimetry of alpha-particle emitters for targeted radionuclide therapy. J Nucl Med. 2010;51:311-328.
28. Hobbs RF, Song H, Watchman CJ, et al. A bone marrow toxicity model for 223Ra a-emitter radiopharmaceutical therapy. Phys Med Biol. 2012;57:3207-3222.
29. Buckley SE, Chittenden SJ, Saran FH. Whole-body dosimetry for individualized treatment planning of 131I-MIBG radionuclide therapy for neuroblastoma. J Nucl Med. 2009;50:1518-1524.