Pharmacokinetics of single dose radium-223 dichloride (BAY 88-8223) in Japanese patients with castration-resistant prostate cancer and bone metastases.
OBJECTIVE
This open-label, non-randomized, phase I study examined the pharmacokinetics (PK) and radiation dosimetry of a single dose of radium-223 in Japanese patients with castration-resistant prostate cancer (CRPC) and bone metastases.


METHODS
Six male Japanese patients (mean age 72.5 years, range 65-79 years) with histologically or cytologically confirmed stage IV adenocarcinoma of the prostate were recruited. A single IV dose of radium-223 was delivered intravenously (IV) via slow bolus over a 2-5 min period: Cohort 1 received 50 kBq/kg and Cohort 2 received 100 kBq/kg.


RESULTS
Following IV injection, radium-223 was rapidly eliminated from the blood in a multi-phasic manner. The fraction of the injected activity of radium-223 retained in the whole body 24 h following injection was 85 %. Biodistribution results showed initial bone uptake was 52 % (range 41-57 %). The maximum activity of radium-223 in the bone was observed within 2 h of dosing. Activity of radium-223 passed through the small intestine within 24 h. No activity was detected in other organs. The major radiation dose from radium-223 was found in osteogenic cells; calculated absorbed doses in osteogenic cells and in the red marrow were 0.76 Gy/MBq and 0.09 Gy/MBq, respectively.


CONCLUSIONS
In Japanese patients with CRPC and bone metastases, radium-223 (IV) achieved maximum activity in the bone rapidly and passed through the intestine within 24 h, without signs of activity in other organs. The PK profile and absorbed radiation dose in organs and tissues in Japanese patients were similar to data from non-Japanese patients. Trial registration identification: NCT01565746.
Department of Radiology, Yokohama City University, 3-9 Fukuura, Yokohama, 236-0004, Japan. kei-yoshida@nyc.odn.ne.jp.
Keisuke
K
Yoshida
Department of Radiation Oncology/Diagnostic Radiology, Tohoku University Hospital, Sendai, Japan.
Tomohiro
T
Kaneta
Radiation Oncology, Shonan Kamakura General Hospital, Kamakura, Japan.
Shoko
S
Takano
Department of Radiology, Yokohama City University, 3-9 Fukuura, Yokohama, 236-0004, Japan.
Madoka
M
Sugiura
Department of Radiology, Yokohama City University, 3-9 Fukuura, Yokohama, 236-0004, Japan.
Tsuyoshi
T
Kawano
Department of Radiology, Yokohama City University, 3-9 Fukuura, Yokohama, 236-0004, Japan.
Ayako
A
Hino
Department of Diagnostic Radiology, Yokohama City University Medical Center, Yokohama, Japan.
Tou
T
Yamamoto
Saitama Central Clinic, Saitama, Japan.
Kazuya
K
Shizukuishi
Clinical Sciences Japan, Bayer Yakuhin Ltd., Osaka, Japan.
Masato
M
Kaneko
Clinical Sciences, Bayer Pharma AG, Berlin, Germany.
Christian
C
Zurth
Department of Radiology, Yokohama City University, 3-9 Fukuura, Yokohama, 236-0004, Japan.
Tomio
T
Inoue
D000368:Aged; D001859:Bone Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D006801:Humans; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000473:pathology*; D011829:Radiation Dosage; D011868:Radioisotopes / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D011874:Radiometry; D011879:Radiotherapy Dosage; D011883:Radium / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D014018:Tissue Distribution
D011868:Radioisotopes; C581106:radium Ra 223 dichloride; D011883:Radium
Castration-resistant prostate cancer; Metastases; Pharmacokinetics; Radium-223