This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Henriksen, G. Articles by Larsen, R. H. Search for Related Content PubMed PubMed Citation Articles by Henriksen, G. Articles by Larsen, R. H.

Significant Antitumor Effect from Bone-seeking, -Particle-emitting ²²³Ra Demonstrated in an Experimental Skeletal Metastases Model¹

Department of Chemistry, University of Oslo, Oslo, Norway [G. H., R. H. L.]; Anticancer Therapeutic Inventions AS, N-0884 Oslo [G. H., R. H. L.]; Department of Tumor Biology, [K. B., Ø. F.]; and Department of Oncology, The Norwegian Radium Hospital, N-0310 Oslo, [Ø. S. B.] Norway

The therapeutic efficacy of the -particle-emitting radionuclide ²²³Ra (t_1/2 = 11.4 days) in the treatment against experimental skeletal metastases in rats was addressed. Biodistribution studies, involving measurement of ²²³Ra in bone marrow samples, were performed in rats after i.v. injection. To study the therapeutic effect of ²²³Ra, an experimental skeletal metastases model in nude rats was used. Animals that had received 10⁶ MT-1 human breast cancer cells were treated with ²²³Ra doses in the range of 6–30 kBq after 7 days. The biodistribution experiment demonstrated that ²²³Ra was selectively concentrated in bone as compared with soft tissues. The femur content of ²²³Ra was 800 ± 56% of injected dose per gram tissue times gram body weight (b.w.; mean ± SD) 1 day after the injection and 413 ± 23% of injected dose per gram tissue times gram b.w. at 14 days. The femur:kidney ratio increased from (5.9 ± 2.0)·10² at 1 day to (7.2 ± 3.0)·10² at 14 days, whereas the femur:liver ratio increased from (6.2 ± 0.2)·10² to (9.1 ± 6.6)·10². Femur:spleen ratio increased from (8.1 ± 0.3)·10² at 1 day to (6.4 2.2)·10³ at 14 days. The femoral bone:marrow ratio was 6.5 ± 2.1 after day 1 and larger than 15 at day 14. All of the tumor-bearing control animals had to be sacrificed because of tumor-induced paralysis 20–30 days after injection with tumor cells, whereas the rats treated with 10 kBq of ²²³Ra had a significantly increased symptom-free survival (P < 0.05). Also 36% (5 of 14) of rats treated with 11 kBq and 40% (2 of 5) of rats treated with 10 kBq were alive beyond the 67-day follow-up period. No signs of bone marrow toxicity or b.w. loss were observed in the groups of treated animals. The significant antitumor effect of ²²³Ra at doses that are tolerated by the bone marrow is most likely linked to the intense and highly localized radiation dose from -particles at the bone surfaces. The results of this study indicate that ²²³Ra should be additionally studied as a potential bone marrow-sparing treatment of cancers involving the skeleton.

This article has been cited by other articles:

				K. Ogawa, T. Mukai, D. Asano, H. Kawashima, S. Kinuya, K. Shiba, K. Hashimoto, H. Mori, and H. Saji Therapeutic Effects of a 186Re-Complex-Conjugated Bisphosphonate for the Palliation of Metastatic Bone Pain in an Animal Model J. Nucl. Med., January 1, 2007; 48(1): 122 - 127. [Abstract] [Full Text] [PDF]

				O. S. Bruland, S. Nilsson, D. R. Fisher, and R. H. Larsen High-Linear Energy Transfer Irradiation Targeted to Skeletal Metastases by the {alpha}-Emitter 223Ra: Adjuvant or Alternative to Conventional Modalities? Clin. Cancer Res., October 15, 2006; 12(20): 6250s - 6257s. [Abstract] [Full Text] [PDF]

				P. M. Anderson, G. A. Wiseman, L. Erlandson, V. Rodriguez, B. Trotz, S. A. Dubansky, and K. Albritton Gemcitabine Radiosensitization after High-Dose Samarium for Osteoblastic Osteosarcoma Clin. Cancer Res., October 1, 2005; 11(19): 6895 - 6900. [Abstract] [Full Text] [PDF]

				C. J. Watchman, D. W. Jokisch, P. W. Patton, D. A. Rajon, G. Sgouros, and W. E. Bolch Absorbed Fractions for {alpha}-Particles in Tissues of Trabecular Bone: Considerations of Marrow Cellularity Within the ICRP Reference Male J. Nucl. Med., July 1, 2005; 46(7): 1171 - 1185. [Abstract] [Full Text] [PDF]

				S. Nilsson, R. H. Larsen, S. D. Fossa, L. Balteskard, K. W. Borch, J.-E. Westlin, G. Salberg, and O. S. Bruland First Clinical Experience with {alpha}-Emitting Radium-223 in the Treatment of Skeletal Metastases Clin. Cancer Res., June 15, 2005; 11(12): 4451 - 4459. [Abstract] [Full Text] [PDF]

				G. Henriksen, D. R. Fisher, J. C. Roeske, O. S. Bruland, and R. H. Larsen Targeting of Osseous Sites with {alpha}-Emitting 223Ra: Comparison with the {beta}-Emitter 89Sr in Mice J. Nucl. Med., February 1, 2003; 44(2): 252 - 259. [Abstract] [Full Text] [PDF]