Purpose—C4, a cobalt dichloride–N-acetyl cysteine complex, is being developed as a positivesignal magnetic resonance imaging (MRI) marker to localize implanted radioactive seeds in prostate brachytherapy. We evaluated the toxicity and biodistribution of C4 in rats with the goal of simulating systemic effects of potential leakage from C4 MRI markers within the prostate.
Methods—9 μl doses (equivalent to leakage from 120 markers in a human) of control (0.9% sodium chloride), 1% (proposed for clinical use) and 10% C4 solution were injected into the prostates of male Sprague-Dawley rats via laparotomy. Organ toxicity and cobalt disposition in plasma, tissues, feces and urine were evaluated.
Results—No C4-related morbidity or mortality was observed in the biodistribution arm (60 rats). Biodistribution was measurable following 10% C4 injection: cobalt was cleared rapidly from periprostatic tissue; mean concentrations in prostate were 163 μg/g and 268 μg/g at 5 and 30 minutes but were undetectable by 60 minutes. Expected dual renal-hepatic elimination was observed with % injected dose recovered in tissues of 39.0 ±5.6% (liver) > 11.8 ±6.5% (prostate) > 5.3 ±0.9% (kidney) with low plasma concentrations detected up to 1 hr (1.40 μg/ml at 5–60 minutes). Excretion in urine was 13.1 ±4.6 % with 3.1 ±0.54 % recovered in feces by 24 hours. In the toxicity arm, three animals died in the control group and 1 each in the 1% and 10% groups from surgical or anesthesia-related complications; all others survived to scheduled termination at 14 days. No C4-related adverse clinical signs or organ toxicity was observed.
Conclusion—C4-related toxicity was not observed at exposures at least 10-fold that proposed for human use. This data demonstrating lack of systemic toxicity with dual routes of elimination in the event of in-situ rupture suggests C4 warrants further investigation as an MRI marker for prostate brachytherapy.
Frank, S. J., Johansen, M. J., Martirosyan, K. S., Gagea, M., Van Pelt, C. S., Borne, A., Carmazzi, Y., & Madden, T. (2013). A biodistribution and toxicity study of cobalt dichloride-N-acetyl cysteine in an implantable MRI marker for prostate cancer treatment. International journal of radiation oncology, biology, physics, 85(4), 1024–1030. https://doi.org/10.1016/j.ijrobp.2012.09.007
International Journal of Radiation Oncology*Biology*Physics