Volkan Beylergil , a , Patrick G. Morris b , Peter M. Smith-Jones a , Shanu Modi b , g , David Solit c , Clifford A. Hudis b , g , Yang Lu a , Joseph O’Donoghue d , Serge K. Lyashchenko e , Jorge A. Carrasquillo a , f , Steven M. Larson a , f , Timothy J. Akhurst a , f
06 November 2013
68Ga-1,4,7,10-Tetraazacyclododecane- N, N′, N′′, N′′′-tetraacetic acid (DOTA)-F(ab′) 2-trastuzumab [ 68Ga-DOTA-F(ab′) 2-trastuzumab] has been developed at our institution as a positron imaging reagent for assessing human epidermal growth factor receptor 2 (HER2) expression status by in-vivo imaging. Initial studies on animals demonstrated promising results in the monitoring of treatment response to heat shock protein 90-targeted drugs that inhibit the client protein HER2. We report here our initial clinical experience in the assessment of the toxicity, pharmacokinetics, biodistribution, and dosimetry profile of 68Ga-DOTA-F(ab′) 2-trastuzumab with PET/computed tomography using a mean of 236 MBq/5 mg administered intravenously.
A group of 16 women with breast cancer were enrolled in this study. The one patient who did not receive 68Ga-DOTA-F(ab′) 2-trastuzumab was excluded from analysis. Both HER2-negative ( n=7) and HER2-positive ( n=8) cases were studied. Among the latter, seven had undergone trastuzumab treatment previously and one had not.
It was determined that 68Ga-DOTA-F(ab′) 2-trastuzumab was well tolerated, with a T ½ of ∼3.6±0.9 h; the critical organ was the kidney, with a mean dose of 0.383 cGy/37 MBq; and tumor targeting was seen in 4/8 patients with HER2-positive disease.