BIODISTRIBUTION AND DOSIMETRY OF IODINE-123-LABELED Z-MIVE - AN ESTROGEN-RECEPTOR RADIOLIGAND FOR BREAST-CANCER IMAGING

This study reports on the distribution and radiation dosimetry of iodi ne-123-labelled cis-11 beta-methoxy-17 alpha-iodovinyloestradiol (Z-[I -123]MIVE), a promising radioligand for imaging of oestrogen receptors (ERs) in human breast cancer. Whole-body scans were performed up to 2 4 h after intravenous injection of 138-193 MBq Z-[I-123]MIVE in five h ealthy female volunteers, four with and one without thyroid blockade, Blood samples were taken at various times up to 24 h after injection. Urine was collected up to 24 h after injection in order to calculate r enal clearance and to aid in the interpretation of whole-body clearanc e, including faecal excretion. Time-activity curves were generated for the thyroid, heart, brain, boasts and liver, by fitting the organ-spe cific geometric mean counts, obtained from regions of interest, to a m ulticompartmental model. The MIRD formulation, using 11 source organs, was applied to calculate the absorbed radiation doses for various org ans upon administration of Z-[I-123]MIVE. The images showed rapid hepa tobiliary excretion which resulted in good imaging conditions for the thoracic region. Imaging of the abdominal region was impeded due to ex tensive bowel activity. Diffuse uptake and retention of activity was s een in breast tissue, the breast-to-non-specific uptake ratio increasi ng over time. Z-[I-123]MIVE was cleared by both the kidneys and the ga strointestinal tract. At 50 h p.i. the mean excretion in urine was pre dicted to be 58%+/-14% (SD) and that in faeces 31%+/-19%. If the thyro id was not blocked, it was the most critical organ (0.33 mGy/MBq), In general, the excretory organs received the highest absorbed doses, i.e . the lower and upper large intestinal walls (0.11 and 0.098 mGy/MBq, respectively), the urinary bladder wall (0.090 mGy/MBq), the gallbladd er wall (0.087 mGy/MBq) and the small intestine (0.043 mGy/MBq). The a verage effective dose equivalent of Z-[I-123]MNE was estimated to be 0 .033 mSv/MBq. The amount of Z-[I-123]MIVE required for adequate breast cancer ER imaging results in an acceptable effective dose equivalent to the patient.