Biodistribution, Pharmacokinetics and Efficacy of 188 Re(I)-Tricarbonyl-Labeled Human Serum Albumin Microspheres in an Orthotopic Hepatoma Rat Model.

BACKGROUND/AIM: The biodistribution, pharmacokinetics and therapeutic evaluation of 188 Re-human serum albumin microspheres (188 Re-HSAM) by labeling with 188 Re(I)-tricarbonyl ion (188 Re(OH2 )3 (CO)3 )+) were investigated in a GP7TB orthotopic hepatoma rat model.

MATERIALS AND METHODS: Male F344 rats received intrahepatic inoculations with GP7TB 1 mm3 cubes. The efficacy of 188 Re-HSAM was examined following a single-dose treatment via the intraarterial route. Rats were monitored for survival until death.

RESULTS: The labeling efficiency of the 188 Re-HSAM was about 80%. After intraarterial administration of 188 Re-HSAM, radioactivity in tumors accumulated from 18.41±3.48 %ID/g at 1 h to 12.43±4.70 %ID/g at 24 h. The tumor/liver ratios ranged from 3.03 at 1 h to 1.89 at 72 h. The major uptake organs of 188 Re-HSAM were liver (73.35%ID to 48.92%ID), tumor (10.54%ID to 3.51%ID) and kidney (7.48 %ID to 0.14%ID). The T1/2λz of 188 Re-HSAM was 259.34 h after intraarterial injection. The AUC(0→96 h) of 188 Re-HSAM was 0.69 h*% ID/g. In the efficacy study, the median survival time for the rat (n=6), that received normal saline was 80 d. The median survival times for the mice treated with 10 mCi (n=4), 5.2 mCi (n=6) and 2.9 mCi (n=3) of 188 Re-HSAM were 130 d (p=0.003), 106 d (p=0.002) and 83.5 d (p=0.617), respectively. The increase in life span of 10 mCi, 5.2 mCi and 2.9 mCi of 188 Re-HSAM were 62.5%, 32.5% and 4.4%, respectively.

CONCLUSION: Administration of 188 Re-HSAM demonstrated better survival time and therapeutic efficacy at the higher dose in the GP7TB hepatoma model. These results suggested that intraarterial administration of 188 Re-HSAM could provide a benefit and promising strategy for delivery of radiotherapeutics in oncology applications.