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

Abstract

Background/aim: The biodistribution, pharmacokinetics and therapeutic evaluation of ¹⁸⁸Re-human serum albumin microspheres (¹⁸⁸Re-HSAM) by labeling with ¹⁸⁸Re(I)-tricarbonyl ion (¹⁸⁸Re(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 ¹⁸⁸Re-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 ¹⁸⁸Re-HSAM was about 80%. After intraarterial administration of ¹⁸⁸Re-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 ¹⁸⁸Re-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 T_1/2λz of ¹⁸⁸Re-HSAM was 259.34 h after intraarterial injection. The AUC_{(0→96 h)} of ¹⁸⁸Re-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 ¹⁸⁸Re-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 ¹⁸⁸Re-HSAM were 62.5%, 32.5% and 4.4%, respectively.

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

Keywords: 188Re-HSAM; Biodistribution; GP7TB orthotopic hepatoma model; pharmacokinetics; therapeutic evaluation.