Biliary and duodenal drainage for reducing the radiotoxic risk of antineoplastic ¹³¹I-hypericin in rat models

Abstract

Necrosis targeting radiopharmaceutical 131 I-hypericin ( 131 I-Hyp) has been studied for the therapy of solid malignancies. However, serious side effects may be caused by its unwanted radioactivity after being metabolized by the liver and excreted via bile in the digestive tract. Thus the aim of this study was to investigate two kinds of bile draining for reducing them. Thirty-eight normal rats were intravenously injected with 131 I-Hyp, 24 of which were subjected to the common bile duct (CBD) drainage for gamma counting of collected bile and tissues during 1-6, 7-12, 13-18, and 19-24 h (n ¼ 6 each group), 12 of which were divided into two groups (n ¼ 6 each group) for comparison of the drainage efficiency between CBD catheterization and duodenum intubation by collecting their bile at the first 4 h. Afterwards the 12 rats together with the last two rats which were not drained were scanned via single-photon emission computerized tomography/computed tomography (SPECT/CT) to check the differences. The images showed that almost no intestinal radioactivity can be found in those 12 drained rats while discernible radioactivity in the two undrained rats. The results also indicated that the most of the radioactivity was excreted from the bile within the first 12 h, accounting to 92% within 24 h. The radioactive metabolites in the small and large intestines peaked at 12 h and 18 h, respectively. No differences were found in those two ways of drainages. Thus bile drainage is highly recommended for the patients who were treated by 131 I-Hyp if human being and rats have a similar excretion pattern. This strategy can be clinically achieved by using a nasobiliary or nasoduodenal drainage catheter.

Preclinical Molecular PET-CT Imaging Targeting CDCP1 in Colorectal Cancer

“…ese findings may be a consequence of reduced specific binding of 89 Zr-IgG1κ resulting in increased hepatic uptake and catabolism as a mononuclear phagocyte system-containing organ [34][35][36][37][38]. Furthermore, high femoral activity was also identified in mice that received 89 Zr-IgG1κ (Figure 2(e)).…”

Imaging Cell Death: Focus on Early Evaluation of Tumor Response to Therapy

“…Although hypericin has a prominent necrosis avidity, its strong hydrophobicity and near-planar aromatic conjugated structure make it easy to form aggregates in aqueous solution, which would lead to unwanted in vivo biodistribution and slow clearance from the body after intravenous injection. − In order to seek new necrosis-avid agents with better physicochemical and pharmacokinetic properties, the necrosis avidity of anthraquinone compounds after being labeled with 131 I was evaluated in animal models of induced necrosis . Among eight anthraquinone compounds evaluated, rhein appeared to be a promising lead compound .…”