In vivo tumour imaging employing regional delivery of novel gallium radiolabelled polymer composites.

Background: Understanding the regional vascular delivery of particles to tumour sites is a prerequisite for developing new diagnostic and therapeutic composites for treatment of oncology patients. We describe a novel imageable Ga-radiolabelled polymer composite that is biocompatible in an animal tumour model and can be used for preclinical imaging investigations of the transit of different sized particles through arterial networks of normal and tumour-bearing organs.

Results: Radiolabelling of polymer microspheres with Ga was achieved using a simple mix and wash method, with tannic acid as an immobilising agent.

Tc-radiolabeled composites enabling in vivo imaging of arterial dispersal and retention of microspheres in the vascular network of rabbit lungs, liver, and liver tumors.

Purpose: Selective internal radiation therapy (SIRT) is an effective treatment option for liver tumors, using Y-90-loaded polymer microspheres that are delivered via catheterization of the hepatic artery. Since Y-90 is a beta emitter and not conveniently imaged by standard clinical instrumentation, dosimetry is currently evaluated in each patient using a surrogate particle, Technetium-labeled macroaggregated albumin (Tc-MAA). We report a new composite consisting of Tc-labeled nanoparticles attached to the same polymer microspheres as used for SIRT, which can be imaged with standard SPECT.

Phase II trial of selective internal radiation therapy and systemic chemotherapy for liver-predominant metastases from pancreatic adenocarcinoma.

Background: This prospective, open-label phase II study assessed the impact of liver-directed therapy with selective internal radiation therapy (SIRT) and systemic chemotherapy on progression-free survival (PFS) in liver-dominant metastatic pancreatic adenocarcinoma.

Methods: Patients received yttrium-90-labelled ((90)Y) resin microspheres (SIR-Spheres; Sirtex Medical Limited, Sydney, Australia) as a single procedure on day 2 of the first weekly cycle of 5-fluorouracil (5FU; 600 mg/m(2)) with the option to switch to gemcitabine (1000 mg/m(2)) after 8 weeks of 5FU. Statistical analysis was conducted using Microsoft Excel (Microsoft Corporation, Redmond, Washington, USA).

The uptake of soluble and nanoparticulate imaging isotope in model liver tumours after intra-venous and intra-arterial administration.

Delivery of chemotherapeutic drugs to tumours by reformulation as nanoparticles has often been proposed as a means of facilitating increased selective uptake, exploiting the increased permeability of the tumour vasculature. However realisation of this improvement in drug delivery in cancer patients has met with limited success. We have compared tumour uptake of soluble Tc99m-pertechnetate and a colloid of nanoparticles with a Tc99m core, using both intra-venous and intra-arterial routes of administration in a rabbit liver VX2 tumour model.

Treatment of fluorouracil-refractory patients with liver metastases from colorectal cancer by using yttrium-90 resin microspheres plus concomitant systemic irinotecan chemotherapy.

Purpose: Liver metastases are the principal cause of death in patients with advanced colorectal cancer (CRC). Irinotecan is a chemotherapeutic agent used in the treatment of CRC and has demonstrated synergistic potential when used with radiation. Radioembolization with yttrium-90 microspheres has demonstrated increased response and survival rates when given with fluorouracil chemotherapy.

Toxicity of low dose azathioprine and 6-mercaptopurine in rat hepatocytes. Roles of xanthine oxidase and mitochondrial injury.

Background/aims: To study effects of pharmacologic concentrations of azathioprine and 6-mercaptopurine (6-MP) on rat hepatocytes.

Methods: Hepatocytes cultured on matrigel were incubated with azathioprine or 6-MP; effects of putative protective agents were studied. Viability (LDH leakage), reduced (GSH) and oxidized glutathione (GSSG), mitochondrial (mt) GSH, ATP and ultrastructural changes were determined.