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.

Multi institutional quantitative phantom study of yttrium-90 PET in PET/MRI: the MR-QUEST study.

Background: Yttrium-90 (Y) radioembolization involves the intra-arterial delivery of radioactive microspheres to treat hepatic malignancies. Though this therapy involves careful pre-treatment planning and imaging, little is known about the precise location of the microspheres once they are administered. Recently, there has been growing interest post-radioembolization imaging using positron-emission tomography (PET) for quantitative dosimetry and identifying lesions that may benefit from additional salvage therapy.

Phantom validation of quantitative Y-90 PET/CT-based dosimetry in liver radioembolization.

Background: PET/CT has recently been shown to be a viable alternative to traditional post-infusion imaging methods providing good quality images of Y-laden microspheres after selective internal radiation therapy (SIRT). In the present paper, first we assessed the quantitative accuracy of Y-PET using an anthropomorphic phantom provided with lungs, liver, spine, and a cylindrical homemade lesion located into the hepatic compartment. Then, we explored the accuracy of different computational approaches on dose calculation, including (I) direct Monte Carlo radiation transport using Raydose, (II) Kernel convolution using Philips Stratos, (III) local deposition algorithm, (IV) Monte Carlo technique (MCNP) considering a uniform activity distribution, and (V) MIRD (Medical Internal Radiation Dose) analytical approach.

Clinical and imaging-based prognostic factors in radioembolisation of liver metastases from colorectal cancer: a retrospective exploratory analysis.

Background: The aim of this study was to investigate the relationship between absorbed dose and response of colorectal cancer liver metastases treated with [Y]-resin microspheres and to explore possible clinical and imaging derived prognostic factors.

Methods: FDG PET/CT was used to measure response of individual lesions to a measured absorbed dose, derived from post-treatment Y PET imaging. Predicted dose was also derived from planning [Tc]-MAA SPECT data.

Abdo-Man: a 3D-printed anthropomorphic phantom for validating quantitative SIRT.

Background: The use of selective internal radiation therapy (SIRT) is rapidly increasing, and the need for quantification and dosimetry is becoming more widespread to facilitate treatment planning and verification. The aim of this project was to develop an anthropomorphic phantom that can be used as a validation tool for post-SIRT imaging and its application to dosimetry.

Method: The phantom design was based on anatomical data obtained from a T1-weighted volume-interpolated breath-hold examination (VIBE) on a Siemens Aera 1.

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).

A multicentre comparison of quantitative (90)Y PET/CT for dosimetric purposes after radioembolization with resin microspheres : The QUEST Phantom Study.

Purpose: To investigate and compare the quantitative accuracy of (90)Y imaging across different generation PET/CT scanners, for the purpose of dosimetry after radioembolization with resin microspheres.

Methods: A strict experimental and imaging protocol was followed by 47 international sites using the NEMA 2007/IEC 2008 PET body phantom with an 8-to-1 sphere-to-background ratio of (90)Y solution. The phantom was imaged over a 7-day period (activity ranging from 0.

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.

MRP2 (ABCC2) and cisplatin sensitivity in hepatocytes and human ovarian carcinoma.

Objective: The ABC transporter MRP2 (ABCC2) can mediate cisplatin efflux, and over-expression of MRP2 has been associated with cisplatin resistance in cancer cell lines. The aim of this study was to determine the role of MRP2 in modulating cisplatin cytotoxicity in normal cells as well as the relationship between MRP2 expression and clinical response to platinum-based agents in ovarian cancer.

Methods: The effect of absence of MRP2 expression on cisplatin sensitivity was investigated using primary hepatocyte cultures from the TR- rat strain, which is deficient in Mrp2.

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.