A phase I study of oral panobinostat alone and in combination with docetaxel in patients with castration-resistant prostate cancer.

Purpose: Histone deacetylase inhibitors have demonstrated anticancer activity against a range of tumors. We aimed to define the maximum tolerated dose, toxicity, activity, and pharmacokinetics of oral panobinostat, a pan-deacetylase inhibitor, alone and in combination with docetaxel for the treatment of castration-resistant prostate cancer (CRPC).

Methods: Sixteen patients were enrolled, eight in each arm.

Diffusion-weighted magnetic resonance imaging as a cancer biomarker: consensus and recommendations.

On May 3, 2008, a National Cancer Institute (NCI)-sponsored open consensus conference was held in Toronto, Ontario, Canada, during the 2008 International Society for Magnetic Resonance in Medicine Meeting. Approximately 100 experts and stakeholders summarized the current understanding of diffusion-weighted magnetic resonance imaging (DW-MRI) and reached consensus on the use of DW-MRI as a cancer imaging biomarker. DW-MRI should be tested as an imaging biomarker in the context of well-defined clinical trials, by adding DW-MRI to existing NCI-sponsored trials, particularly those with tissue sampling or survival indicators.

The role of clinical imaging in oncological drug development.

Clinical imaging has the potential to provide key biomarkers to inform decision-making in drug development. There is considerable optimism that emerging functional imaging techniques will substantially add to the conventional morphological depiction of disease. The discovery, development and qualification of clinical imaging biomarkers remain a considerable undertaking.

Molecular imaging in oncology.

Cancer is a genetic disease that manifests in loss of normal cellular homeostatic mechanisms. The biology and therapeutic modulation of neoplasia occurs at the molecular level. An understanding of these molecular processes is therefore required to develop novel prognostic and early biomarkers of response.

Pelvic phased-array MR imaging of anal carcinoma before and after chemoradiation.

The aim of this study was to evaluate the MR findings of anal carcinoma using an external pelvic phased-array coil before and after chemoradiation treatment. 15 patients with carcinoma of the anal canal underwent T(2) weighted and short-tau inversion recovery (STIR) imaging before and after chemoradiation. Images were reviewed in consensus by two radiologists.

Rectal carcinoma: MRI with histologic correlation before and after chemoradiation therapy.

Objective: The purpose of this study was to use MRI to compare the morphologic features of rectal cancer before and 6 weeks after chemotherapy and radiation treatment to correlate the posttreatment MRI appearances with the histologic findings in resected tumors.

Materials And Methods: High-resolution T2-weighted MRI was performed before and immediately after a standardized 5-week course of chemoradiation therapy in the care of 30 patients with locally advanced adenocarcinoma of the rectum. Changes in morphologic features were evaluated with respect to primary tumor and nodal downstaging.

Pelvic malignancy: integrating form and function.

Despite the essential role morphological imaging plays in the management of patients with malignancy, anatomical techniques are limited in their ability to report on tumour biology and behaviour. It has therefore been necessary to develop imaging techniques that integrate form and function to probe the micro and molecular environments of cancers. The role of clinical functional and molecular magnetic resonance imaging is discussed with an emphasis on pelvic malignancy.

Localized COSY and DQF-COSY 1H-MRS sequences for investigating human tibial bone marrow in vivo and initial application to patients with acute leukemia.

Purpose: To develop 2D 1H-MRS measurement sequences for the evaluation of bone marrow lipids, and to assess these measurement sequences in healthy and diseased bone marrow.

Materials And Methods: Single-voxel localized variants of COSY and DQF-COSY 2D 1H-MRS sequences were developed for use at 1.5 T to investigate the biochemical composition of human bone marrow in vivo.

Identification of biliary metabolites of ifosfamide using 31P magnetic resonance spectroscopy and mass spectrometry.

Biliary excretion is a significant component in the metabolism of many drugs, but remains difficult to detect and characterise non-invasively. A previous publication recently described the detection of metabolites of ifosfamide in gall bladder in a guinea pig model using in vivo 1H-decoupled 31P 3-D magnetic resonance spectroscopic imaging and a clinical 1.5 T MR scanner.

Quantitative assessment of the hepatic pharmacokinetics of the antimicrobial sitafloxacin in humans using in vivoF magnetic resonance spectroscopy.

Aims: To measure hepatic concentrations of the fluorine-containing antimicrobial, sitafloxacin, using in vivo(19)F magnetic resonance spectroscopy (MRS).

Methods: Data were acquired from eight healthy subjects at 2, 5, 8 and 24 h following doses of 500 mg day(-1) for 5 days using a (1)H/(19)F surface coil in a 1.5T clinical MR system.

Angiogenesis imaging in man: a personal view from the pharmaceutical industry.

The imaging of angiogenesis in human disease represents an exciting prospect for those involved in the drug development process. With an increasing focus on the therapeutic modulation of angiogenesis in man, the development of technologies capable of monitoring angiogenic drug interventions non-invasively should be welcomed.

Investigation of microenvironmental factors influencing the longitudinal relaxation times of drugs and other compounds.

The aim of this study was to investigate the microenvironmental factors likely to influence the longitudinal relaxation time of MR visible drugs or compounds in vivo at 1.5 T. The relative influence that viscosity, albumin and paramagnetic contrast agent concentrations have on the observed longitudinal relaxation times of three 19F MR detectable drugs and compounds have been investigated.

The development and application of functional nuclear magnetic resonance to in vivo therapeutic anticancer research: 2002 Sir Godfrey Hounsfield lecture delivered at the President's Day, Manchester.

A little over 30 years ago, Sir Godfrey Hounsfield and his colleagues revolutionized medical imaging by developing CT scanning. In recent years a combination of improved technology and a deeper understanding of tumour biology have led to the development of imaging based strategies aimed at interrogating tissue structure and function. The prospects of this new technology include the prediction of tumour response and the non-invasive study of conventionally inaccessible yet important pharmacological compartments.

Perfusion MR imaging of extracranial tumor angiogenesis.

Dynamic contrast-enhanced MRI (DCE-MRI) using small molecular weight gadolinium chelates enables noninvasive imaging characterization of tissue vascularity. Depending on the technique used, data reflecting tissue perfusion (blood flow, blood volume, mean transit time), microvessel permeability surface area product, and extracellular leakage space can be obtained. Insights into these physiological processes can be obtained from inspection of kinetic enhancement curves or by the application of complex compartmental modeling techniques.

Monitoring temozolomide treatment of low-grade glioma with proton magnetic resonance spectroscopy.

Assessment of low-grade glioma treatment response remains as much of a challenge as the treatment itself. Proton magnetic resonance spectroscopy ((1)H-MRS) and imaging were incorporated into a study of patients receiving temozolomide therapy for low-grade glioma in order to evaluate and monitor tumour metabolite and volume changes during treatment. Patients (n=12) received oral temozolomide (200 mg m(-2) day(-1)) over 5 days on a 28-day cycle for 12 cycles.

Human gallbladder bile: noninvasive investigation in vivo with single-voxel 1H MR spectroscopy.

Proton (hydrogen 1) magnetic resonance (MR) spectroscopy was used to study model and porcine bile in vitro. The method was subsequently developed to facilitate the acquisition of in vivo 1H MR spectra from the gallbladder bile of 10 human volunteers. Signals attributable to phosphotidylcholine and conjugated bile acid protons were observed in eight of the 10 volunteers.

Ifosfamide pharmacokinetics and hepatobiliary uptake in vivo investigated using single- and double-resonance 31P MRS.

MRS has considerable potential for the measurement of drug pharmacokinetics in vivo. In this study single- and double-resonance (31)P MRS was used to investigate the biodistribution, pharmacokinetics, and metabolism of ifosfamide following administration of 500 mg/kg ifosfamide in guinea pigs. (1)H-decoupling was found to nearly double the signal of detected peaks.

Non-invasive study of human gall bladder bile in vivo using (1)H-MR spectroscopy.

The sampling of gall bladder bile for analytical studies remains an invasive procedure. We demonstrate the application of the non-invasive methodology of (1)H-MR spectroscopy to the qualitative and quantitative assessment of human gall bladder bile in vivo. Spectral profiles in vivo are shown in relation to model and porcine gall bladder bile and the quantitation in man of the trimethylamine (choline) and lecithin concentrations were estimated to range from 25.

Could assessment of glioma methylene lipid resonance by in vivo (1)H-MRS be of clinical value?

The potential clinical role of in vivo (1)H-MRS ((1)H-magnetic resonance spectroscopy) lipid methylene resonance measurements of human glioma has been assessed. 20 patients, 14 with low grade and 6 with high grade gliomas have been investigated using single voxel (1)H-MRS. Three of the low grade group had undergone transformation by clinical and imaging criteria.

Diffusion MRI for prediction of response of rectal cancer to chemoradiation.

Prediction of tumour response before onset of treatment could have considerable clinical benefit. Since the apparent diffusion coefficient (ADC) of a tumour's water content can show the extent of necrosis, we looked for a possible correlation of ADC with response to treatment. We measured mean tumour water ADC before and after chemotherapy and chemoradiation in 14 patients with locally advanced rectal cancer, with a quantitative magnetic resonance diffusion imaging sequence.