Alexander J.B. McEwan

A prospective, randomised double-blind crossover study to examine the efficacy of strontium-89 in pain palliation in patients with advanced prostate cancer metastatic to bone

The palliative efficacy of strontium-89 chloride has been evaluated in a prospective double-blind crossover study comparing it with stable strontium as placebo in 32 patients with prostate cancer metastatic to bone. Response was assessed 5 weeks after each treatment. 26 patients were evaluable. Complete pain relief was only reported following strontium-89 injection. Statistical comparison between placebo and strontium-89 showed clear evidence of a therapeutic response to strontium-89 compared with only a limited placebo effect (P less than 0.01).

Enhancement of Radiation Cytotoxicity in Breast‐Cancer Cells by Localized Attachment of Gold Nanoparticles

Gold nanoparticles (GNPs) and modified GNPs having two kinds of functional molecules, cysteamine (AET) and thioglucose (Glu), are synthesized. Cell uptake and radiation cytotoxicity enhancement in a breast-cancer cell line (MCF-7) versus a nonmalignant breast-cell line (MCF-10A) are studied. Transmission electron microscopy (TEM) results show that cancer cells take up functional Glu-GNPs significantly more than naked GNPs. The TEM results also indicate that AET-capped GNPs are mostly bound to the MCF-7 cell membrane, while Glu-GNPs enter the cells and are distributed in the cytoplasm. After MCF-7 cell uptake of Glu-GNPs, or binding of AET-GNPs, the in vitro cytotoxicity effects are observed at 24, 48, and 72 hours. The results show that these functional GNPs have little or no toxicity to these cells. To validate the enhanced killing effect on cancer cells, various forms of radiation are applied such as 200 kVp X-rays and gamma-rays, to the cells, both with and without functional GNPs. By comparison with irradiation alone, the results show that GNPs significantly enhance cancer killing.

Strontium-89 chloride for pain palliation in prostatic skeletal malignancy

In a multi-centre study strontium-89 was shown to be effective in relieving bone pain from prostatic carcinoma in patients who had failed conventional therapies. Of 83 patients assessed at 3 months, following the administration of a dose of at least 1.5 MBq/kg, 75% derived benefit and 22% became pain free. Symptomatic improvement usually occurred within 6 weeks and continued for between 4 and 15 months (mean 6 months). Based on the dose estimation part of this study the recommended dose of strontium-89 is 150 MBq. Toxicity was low, provided platelet levels were above 100 x 10(9) l-1 at the time of treatment. Repeat treatments with strontium-89 may be given at intervals of not less than 3 months. Strontium-89 is administered intravenously on an out-patient basis with no special radiological protection precautions.

A retrospective analysis of the cost effectiveness of treatment with Metastron® (89sr-chloride) in patients with prostate cancer metastatic to bone

The objectives of the study were to estimate the cost of medical care for patients recruited into the Trans Canada trial of Metastron® (89Sr-chloride) as adjunct therapy in patients with prostate cancer metastatic to bone and to compare the costs of those receiving Metastron with those receiving placebo. Data from case report forms, hospital records and, where necessary, telephone follow-up were used. Twenty-nine patients, recruited into the trial at the Cross Cancer Institute, were followed from time of entry into the trial over the balance of their lifetime. Data were costed by reference to fee schedule, pharmacy and government and hospital defined costs as indirect (investigations, outpatient visits and total and tertiary hospital inpatient days) and direct (analgesics, hormones, radiotherapy and transfusions). Meaningful differences in analgesic, hormone and radiotherapy costs were seen between the two groups, with the group receiving Metastron showing a lifetime reduction of Can

A local contrast based approach to threshold segmentation for PET target volume delineation.

1720 per person when compared with placebo. A reduction of Can

Fluoroazomycin arabinoside (FAZA): synthesis, 2H and 3H‐labelling and preliminary biological evaluation of a novel 2‐nitroimidazole marker of tissue hypoxia

5696 per patient in the Metastron group was shown based upon requirements for admission for tertiary care; however, if total hospital stay costs are calculated there is no difference between the two groups. This retrospective study suggests that treatment with Metastron can bring about meaningful reductions in lifetime management costs in patients with advanced prostate cancer. These findings should be correlated with the significant improvement in quality of life reported in the Trans Canada study and appear to offer financial support to the clinical rationale for the use of Metastron in the palliative treatment of these patients.

Iterative threshold segmentation for PET target volume delineation.

Current radiation therapy techniques, such as intensity modulated radiation therapy and three-dimensional conformal radiotherapy rely on the precise delivery of high doses of radiation to well-defined volumes. CT, the imaging modality that is most commonly used to determine treatment volumes cannot, however, easily distinguish between cancerous and normal tissue. The ability of positron emission tomography (PET) to more readily differentiate between malignant and healthy tissues has generated great interest in using PET images to delineate target volumes for radiation treatment planning. At present the accurate geometric delineation of tumor volumes is a subject open to considerable interpretation. The possibility of using a local contrast based approach to threshold segmentation to accurately delineate PET target cross sections is investigated using well-defined cylindrical and spherical volumes. Contrast levels which yield correct volumetric quantification are found to be a function of the activity concentration ratio between target and background, target size, and slice location. Possibilities for clinical implementation are explored along with the limits posed by this form of segmentation.

Thresholding in PET images of static and moving targets

1-α-D-(5-Fluoro-5-deoxyarabinofuranosyl)-2-nitroimidazole (fluoroazomycin arabinoside, FAZA) 6, a putative PET imaging agent when labelled with 18F, was synthesized by fluorination of 1-α-D-(2,3-di-O-acetylarabinofuranosyl)-2-nitroimidazole 3 with DAST followed by deprotection. The C-5′-deuterated and tritiated analogues were prepared by NaCNBD3 or NaCNBT3 reduction of the protected C-5′-carbonyl intermediate 5, followed by C-5′ fluorination and deprotection, to afford C-5′ deuterated and C-5′ tritiated FAZA, respectively. Preliminary in vivo biodistribution studies in a murine tumour model, and pharmacokinetic studies in rats indicated that 3H-FAZA has biodistribution, tumour uptake and pharmacokinetic properties similar to those of 123I-IAZA, a clinically-proven radiopharmaceutical for SPECT-imaging of hypoxic tissues. Copyright

Biodistribution and Uptake of 3′-Deoxy-3′-Fluorothymidine in ENT1-Knockout Mice and in an ENT1-Knockdown Tumor Model

The purpose of this work is to create a rigorous method of segmenting PET images using an automated iterative technique. To this end a phantom study employing spherical targets was used to determine local (slice specific) threshold levels which produce correct cross-sections based on the contrast between target and background. Numerous target to background activity concentration ratios were investigated but found to have minimal effect in comparison to the influence of target size. Functions were fit to this data and used to construct an iterative threshold segmentation algorithm. In all cases this approach yielded convergence within ten iterations. Iterative threshold segmentation was applied using both an axial and tri-axial approach to the spherical targets and also to two irregularly shaped volumes. Of these two approaches, the tri-axial method proved less susceptible to image noise and better at dealing with partial volume effects at the interface between target and background. For comparative purposes, single thresholds of 28% and 40% were also applied to the spherical data sets. The tri-axial iterative method was found capable of delineating cross sections with areas greater than 250 mm2 to within the maximum resolution possible (1 pixel width). Cross sections of less than 250 mm2 in area were resolved by the tri-axial method to within 2 pixel widths of their true physical extent. Local contrast based iterative threshold segmentation shows promise as a method of rigorously delineating PET target volumes with good accuracy subject to the limitations imposed by the image resolution which currently characterizes this modality.

Comparison of three image segmentation techniques for target volume delineation in positron emission tomography.

Continued therapeutic gain in the treatment of non-small-cell lung cancer (NSCLC) will depend upon our ability to escalate the dose to the primary tumour while minimizing normal tissue toxicity. Both these objectives are facilitated by the accurate definition of a target volume that is as small as possible. To this end, both tumour immobilizations via deep inspiratory breath-hold, along with positron emission tomography (PET), have emerged as two promising approaches. Though PET is an excellent means of defining the general location of a tumour focus, its ability to define exactly the geometric extent of such a focus strongly depends upon selection of an appropriate image threshold. However, in clinical practice, the image threshold is typically not chosen according to consistent, well-established criteria. This study explores the relationship between image threshold and the resultant PET-defined volume using a series of F-18 radiotracer-filled hollow spheres of known internal volumes, both static and under oscillatory motion. The effects of both image threshold and tumour motion on the resultant PET image are examined. Imaging data are further collected from a series of simulated gated PET acquisitions in order to test the feasibility of a patient-controlled gating mechanism during deep inspiratory breath-hold. This study illustrates quantitatively considerable variability in resultant PET-defined tumour volumes depending upon numerous factors, including image threshold, size of the lesion, the presence of tumour motion and the scanning protocol. In this regard, when using PET in treatment planning for NSCLC, the radiation oncologist must select the image threshold very carefully to avoid either under-dosing the tumour or overdosing normal tissues.