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Biomedical subjects

Pat Price

Publications and source records attributed to Pat Price.

At least 19 recordsLinked to original sources
PubMed2006

Online adaptive radiotherapy of the bladder: small bowel irradiated-volume reduction.

PURPOSE: To assess the potential reduction of small bowel volume receiving high-dose radiation by using kilovoltage X-ray cone beam computed tomography (CBCT) and quantized margin selection for adaptive bladder cancer treatment. METHODS AND MATERIALS: Twenty bladder patients were planned conformally using a four-field, 15-mm uniform margin technique. Two additional planning target volumes (PTVs) were created using margins quantized to 5 and 10 mm in the superior direction only. CBCTs (approximately 8 scans/patient) were acquired during treatment. CBCT volumes were registered with CT planning scans to determine setup errors and to select the appropriate PTV of the day. Margin reduction in other directions was considered. Outlining of small bowel in every fraction is required to properly quantify the volume of small bowel spared from high doses. In the case of CBCT this is not always possible owing to artifacts created by small bowel movement and the presence of gas. A simpler method was adopted by considering the volume difference between PTVs created using uniform and adapted margins, which corresponds to the potential volume of small bowel sparing. RESULTS: The average small bowel volume that can be spared by this form of adaptive radiotherapy is 31 +/- 23 cm3 (+/-1 SD). The bladder for 1 patient was systematically smaller than the planning scan and hence demonstrated the largest average reduction of 76 cm3. The clinical target volume to PTV margins in other directions can be safely reduced to 10 mm except in the anterior direction where, like the superior direction, the bladder showed significant variation. CONCLUSIONS: Online CBCT-assisted plan selection based on quantized margins can significantly reduce the volume of small bowel receiving high doses for some bladder patients. CBCT allows the 15-mm margins used in some directions to be safely reduced to 10 mm.

Humans↗
PubMed2006

Early change in glucose metabolic rate measured using FDG-PET in patients with high-grade glioma predicts response to temozolomide but not temozolomide plus radiotherapy.

PURPOSE: To compare the ability of positron emission tomography (PET) to predict response to temozolomide vs. temozolomide plus radiotherapy. METHODS AND MATERIALS: Nineteen patients with high-grade glioma (HGG) were studied. Patients with recurrent glioma received temozolomide 75 mg/m2 daily for 7 weeks (n=8). Newly diagnosed patients received temozolomide 75 mg/m2 daily plus radiotherapy 60 Gy/30 fractions over 6 weeks, followed by six cycles of adjuvant temozolomide 200 mg/m2/day (Days 1-5 q28) starting 1 month after radiotherapy (n=11). [18F]Fluorodeoxyglucose ([18F]FDG) PET scan and magnetic resonance imaging (MRI) were performed at baseline, and 7 and 19 weeks after initiation of temozolomide administration. Changes in glucose metabolic rate (MRGlu) and MRI response were correlated with patient survival. RESULTS: In the temozolomide-alone group, patients who survived>26 vs. or=25%, survived longer than nonresponders with mean survival times of 75 weeks (95% CI, 34-115 vs. 20 weeks (95% CI, 14-26) (p=0.0067). In the small group of patients studied, there was no relationship between MRI response and survival (p=0.52). For patients receiving temozolomide plus radiotherapy, there was no difference in survival between PET responders and nonresponders (p=0.32). CONCLUSIONS: Early changes in MRGlu predict response to temozolomide, but not temozolomide plus radiotherapy.

Adolescent↗
PubMed2006

Clinical molecular imaging with positron emission tomography.

Molecular imaging allows for the in vivo evaluation of targeted molecules and biological processes in man. Positron emission tomography (PET) is a highly sensitive and quantitative molecular imaging modality, whose utility in clinical and experimental medicine is increasing by the day. In this article, the principles of PET and its currently accepted applications in oncology, such as cancer staging, treatment response assessment and as a prognostic marker are reviewed. Further, the evolving role of PET in areas of oncology such as radiotherapy treatment planning, anti-cancer drug development and the evaluation of patho-physiological processes which drive a cell into neoplastic activity is discussed.

Antineoplastic Agents↗
PubMed2006

X-ray volume imaging in bladder radiotherapy verification.

PURPOSE: To assess the clinical utility of X-ray volume imaging (XVI) for verification of bladder radiotherapy and to quantify geometric error in bladder radiotherapy delivery. METHODS AND MATERIALS: Twenty subjects undergoing conformal bladder radiotherapy were recruited. X-ray volume images and electronic portal images (EPIs) were acquired for the first 5 fractions and then once weekly. X-ray volume images were co-registered with the planning computed tomography scan and clinical target volume coverage assessed in three dimensions (3D). Interfraction bladder volume change was described by quantifying changes in bladder volume with time. Bony setup errors were compared from both XVI and EPI. RESULTS: The bladder boundary was clearly visible on coronal XVI views in nearly all images, allowing accurate 3D treatment verification. In 93.5% of imaged fractions, the clinical target volume was within the planning target volume. Most subjects displayed consistent bladder volumes, but 25% displayed changes that could be predicted from the first three XVIs. Bony setup errors were similar whether calculated from XVI or EPI. CONCLUSIONS: Coronal XVI can be used to verify 3D bladder radiotherapy delivery. Image-guided interventions to reduce geographic miss and normal tissue toxicity are feasible with this technology.

Aged↗
PubMed2005

X-ray volumetric imaging in image-guided radiotherapy: the new standard in on-treatment imaging.

PURPOSE: X-ray volumetric imaging (XVI) for the first time allows for the on-treatment acquisition of three-dimensional (3D) kV cone beam computed tomography (CT) images. Clinical imaging using the Synergy System (Elekta, Crawley, UK) commenced in July 2003. This study evaluated image quality and dose delivered and assessed clinical utility for treatment verification at a range of anatomic sites. METHODS AND MATERIALS: Single XVIs were acquired from 30 patients undergoing radiotherapy for tumors at 10 different anatomic sites. Patients were imaged in their setup position. Radiation doses received were measured using TLDs on the skin surface. The utility of XVI in verifying target volume coverage was qualitatively assessed by experienced clinicians. RESULTS: X-ray volumetric imaging acquisition was completed in the treatment position at all anatomic sites. At sites where a full gantry rotation was not possible, XVIs were reconstructed from projection images acquired from partial rotations. Soft-tissue definition of organ boundaries allowed direct assessment of 3D target volume coverage at all sites. Individual image quality depended on both imaging parameters and patient characteristics. Radiation dose ranged from 0.003 Gy in the head to 0.03 Gy in the pelvis. CONCLUSIONS: On-treatment XVI provided 3D verification images with soft-tissue definition at all anatomic sites at acceptably low radiation doses. This technology sets a new standard in treatment verification and will facilitate novel adaptive radiotherapy techniques.

Abdominal Neoplasms↗
PubMed2005

2-[11C]thymidine positron emission tomography reproducibility in humans.

PURPOSE: To evaluate the reproducibility of 2-[11C]thymidine positron emission tomography (PET) scanning in patients with advanced intra-abdominal malignancies. PATIENTS AND METHODS: The reproducibility of 2-[11C]thymidine PET was studied by comparing interpatient and intrapatient variability (coefficient of variability, COV) of both blood and tissue data. Arterial plasma metabolite levels were measured using on-line sampling and high-pressure liquid chromatography. 2-[11C]Thymidine retention in tissue was measured as the standardized uptake value at the end of the scan (SUV(end)), the area under the time-activity curve (AUC(0-1 hour)), and the fractional retention of thymidine (FRT). A group of seven patients were scanned 1 week apart with no intervening anticancer therapy. RESULTS: There was interpatient variability in the levels of 2-[11C]thymidine and its main metabolite, 11CO2, in plasma. Variability in 2-[11C]thymidine PET data was greater between (COV: SUV(end) = 38%, AUC(0-1 hour) = 32%, FRT = 47%) than within (COV: SUV(end) = 8%, AUC(0-1 hour) = 2%, FRT = 9%) patients. There was a borderline significant difference between the paired tumor data for SUV(end) (P = 0.041), but not for AUC(0-1 hour) (P = 0.81) or FRT (P = 0.90). There was a good correlation between paired data for SUV(end) (r = 0.98), AUC(0-1 hour) (r = 0.99), and FRT (r = 0.95). CONCLUSIONS: This is the first report showing that 2-[11C]thymidine PET scanning is reproducible in humans. Repeat scanning of tumor proliferation using 2-[11C]thymidine PET is feasible to perform in human intra-abdominal malignancies and should aid the future rapid assessment of antiproliferative tumor agents.

Abdominal Neoplasms↗
PubMed2004

Measuring tumor pharmacodynamic response using PET proliferation probes: the case for 2-[(11)C]-thymidine.

[(18)F]-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) is becoming accepted as a diagnostic tool for cancer, but the potential uses of PET in oncology extend beyond the imaging of glucose metabolism. The development of a PET proliferation probe would be a useful pharmacodynamic tool. [(11)C]-thymidine PET has been assessed in man as a specific measure of tumor proliferation. Uptake of [(11)C]-thymidine is related to DNA synthesis and, in human tumors, correlates with proliferation. When compared with (18)F-FDG, it has been shown to be a more sensitive discriminator of early clinical tumor response. 2-[(11)C]-thymidine PET scanning of patients enrolled in early phase clinical trials is feasible and should support future drug development. Although recent research is moving away from the validation of thymidine towards thymidine analogues radiolabeled with (18)F, the better specificity of thymidine for DNA should be the rationale for its continued development and application as a PET probe. This review describes the historical development, application and current research status of [(11)C]-thymidine PET, and aims to highlight the need for its continuing development as a marker of tumor proliferation.

Carbon Radioisotopes↗
PubMed2004

Trans-perineal implantation of radio-opaque treatment verification markers into the prostate: an assessment of procedure related morbidity, patient acceptability and accuracy.

On-line imaging of prostate markers can be used to compensate for errors in radiation delivery. This study assessed the patient acceptability and morbidity associated with the trans-perineal route of implantation. A minority experienced acute pain or bleeding. Placement was accurate in all but one subject. An operator related learning curve exists. Although this is an invasive procedure most patients found it acceptable. Implementation for routine clinical practice is feasible.

Adenocarcinoma↗
PubMed2004

Combretastatin A4 phosphate.

Combretastatin A4 phosphate (CA4P) is a water-soluble prodrug of combretastatin A4 (CA4). The vascular targeting agent CA4 is a microtubule depolymerizing agent. The mechanism of action of the drug is thought to involve the binding of CA4 to tubulin leading to cytoskeletal and then morphological changes in endothelial cells. These changes increase vascular permeability and disrupt tumor blood flow. In experimental tumors, anti-vascular effects are seen within minutes of drug administration and rapidly lead to extensive ischemic necrosis in areas that are often resistant to conventional anti-cancer treatments. Following single-dose administration a viable tumor rim typically remains from which tumor regrowth occurs. When given in combination with therapies targeted at the proliferating viable rim, enhanced tumor responses are seen and in some cases cures. Results from the first clinical trials have shown that CA4P monotherapy is safe and reduces tumor blood flow. There has been some promising demonstration of efficacy. CA4P in combination with cisplatin is also safe. Functional imaging studies have been used to aid the selection of doses for phase II trials. Both dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and positron emission tomography can measure the anti-vascular effects of CA4P in humans. This review describes the background to the development of CA4P, its proposed mechanism of action, the results from the first clinical trials with CA4P and the role of imaging techniques in its clinical development.

Animals↗
PubMed2003

Assessment of inter- and intrapatient variability in C15O2 positron emission tomography measurements of blood flow in patients with intra-abdominal cancers.

PURPOSE: The aim of the study was to evaluate the inter- and intrapatient variability of positron emission tomography (PET) measurements of perfusion in advanced solid cancers. EXPERIMENTAL DESIGN: Thirty-seven patients with predominantly intra-abdominal tumors underwent PET imaging using inhaled C15O2. Repeat data were obtained by scanning five patients twice, 1 week apart, with no intervening therapy. Regional flow and the volume of distribution (V(d)) were measured from dynamic images by use of a one-compartment model. Inter- and intrapatient variability were measured as the coefficient of variability (CV). Data were also obtained for regions of interest in normal liver, spleen, and kidney. RESULTS: The mean (+/-SD) regional flow in the tumors was 0.46 +/- 0.19 ml(blood)/min/ml(tissue), and the mean V(d) was 0.74 +/- 0.15 ml(blood)/ml(tissue). Variability in tumor flow was greater between (n = 37; CV = 41%) than within (n = 5; CV = 11%) patients. Variability in tumor V(d) was greater between (CV = 21%) than within (CV = 6%) patients. There was a good correlation between the repeat tumor data for both regional flow (rho = 0.82; P = 0.023) and V(d) (rho = 0.89; P = 0.007). Normal tissue variability was also greater between than within patients. In all cases, no statistically significant differences were seen between repeat measurements in the same patient. CONCLUSIONS: Dynamic C15O2 PET measurements of regional flow are reproducible in patients with predominantly intra-abdominal malignancies and may be useful for the pharmacodynamic evaluation of novel antivascular and antiangiogenic cancer therapeutic agents.

Abdominal Neoplasms↗
PubMed2003

Metabolic activation of temozolomide measured in vivo using positron emission tomography.

The purpose of this research was to quantitate and confirm the mechanism of in vivo metabolic activation of temozolomide. The secondary aims were to evaluate the tumor, normal tissue, and plasma pharmacokinetics of temozolomide in vivo, and to determine whether such pharmacokinetics resulted in tumor targeting. [(11)C]temozolomide kinetics were studied in men using positron emission tomography (PET). It has been postulated that temozolomide undergoes decarboxylation and ring opening in the 3-4 position to produce the highly reactive methyldiazonium ion that alkylates DNA. To investigate this, a dual radiolabeling strategy, with [(11)C]temozolomide separately radiolabelled in the 3-N-methyl and 4-carbonyl positions, was used. We hypothesized that (11)C in the C-4 position of [4-(11)C-carbonyl]temozolomide would be converted to [(11)C]CO(2) if the postulated mechanism of metabolic conversion was true resulting in lower [(11)C]temozolomide tumor exposure. Paired studies were performed with both forms of [(11)C]temozolomide in 6 patients with gliomas. Another PET scan with (11)C-radiolabelled bicarbonate was performed and used to account for the metabolites of temozolomide using a data-led analytical approach. Plasma was analyzed for [(11)C]temozolomide and [(11)C]metabolites throughout the scan duration. Exhaled air was also sampled throughout the scan for [(11)C]CO(2). The percentage ring opening of temozolomide over 90 min was also calculated to evaluate whether there was a differential in metabolic breakdown among plasma, normal tissue, and tumor. There was rapid systemic clearance of both radiolabelled forms of [(11)C]temozolomide over 90 min (0.2 liter/min/m(2)), with [(11)C]CO(2) being the primary elimination product. Plasma [(11)C]CO(2) was present in all of the studies with [4-(11)C-carbonyl]temozolomide and in half the studies with [3-N-(11)C-methyl]temozolomide. The mean contributions to total plasma activity by [(11)C]CO(2) at 10 and 90 min were 12% and 28% with [4-(11)C-carbonyl]temozolomide, and 1% and 4% with [3-N-(11)C-methyl]temozolomide, respectively. There was a 5-fold increase in exhaled [(11)C]CO(2) sampled with [4-(11)C-carbonyl]temozolomide compared with [3-N-(11)C-methyl]temozolomide (P < 0.05). A decrease in tissue exposure [area under the curve between 0 and 90 min (AUC(0-90 min))] to [(11)C]temozolomide was also observed with [4-(11)C-carbonyl] temozolomide compared with [3-N-(11)C-methyl]temozolomide. Of potential therapeutic advantage was the higher [(11)C]radiotracer and [(11)C]temozolomide exposure (AUC(0-90 min)) in tumors compared with normal tissue. [(11)C]temozolomide ring opening over 90 min was less in plasma (20.9%; P < 0.05) compared with tumor (26.8%), gray matter (29.7%), and white matter (30.1%), with no differences (P > 0.05) between tumor and normal tissues. The significantly higher amounts of [(11)C]CO(2) sampled in plasma and exhaled air, in addition to the lower normal tissue and tumor [(11)C]temozolomide AUC(0-90 min) observed with [4-(11)C-carbonyl]temozolomide, confirmed the postulated mechanism of metabolic activation of temozolomide. A higher tumor [(11)C]temozolomide AUC(0-90 min) in tumors compared with normal tissue and the tissue-directed metabolic activation of temozolomide may confer potential therapeutic advantage in the activity of this agent. This is the first report of a clinical PET study used to quantify and confirm the in vivo mechanism of metabolic activation of a drug.

Adult↗
PubMed2003

Iodine-124 labelled annexin-V as a potential radiotracer to study apoptosis using positron emission tomography.

Annexin-V is a calcium-dependent protein that binds with high affinity to phosphaditylserine exposed during apoptosis. The aim of this study was to radiolabel annexin-V with iodine-124 for use as a potential probe of apoptosis by positron emission tomography. Annexin-V was radioiodinated directly using the cyclotron-produced positron emitter iodine-124 by the chloramine-T (CAT) method and indirectly by the pre-labelled reagent N-succinimidyl 3-[124I]iodobenzoate ([124I]m-SIB). Some reaction parameters of the CAT method such as reaction time and pH were optimised to give radiochemical yields of 22.3 +/- 2.6%(n = 3, gel-filtration). After incubation with [124I]m-SIB, radiolabelled annexin-V was obtained in 14% and 25% yield by FPLC and gel-filtration, respectively. The radiochemical purities from direct and indirect labelling were 97.7 +/- 1.0%(n = 3) and 96.7 +/- 2.1%(n = 3), respectively. The new radiotracers could be stored for up to four days without significant de-iodination. The biological activity of radiolabelled annexin-V was tested in control and camptothecin-treated (i.e. apoptotic) human leukaemic HL60 cells. A significantly higher (21%) binding in treated cells was observed with [125I]m-SIB-annexin-V. The binding of [125I]m-SIB labelled annexin-V to camptothecin treated cells was blocked (68%) by a 100-fold excess of unlabelled annexin-V.

Annexin A5↗