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P J Ell

Publications and source records attributed to P J Ell.

At least 55 records · Page 3Linked to original sources

Positron emission tomography and colorectal cancer.

BACKGROUND: The oncological applications of positron emission tomography (PET) have gained widespread acceptance. This rapidly evolving technology has been applied successfully to colorectal cancer, but has not yet become part of routine clinical practice. This review considers (1) the biological basis for the use of PET in colorectal cancer, (2) the technical aspects of PET relevant to the referring clinician and (3) the application of PET to the management of primary and recurrent disease. METHODS: A Medline database search was performed for the period 1980-2000. Experience was also drawn from the first 40 patients with colorectal cancer investigated at this institution. RESULTS AND CONCLUSION: PET has a proven role, and is cost effective in the management of recurrent cancer and the monitoring of therapy. However, further evaluation is still required to justify its routine use for other indications in colorectal cancer. Development of new positron-labelled radio- pharmaceuticals, in parallel with advances in detector technology and innovative models for tracer production and distribution, means that the availability of PET and its applications in the management of colorectal cancer will expand over the coming years.

Colorectal Neoplasms↗

The role of [18F]fluoro-2-deoxyglucose-PET scanning in the diagnosis of paraneoplastic neurological disorders.

The detection of an occult tumour in a patient with a suspected paraneoplastic neurological disorder (PND) may be difficult because of the limitations of conventional imaging techniques. [(18)F]fluoro-2-deoxyglucose-PET (FDG-PET) can visualize a small tumour anywhere within the body. We retrospectively reviewed the case notes of 43 unselected patients with suspected PND referred for FDG-PET scanning to determine how useful this technique was when conventional imaging was negative. All patients had undergone standard radiological investigations and bronchoscopy (where appropriate) prior to PET scanning. There were discrete areas of hypermetabolism suggestive of malignancy (positive) in 16 patients (37%). A tissue diagnosis of cancer was subsequently made in seven patients (two at post-mortem), further radiological studies were suggestive of cancer in one patient, one patient subsequently presented with a metastatic deposit which was biopsied, and four patients died shortly afterwards without a post-mortem. In three patients, subsequent investigations were negative for cancer. Serum anti-neuronal antibodies were present in 43% and CSF oligoclonal bands were present in 46% of patients with positive PET scans compared with 16 and 26%, respectively, in PET-negative patients, but this was not significant. Only one patient with a negative scan has been diagnosed subsequently as having malignancy on prolonged follow-up. These findings confirm that FDG-PET scanning is a useful technique in the detection of small tumours in patients with suspected PND. False positives and false negatives do occur, but at a sufficiently low frequency to justify the clinical usefulness of this technique.

Adult↗

Functional imaging as an aid to decision-making in metastatic paraganglioma.

Malignant paraganglioma is a rare and slow growing tumour of neuroendocrine origin. At the time of diagnosis, the tumour is usually widespread, with limited therapeutic options. A variety of functional imaging studies are available for staging the disease, guiding therapy and monitoring treatment response. These include 123I-MIBG or 131I-MIBG, 111In-pentetreotide or 111In-lanreotide (somatostatin analogues), and 18F-FDG positron emission tomography. Various radionuclides, including 131I and 90Y, can be targeted to the tumour using MIBG or pentetreotide. Such targeted radionuclide therapy may provide valuable long-term palliation in such patients. We present two cases with metastatic paragangliomas who had widespread soft tissue and bone metastases. One patient was treatment naive and the second had received previous chemotherapy. The functional imaging work-up performed and the targeted radionuclide therapies considered in these patients are described. Both patients were treated with 131I-MIBG. Partial tumour response and complete symptomatic and hormonal response was achieved in one patient; in the second patient there was no change.

3-Iodobenzylguanidine↗

Influence of OSEM and segmented attenuation correction in the calculation of standardised uptake values for [18F]FDG PET.

Standardised Uptake Values (SUVs) are widely used in positron emission tomography (PET) as a semi-quantitative index of fluorine-18 labelled fluorodeoxyglucose uptake. The objective of this study was to investigate any bias introduced in the calculation of SUVs as a result of employing ordered subsets-expectation maximisation (OSEM) image reconstruction and segmented attenuation correction (SAC). Variable emission and transmission time durations were investigated. Both a phantom and a clinical evaluation of the bias were carried out. The software implemented in the GE Advance PET scanner was used. Phantom studies simulating tumour imaging conditions were performed. Since a variable count rate may influence the results obtained using OSEM, similar acquisitions were performed at total count rates of 34 kcps and 12 kcps. Clinical data consisted of 100 patient studies. Emission datasets of 5 and 15 min duration were combined with 15-, 3-, 2- and 1-min transmission datasets for the reconstruction of both phantom and patient studies. Two SUVs were estimated using the average (SUVavg) and the maximum (SUVmax) count density from regions of interest placed well inside structures of interest. The percentage bias of these SUVs compared with the values obtained using a reference image was calculated. The reference image was considered to be the one produced by filtered back-projection (FBP) image reconstruction with measured attenuation correction using the 15-min emission and transmission datasets for each phantom and patient study. A bias of 5%-20% was found for the SUVavg and SUVmax in the case of FBP with SAC using variable transmission times. In the case of OSEM with SAC, the bias increased to 10%-30%. An overall increase of 5%-10% was observed with the use of SUVmax. The 5-min emission dataset led to an increase in the bias of 25%-100%, with the larger increase recorded for the SUVmax. The results suggest that OSEM and SAC with 3 and 2 min transmission may be reliably used to reduce the overall data acquisition time without compromising the accuracy of SUVs.

Fluorodeoxyglucose F18↗

Optimal nuclear medicine support in sentinel node detection.

The correct identification of sentinel lymph nodes (SLNs) is paramount if this technique is to become the standard of care in the management of early disease in surgical oncology. Despite the apparent attraction and ease of this approach, a detailed understanding of its different technical components is vital. High sensitivity, reproducibility, and accuracy levels must be achieved in the identification and discrimination of the SLN if the extent and place of the standard lymph node diagnostic dissections can be challenged. This article reviews the technology and methodology and gives indications of the possible progress to be achieved.

Gamma Cameras↗

The clinical application of positron emission tomography to colorectal cancer management.

Colorectal cancer (CRC) is the second commonest cancer in the Western World. Successful treatment relies significantly on accurate detection and staging of primary disease as well as the early identification of the presence and extent of recurrence. Morphological imaging techniques, particularly computed tomography (CT), are well established and widely available to carry out these tasks in addition to predicting and monitoring response to therapy. This review analyses the current inadequacies for imaging CRC and critically assesses the potential role of functional imaging with positron emission tomography (PET). We review the current literature, use our experience from the first 1000 PET studies carried out at our Institution and the perspective of surgical colleagues. We find little evidence for the use of 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-PET for screening asymptomatic individuals and current modalities appear better suited for detection of symptomatic primary CRC. There is evidence of increased accuracy for FDG-PET in staging primary disease, but this area remains controversial and larger studies are necessary. The situation is quite the reverse with respect to imaging suspected recurrent disease with FDG-PET being more sensitive and specific than conventional techniques. This benefit manifests itself through alteration in patient management and results in cost savings. PET also appears to have a specific place in the evaluation of patients undergoing radiotherapy and chemotherapy, a role that will expand. The evidence suggests that PET will ultimately become routinely incorporated into CRC patient management algorithms. Technological advances coupled with novel tracer research will facilitate this.

Colorectal Neoplasms↗

Striatal and temporal cortical D2/D3 receptor occupancy by olanzapine and sertindole in vivo: a [123I]epidepride single photon emission tomography (SPET) study.

RATIONALE: Previous work suggests clozapine preferentially targets limbic cortical dopamine systems, which could help account for its lack of extrapyramidal side effects (EPS) and superior therapeutic efficacy. OBJECTIVES: To test the hypothesis that olanzapine, a novel atypical antipsychotic drug, occupies temporal cortical D2/D3 receptors to a greater extent than striatal D2/D3 receptors in vivo. METHODS: Nine schizophrenic patients taking either olanzapine [(n=5; mean (SD) age: 32.5 (6.5) years; daily dose: 18.3 (2.6) mg] or sertindole [(n=4; mean (SD) age: 30.3 (7.4) years; daily dose: 16 (5.6) mg] were studied with [123I]epidepride ((S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2,3-dimethoxybenz amide) and single photon emission tomography (SPET). An estimate of [123I]epidepride 'specific binding' to D2/D3 receptors was obtained in patients and age-matched healthy volunteers. A summary measure was generated representing striatal and temporal cortical relative %D2/D3 receptor occupancy by antipsychotic drugs. Occupancy data were compared with previously studied groups of patients receiving typical antipsychotic drugs (n=12) and clozapine (n=10). RESULTS: Mean striatal and temporal cortical %D2/D3 receptor occupancy in olanzapine-treated patients was 41.3% (SD 17.9) and 82.8% (SD 4.2), respectively. Unexpectedly low levels of striatal relative %D2/D3 receptor occupancy were seen in two patients with typical antipsychotic-drug-induced movement disorder prior to switching to olanzapine. In the temporal cortex, mean D2/D3 dopamine receptor occupancy levels above 80% were seen for all antipsychotic drugs studied. CONCLUSIONS: The atypical antipsychotic drugs olanzapine and sertindole, in common with clozapine, demonstrate higher occupancy of temporal cortical than striatal D2/D3 dopamine receptors in vivo at clinically useful doses. This could help mediate their atypical clinical profile of therapeutic efficacy with few extrapyramidal side effects. Limbic selective blockade of D2/D3 dopamine receptors could be a common action of atypical antipsychotic drugs.

Adult↗

Influence of arm positioning on tomographic thallium-201 myocardial perfusion imaging and the effect of attenuation correction.

Lateral attenuation in single-photon emission tomography (SPET) myocardial perfusion imaging (MPI) has been attributed to the left arm if it is held by the patient's side during data acquisition. As a result MPI data are conventionally acquired with the arms held above the head. The aims of this study were to determine the effect of imaging arms down on reconstructed tomographic images depicting regional myocardial thallium-201 distribution and to assess whether attenuation-corrected (AC) myocardial perfusion images acquired arms down could replace uncorrected (NC) images acquired arms up for routine clinical service. Twenty-eight patients referred for routine MPI underwent sequential 180 degrees emission/transmission imaging for attenuation correction using an L-shaped dual-headed gamma camera (GE Optima) fitted with two gadolinium-153 scanning line sources. Delay data were acquired twice: once supine with the arms up and then supine with the arms down. Detector radius of rotation (ROR) for arms up and arms-down studies was recorded. For each data set, count density was measured in 17 segments of a polar plot and segmental uptake expressed relative to study maximum. Oblique images were assessed qualitatively by two observers blinded to study type for tracer distribution and overall quality. Transmission maps were assessed for truncation. Mean detector ROR was 190 mm for arms-up studies and 232 mm for arms-down studies (P<0.05). Population mean segmental relative uptake values for NC arms-up studies were higher than for NC arms-down studies, with the greatest difference seen anterolaterally. Nevertheless, the majority (24/28) of oblique NC arms-up and NC arms-down images appeared similar and only four (14%) NC arms-down studies showed additional areas of reduced count density (one anterior and three lateral). Corresponding AC arms-down studies showed that count density within the anterior defect improved to normal but the lateral reductions persisted, and in two of these three studies the arms-down transmission map was distorted. Population mean segmental relative uptake values for NC arms-down studies were lower than for AC arms-down studies apart from three anterolateral segments where NC arms-down values were higher. Of 28 AC arms-down studies, 11 (39%) were of reduced quality compared with NC arms-up studies because of poorer spatial resolution and because AC enhances liver activity compared with NC. It is concluded that arm positioning influences reconstructed tomographic images depicting regional 201T1 distribution, particularly anterolaterally. There is lateral undercorrection in approximately 10% of AC arms-down studies, possibly because of attenuation map truncation. Image quality is reduced in about one-third of AC armsdown studies compared with NC arms-up studies. These data suggest that this attenuation correction method is not sufficiently robust to allow routine acquisition of MPI data with the arms down.

Adult↗

Radiation safety of the sentinel lymph node technique in breast cancer.

Many publications attest to the potential of the sentinel lymph node technique in advancing the clinical management of melanoma and, more recently, breast cancer. Whilst not yet universally regarded as the standard of care, the technique is gaining wide acceptance. Use of a radiolabelled colloidal tracer is central to optimising sensitivity, and this brings with it the need to address radiation safety issues relating to the use of radioactive materials in the operating theatre and pathology laboratory, and the generation of radioactive waste. The radiation dose to the patient should also be determined if the professional is to reassure the patient by placing this in its proper context. For the purpose of this investigation, biodistribution data were obtained from patient studies to quantify the migration of tracer beyond the injection site, thereby permitting a detailed assessment of the internal dosimetry of the tracer and the resulting radiation dose to the patient. Uptake of tracer in the sentinel nodes, reticulo-endothelial system and circulating blood was investigated. The radiation dose to surgical staff was recorded using whole-body monitors and extremity dosimeters worn at the fingers. Clinical waste in the operating theatre was monitored and the radioactive content of significantly contaminated items determined. The radiation dose to pathology staff was estimated from knowledge of the radioactive content of the specimens obtained and a study of work practices. Migration of tracer was found to be minimal, with greater than 95% retention at the injection site. The effective dose resulting to the patient was 2.1x10(-2) mSv/MBq, with a mean breast dose of 7.2x10(-1) mGy/MBq. A mean whole-body dose of 0.34 microSv was received by surgical staff per procedure, with a mean finger dose of 0.09 mSv (90 microSv). Radiation doses received by pathology staff will be predominantly below measurable levels and are likely to be negligible unless primary specimens from a large number of studies are analysed promptly upon their excision. At operation, surgical swabs can become significantly contaminated and have been found to contain up to 22% of the administered activity, dependent upon the surgical procedure performed. It is concluded that moderate activities of technetium-99m labelled tracer are administered to the patient, and the radiation risk to the patient is consequently low relative to that from many other medical exposures. The radiation doses to staff groups involved in all aspects of the technique are low, and under normal circumstances and levels of workload, routine radiation monitoring will not be required. Standard biohazard precautions prevent direct intake of radioactive contamination. Radioactive waste is created in the operating theatre, and may be generated in the pathology laboratory if specimens are not routinely stored until fully decayed. This will require special handling if the disposal of radioactive material is not permitted.

Breast Neoplasms↗

Impact of European societies on nuclear medicine.

The development of nuclear medicine in Europe began in the late 1940s and early 1950s. The supply of radionuclides was initially restricted, but slowly a number of hospital departments and universities gained access to these materials. From the beginning there was a strong international presence, and communication among scientists and doctors flourished rapidly. The need for national and later international nuclear medicine gatherings became apparent, and there soon emerged a number of prominent organizations. This article describes some of the historic developments that led to the formation of a single European Association of Nuclear Medicine-the EANM.

Europe↗

Striatal and extra-striatal D(2)/D(3) dopamine receptor occupancy by quetiapine in vivo. [(123)I]-epidepride single photon emission tomography(SPET) study.

BACKGROUND: Selective action at limbic cortical dopamine D(2)-like receptors could mediate atypical antipsychotic efficacy with few extrapyramidal side-effects. AIMS: To test the hypothesis that quetiapine has 'limbic selective' D(2)/D(3) receptor occupancy in vivo. METHOD: The high-affinity D(2)/D(3) ligand [(123)I]-epidepride and single photon emission tomography were used to estimate D(2)/D(3) specific binding and an index of relative percentage D(2)/D(3) occupancy in striatal and temporal cortical regions for quetiapine-treated patients (n=6). Quetiapine-, and previously studied typical-antipsychotic- and clozapine-treated patients were compared. RESULTS: Mean (s.d.) relative percentage D(2)/D(3) receptor occupancy by quetiapine was 32.0% (14.6) in striatum and 60.1% (17.2) in temporal cortex (mean daily dose 450 mg: range 300-700 mg/day). Quetiapine treatment resulted in limbic selective D(2)/D(3) blockade similar to clozapine and significantly higher than typical antipsychotics. CONCLUSIONS: Preliminary data suggest that limbic selective D(2)/D(3) receptor blockade is important for atypical drug action.

Adult↗