Being equipped for clinical PET.
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Biomedical subjects
Publications and source records attributed to M J O'Doherty.
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A strategy for the solid phase synthesis of [18F]labelled peptides has been developed. The peptides were prepared on solid support and acylated with 4-[18F]fluorobenzoic acid using HATU within 3 min and the labelled peptide was released from the solid support within 7 min. The [18F]labelled peptides were produced in good purity with a specific activity of 20-25 GBq/micromol.
Increasingly hospitals are showing an interest in developing their imaging services to include positron emission tomography (PET). There is therefore a need to be aware of the radiation doses to critical groups. To assess the effective whole-body dose received by technologists within our dedicated PET centre, each staff member was issued with a dose rate meter, and was instructed to record the time spent in contact with any radioactive source, the dose received per working day and the daily injected activity. On average each technologist administered 831 MBq per day. The mean whole-body dose per MBq injected was 0.02 microSv/MBq(-1). The average time of close contact (<2.0 m) with a radioactive source per day was 32 min. The average effective dose per minute close contact was 0.5 microSv/min(-1), which resulted in a mean daily effective dose of 14.4 microSv. No technologist received greater than 60 microSv (the current UK limit for non-classified workers) in any one day, and in general doses received were less than 24 microSv, the daily dose corresponding to the proposed new annual limit for non-classified workers of 6.0 mSv per annum. However, we recognise that the layout of nuclear medicine departments will not mirror our own. We therefore measured the instantaneous dose rates at 0.1, 0.5, 1.0 and 2.0 m from the mid-thorax on 115 patients immediately after injection, to provide estimates of the likely effective doses that might be received by technologists operating dual-headed coincidence detection systems, and others coming into contact in the waiting room with patients who have been injected with fluorine-18 fluorodeoxyglucose. The mean (95th percentile) dose rates measured at the four aforementioned distances were 391.7 (549.5), 127.0 (199.8), 45.3 (70.0) and 17.1 (30.0) microSv/h(-1), respectively. A number of situations have been modelled showing that, with correct planning, FDG studies should not significantly increase the effective doses to technologists. However, one possible area of concern is that, depending on the number of patients in a waiting area at any one time, accompanying persons may approach the limits set by the new UK IRR 1999 regulations for members of the public.
Testicular cancer is a rare tumour with the potential for cure at diagnosis. It is important, however, to identify those patients with metastases at presentation so as to ensure that the optimum treatment strategy is employed. Many criteria have been used to try to place patients into high- or low-risk groups, with variable success. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has the potential to identify active disease and thereby influence further management. Here we report on a retrospective study of the use of FDG-PET in the detection of metastatic testicular carcinoma at diagnosis. Thirty-one patients [13 with seminoma and 18 with non-seminomatous germ cell tumours (13 teratomas, 5 mixed)] were staged by FDG-PET scanning. The imaging was performed using a Siemens ECAT 951 scanner. All results were assessed on the basis of histology or clinical follow-up. FDG-PET scan identified metastatic disease in ten and was negative in 16; there were no false-positives and five false-negatives. There were six patients in whom FDG-PET was negative and computed tomography was regarded as suspicious but follow-up was inconclusive. The positive predictive value was 100%. The negative predictive value was 76% or 91%, depending on whether the aforementioned six cases were regarded as true-negatives or false-negatives. It may be concluded that FDG-PET is capable of detecting metastatic disease at diagnosis that is not identified by other imaging techniques. These preliminary results are sufficient to suggest that a large prospective study should be performed to evaluate the role of FDG-PET in primary staging of disease.
OBJECTIVE: Positron emission tomography (PET) is being increasingly used as an accurate and non-invasive modality in diagnosis, staging and post-therapy assessment in patients with lung cancer. In this study, we examine whether the uptake of [(18)F]fluorodeoxyglucose (FDG), a marker of increased glucose metabolism in neoplastic cells, is of prognostic value in patients with primary lung cancer. METHODS: We have retrospectively analyzed 77 patients (mean age, 63. 0 years; male/female ratio, 53:24) with primary lung cancers who underwent whole body and localized thoracic PET as part of their diagnostic and staging procedures prior to consideration of surgical resection. The standardized uptake value (SUV) of injected FDG for each primary lesion was correlated with tumour histology and the patient's clinical outcome. RESULTS: A SUV of 20 or greater was found to be of significant prognostic value. The chance of survival (with 95% confidence intervals (CI)) at 12 months post-surgery for the various SUV groups was as follows: 75.2% (59.6-85.5) for SUV<10; 67.5% (29.0-88.2) for SUV 10-<12; 63.6% (29.7-84.5) for SUV 12-<15; 66.7% (19.5-90.4) for SUV 15-<20; 16.7% (0.01-0.52) for SUV>20. A SUV of 20 or more is associated with a 4.66 times increase in hazard, compared with lower levels of SUV. We found no significant correlation between tumour histology and SUV. CONCLUSION: We have previously reported on the significant advantages of PET in the staging and surgical care of patients with lung cancer. The present study adds further support for an additional prognostic role for PET in the management of thoracic malignancy as determined by the amount of labelled-FDG taken up by the primary lesion.
PURPOSE: Optimum therapy for patients with Hodgkin's disease (HD) is determined by a number of prognostic factors, one of which is an accurate definition of extent of disease (stage). Computerised tomography is widely used in staging but cannot reliably evaluate normal sized lymph nodes and some extranodal sites, e.g., liver, spleen and bone marrow. 2-Fluorine-18-fluoro-2-deoxy-D glucose (FDG) has been shown to concentrate preferentially in lymphoma sites (whether in nodal or extranodal tissue) and therefore may have a useful role in staging patients with HD. This study compares concurrent computerized tomography (CT) and FDG positron emission tomography (PET) in the staging of Hodgkin's disease and assesses the frequency of stage migration and possible changes in therapy related to the use of PET scanning. PATIENTS AND METHODS: This was a single centre retrospective study of 44 patients with Hodgkin's disease who underwent both staging CT and PET prior to treatment between September 1993 and August 1998 at St. Thomas' Hospital. The number and sites of disease were assessed for each patient, documenting any stage and therapy modification prompted by PET findings. RESULTS: One hundred fifty-nine sites of disease were demonstrated in forty-four patients by FDG-PET compared with eighty-four by CT. As a result, 18 (40.9%) patients were upstaged, nine of these by FDG-uptake in splenic or extranodal sites not visualised on CT. Only three patients were downstaged by PET results. Eleven patients (25%) had treatment modified by PET scan findings. CONCLUSIONS: Significantly more sites of disease were identified by PET than CT resulting in stage changes and a modification of therapy in 25% of patients. This has important implications not only for current patient management but also for the design of future clinical trials.
Differentiation of active disease from fibrosis/mature teratoma in patients with residual masses or identifying of sites of recurrence in patients with raised markers following treatment of their testicular cancer remains a problem.(18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) has the potential to identify active disease and thereby influence further management in these patients. We performed a retrospective study of the use of FDG-PET in detecting residual/recurrent testicular carcinoma in 55 patients (seventy FDG-PET scans). Forty-seven scans were for the assessment of residual masses (18 had raised markers) and 23 scans were for the investigation of raised markers in the presence of normal CT scans. True positive results were based on positive histology or clinical follow-up. FDG-PET had a positive predictive value (PPV) of 96% and a negative predictive value (NPV) of 90% in patients with residual masses. This PPV was equivalent to that of markers (94%) but FDG-PET had the advantage of identifying the site of that recurrence. The NPV was higher than that of markers. In patients with raised markers alone the PPV of FDG-PET was 92% but the NPV was only 50%. However, subsequent FDG-PET imaging was frequently the first imaging modality to identify the site of disease. FDG-PET effected a management change in 57% of cases. FDG-PET scanning detected viable tumour in residual masses and identified sites of disease in suspected recurrence.
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OBJECTIVES: The ability of (18)fluorodeoxyglucose positron emission tomography ((18)FDG PET) to detect malignant change in plexiform neurofibromas from patients with neurofibromatosis 1 (NF1) was evaluated. METHODS: Eighteen NF1 patients who presented with pain, increase in size, or neurological deficit associated with a plexiform neurofibroma were assessed. Magnetic resonance imaging determined the site and extent of the lesion. Qualitative(18)FDG PET was performed and the standard uptake value (SUV) measured the regional glucose metabolism. Histological confirmation of the diagnosis was obtained in 10 patients. RESULTS: Twenty three plexiform neurofibromas were detected in 18 patients. Seven malignant peripheral nerve sheath tumours, four high grade and three low grade tumours, occurred in five patients. In one patient the clinical and radiological characteristics of the tumour suggested malignancy, but histology was inconclusive. Fifteen benign plexiform neurofibromas were identified in 12 patients and these findings were confirmed histologically in five lesions from four patients. Ten plexiform neurofibromas occurring in eight patients were considered benign on(18)FDG PET and the patients did not undergo surgery. They remained stable or their symptoms improved on clinical follow up (median 9 months). The results of qualitative (18)FDG PET were interpreted as indicating that 13 plexiform neurofibromas were benign and 10 were malignant. No malignant tumours were classified as benign, but two benign tumours were reported as malignant. The SUV was calculated for 20 tumours and was significantly higher in five malignant tumours 5.4 (SD 2.4), than in 15 benign tumours 1.54 (SD 0.7), p=0.002. There was an overlap between benign and malignant tumours in the SUV range 2.7-3.3. CONCLUSIONS: (18)FDG PET is helpful in determining malignant change in plexiform neurofibromas in NF1. Increased separation between benign and malignant lesions could be obtained by calculating the SUV at about 200 minutes after injection of (18)FDG, when the peak activity concentration is obtained in malignant tumours.
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Less than 50% of newly diagnosed patients with aggressive histology Non-Hodgkin's Lymphoma (NHL) are cured with standard treatment. The ability to accurately monitor response to treatment is crucial in order to select out patients who need more intensive or salvage treatment. This study assesses the accuracy of FDG-PET as compared to CT in remission assessment following treatment of aggressive NHL, and its value in estimating relapse-free survival. It also evaluates the prognostic value of early interim PET scan in prediction of treatment outcome. Forty-nine adult patients with biopsy-proven aggressive NHL between September 1993 and December 1997 were included. All patients had pre-treatment FDG-PET demonstrating increased uptake in sites of disease. Forty-five patients had a post-treatment PET to assess remission status and 4 had an interim but not a post-treatment PET. Thirty-three of these patients also had a pre- and a post-treatment CT scan. Twenty-three of the 49 patients had an interim PET during chemotherapy to assess early response. PET and CT scan results were correlated with relapse data to examine their accuracy in remission assessment and prediction of prognosis. The median follow-up duration is 30 months. Overall the result of post-treatment PET scan appears to predict disease outcome, with relapse rates of 100% (9/9) and 17% (6/36) for positive and negative PET respectively [p<0.001]. In a subgroup of 33 patients, direct comparison of post-treatment PET and CT shows that PET was more accurate than CT in assessing remission status following treatment. Relapse rate was 100% for positive PET and only 18% for negative PET (p<0.001), compared to 41% and 25% for patients with positive and negative CT respectively (p>0.1). PET was particularly useful in assessment of residual masses seen on CT scan. The interim PET provided valuable information regarding early assessment of response and long-term prognosis, with no relapses in patients with no or minimal residual uptake compared to 87.5% relapse rate in patients with persistent PET activity (p<0.001). FDG-PET is an accurate method of assessing remission and estimating prognosis following treatment of aggressive NHL, with positive and negative predictive accuracies of 100% and 82% respectively. PET is more accurate than CT in assessing remission and prediction of relapse-free survival. An interim PET scan after 2-3 cycles of chemotherapy predicts the long-term outcome early-on and has a high negative predictive value (100%). This may assist to separate at an early stage good-prognosis patients who are likely to be cured with standard chemotherapy from those patients with poorer prognosis who require alternative treatment.
BACKGROUND: The problem of residual masses on post-treatment CT scans is a continuing dilemma for the oncologist treating malignant lymphomas. These masses may contain active disease or represent only necrotic tumour which continues to shrink without further treatment or post-treatment fibrosis which remains stable on continued follow-up. 18-FDG-PET offers a novel metabolic imaging modality, which can differentiate malignant from benign tissue on the basis of increased glycolytic activity. PATIENTS AND METHODS: Thirty-two patients (15 with Hodgkin's disease (HD) and 17 with aggressive histology non-Hodgkin's lymphoma (NHL)) who had residual masses on their post-treatment CT scans underwent 18-FDG-PET. The post-treatment CT and PET scans were compared and the accuracy of the 18-FDG-PET in assessing residual masses was evaluated using clinical and pathological follow-up data. RESULTS: Nine patients had positive post-treatment 18-FDG-PET, eight (89%) of whom have relapsed. Twenty-three patients had negative post-treatment PET with only two relapses in this group. The 2 patients who relapsed had aggressive NHL while none of the 11 HD patients with negative PET relapsed. The median follow-up of patients in continued complete remission is 38 months. CONCLUSIONS: 18-FDG-PET can differentiate between residual masses containing viable lymphoma where further treatment will be required to achieve cure and those representing ablated disease, where unnecessary treatment and additional morbidity may be avoided.
We have undertaken a retrospective analysis of all positron emission tomography (PET) scans carried out at St Thomas' Hospital, London, since 1994 to establish the sensitivity and specificity of this radiologic technique in cutaneous malignant melanoma. In particular, we have identified those patients with primary cutaneous malignant melanoma in whom PET scanning revealed in-transit or regional spread to nodes and those patients with known regional spread in whom PET scanning revealed distant metastases. We defined our false-negative results as a negative scan result with positive histology or subsequent clinical progression of disease. False-positive results were defined as a suspect scan with negative histology or no subsequent progression of disease. PET scanning had an overall sensitivity of 78% and specificity of 87%; however, subset analysis (M. D. Anderson staging system) showed a sensitivity of 50% for stage I disease (34 patients and 35 scans) and 33% for stage II disease (9 patients and 9 scans) with specificities of 87% and 100%, respectively. For stage III disease (16 patients and 17 scans), PET showed a sensitivity of 93% and specificity of 50%. Overall, 35% of patients with true-positive scans had their disease restaged. We can conclude therefore that PET is valuable as a staging procedure in patients with known regional spread but is suboptimal in the prediction of outcome in stage I or stage II disease.
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Rhenium-188 dimercaptosuccinic acid complex [188Re(V)DMSA], a potential therapeutic analogue of the tumour imaging agent 99mTc(V)DMSA, is selectively taken up in bone metastases in patients with prostate cancer. It would be helpful in planning palliative radionuclide therapy if 99mTc(V)DMSA could be used to predict tumour and kidney retention of 188Re(V)DMSA. The aim of this study was to determine the correlation between tumour-to-normal tissue ratios and kidney-to-soft tissue ratios of 99mTc(V)DMSA and 188Re(V)DMSA. This would determine whether a scan with 99mTc(V) DMSA could be used to identify patients for whom 188Re(V)DMSA treatment would be contra-indicated, and enable prediction of relative kidney and tumour radiation absorbed dose in 188Re(V)DMSA treatment. Ten patients with prostate carcinoma were recruited following observation of disseminated bone metastases on a recent 99mTc-hydroxydiphosphonate bone scan. Whole-body planar scans were obtained at ca. 4 h and 24 h after hydration and injection of 600 MBq 99mTc(V)DMSA, and a week later, at similar times after hydration and injection of 370 MBq 188Re(V)DMSA. A triple-energy window (TEW) scatter correction was applied to the 188Re scans. Counts per pixel were determined in regions of interest drawn over metastatic sites, kidneys and normal soft tissue. Tumour-to-soft tissue ratios were significantly lower (by a factor of approximately 0.8 after the TEW was applied) on 188Re scans than on 99mTc scans, but the two were highly linearly correlated both in all individual patients and in tumours pooled from all patients together both at 4 h and at 24 h. Kidney-to-soft tissue ratios were similarly correlated and were lower for 188Re than for 99mTc by a similar factor. Both tumour- and kidney-to-soft tissue ratios increased between 4 and 24 h but the latter increased more. In conclusion, only minor differences were seen between 99mTc and 188Re scans, and kidney-to-background ratios on 188Re scans were not higher than on 99mTc scans. These differences are insufficient to infer that they are due to a real difference in biodistribution, and they may be due only to different physical imaging characteristics. Thus 99mTc(V)DMSA scans are predictive of 188Re(V)DMSA biodistribution and could be used to estimate tumour and renal dosimetry and assess suitability of patients for 188Re(V)DMSA treatment.
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