Are restrictions to behaviour of patients required following fluorine-18 fluorodeoxyglucose positron emission tomographic studies?

The clinical use of positron emission tomography (PET) is expanding rapidly in most European countries. It is likely therefore that patients receiving the tracer fluorine-18 fluorodeoxyglucose (¹⁸FDG) will be discharged to come into contact with family members, members of the public and ward staff. There are few direct measurements on which to base any recommendations with regard to radiation protection, and so we have measured the dose rates from patients undergoing clinical PET examinations in our centre. Seventy-five patients who underwent whole-body and brain ¹⁸FDG PET examinations were studied. Dose rates were measured at 0.1, 0.5, 1.0 and 2.0 m from the mid thorax on leaving the department. The median administered activity was 323 MBq with a 95th percentile value of 360 MBq. The median dose rates measured at the four distances were 90.0, 35.0, 14.0 and 5.0 μSv h^–1 (the median dose rates per unit administered activity at 2 h post injection were 0.31, 0.11, 0.04 and 0.02 μSv h^–1 MBq^–1). The corresponding 95th percentile values were 174.0, 69.0, 29.0 and 7.5 μSv h^–1 (0.43, 0.2, 0.08 and 0.03 μSv h^–1 MBq^–1). A number of social situations were modelled and an annual dose limit of 1 mSv was used to determine whether restrictive behavioural advice was required. In the case of nursing staff on wards a value of 6 mSv was regarded as the annual limit, which translates to a daily limit of approximately 24 μSv. There is no need for restrictive advice for patients travelling by public or private transport when they leave the department 2 h after the administration of ¹⁸FDG. Similarly, there is no need for restrictive advice with regard to their contact with partners, work colleagues or children of any age, although it should be stressed that children should not accompany the patient to the scanning department. The only possible area of concern is in an oncology ward, where patients may be regularly referred for PET investigations and other high activity radionuclide studies and are partially helpless. Even in this area, however, it is unlikely that a nurse would receive a daily dose of more than 24 μSv. We conclude that there is no need for restrictive advice for patients undergoing ¹⁸FDG PET studies given the current administered activities. Received 27 July and in revised form 25 September 1998     

Radiation dose rates from patients undergoing positron emission tomography: implications for technologists and waiting areas

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 μSv/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 μSv/min^–1, which resulted in a mean daily effective dose of 14.4 μSv. No technologist received greater than 60 μSv (the current UK limit for non-classified workers) in any one day, and in general doses received were less than 24 μSv, 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 detectionsystems, 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) μSv/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. Received 30 September and in revised form 27 December 1999     

Dual-head gamma camera 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography in oncological patients: effects of non-uniform attenuation correction on lesion detection

The purpose of this study was to evaluate a dual head coincidence gamma camera (DH-PET) equipped with single-photon transmission for 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) imaging in oncological patients. Forty-five patients with known or suspected malignancies, scheduled for a positron emission tomography (PET) scan, were first studied with a dedicated ring PET and subsequently with DH-PET. All patients underwent measured attenuation correction using germanium-68 rod sources for ring PET and caesium-137 sources for DH-PET. Ring PET emission scan was started 64±17 min after intravenous administration of 235±42 MBq FDG. DH-PET emission followed 160±32 min after i.v. FDG. Attenuation-corrected and non-attenuation-corrected images were reconstructed for ring PET and DH-PET. The image sets were evaluated independently by three observers blinded to clinical data and to results of conventional imaging. Attenuation-corrected ring PET as the standard of reference depicted 118 lesions, non-attenuation-corrected ring PET 113 (96%) lesions, and attenuation-corrected DH-PET and non-attenuation-corrected DH-PET, 101 (86%) and 84 (71%) lesions, respectively (P<0.05). The lesion detection rate of attenuation-corrected and non-attenuation-corrected DH-PET was almost similar for lesions >20 mm, whereas attenuation correction increased the detection rate from 60% to 80% for lesions ≤20 mm (P<0.01). A patient-based analysis revealed concordant results relative to attenuation-corrected ring PET for non-attenuation-corrected ring PET, attenuation-corrected DH-PET and non-attenuation-corrected DH-PET in 42 (93%), 36 (80%) and 31 (69%) patients, respectively. Differences might have influenced patient management in two (4%), six (13%) and ten (22%) patients, respectively. In conclusion, measured attenuation correction markedly improves the lesion detection capability of DH-PET. With measured attenuation correction the diagnostic performance of DH-PET is closer to that of dedicated ring PET. Received 9 April and in revised form 20 April 1999     

Estimation of absorbed dose for 2-[F-18]fluoro-2-deoxy-d- glucose using whole-body positron emission tomography and magnetic resonance imaging

The purpose of this study was to measure the cumulated activity and absorbed dose in organs after intravenous administration of 2-[F-18]fluoro-2-deoxy-d-glucose (¹⁸F-FDG) using whole-body positron emission tomography (PET) and magnetic resonance imaging (MRI). Whole-body dynamic emission scans for ¹⁸F-FDG were performed in six normal volunteers after transmission scans. The total activity of a source organ was obtained from the activity concentration of the organ measured by whole-body PET and the volume of that organ measured by whole-body T1-weighted MRI. The cumulated activity of each source organ was calculated from the time-activity curve. Absorbed doses to the individuals were estimated by the MIRD (medical internal radiation dosimetry) method using S-values adjusted to the individuals. Another calculation of cumulated activities and absorbed doses was performed using the organ volumes from the MIRD phantom and the ”Japanese reference man” to investigate the discrepancy of actual individual results against the phantom results. The cumulated activities of 18 source organs were calculated, and absorbed doses of 27 target organs estimated. Among the target organs, bladder wall, brain and kidney received the highest doses for the above three sets of organ volumes. Using measured individual organ volumes, the average absorbed doses for those organs were found to be 3.1×10^–1, 3.7×10^–2 and 2.8×10^–2 mGy/MBq, respectively. The mean effective doses in this study for individuals of average body weight (64.5 kg) and the MIRD phantom of 70 kg were the same, i.e. 2.9×10^–2 mSv/MBq, while for the Japanese reference man of 60 kg the effective dose was 2.1×10^–2 mSv/MBq. The results for measured organ volumes derived from MRI were comparable to those obtained for organ volumes from the MIRD phantom. Although this study considered ¹⁸F-FDG, combined use of whole-body PET and MRI might be quite effective for improving the accuracy of estimations of the cumulated activity and absorbed dose of positron-labelled radiopharmaceuticals. Received 23 October 1997 and in revised form 31 January 1998     

Positron emission tomographic assessment of ”metabolic flare” to predict response of metastatic breast cancer to antiestrogen therapy

We have investigated whether increased tumor uptake of fluorine-18 fluorodeoxyglucose (FDG) detected with positron emission tomography (PET) early after initiating tamoxifen therapy (”metabolic flare”) predicts a hormonally responsive breast cancer. Eleven postmenopausal women with biopsy-proved estrogen receptor-positive (ER+) metastatic breast cancer were studied by PET with FDG and 16α[¹⁸F]fluoro-17β-estradiol (FES) before and 7–10 days after initiation of tamoxifen therapy. FDG and FES uptake was evaluated semiquantitatively in 21 lesions. The PET results were correlated with follow-up evaluation, continued until the patient became unresponsive to hormone therapy (3–24 months). There were seven responders and four nonresponders based on clinical follow-up. None of the responders had a clinical flare reaction, but all demonstrated metabolic flare, with a mean ± standard deviation increase in tumor standardized uptake value (SUV) for FDG of 1.4±0.7. No evidence for flare was noted in the nonresponders (change in SUV for FDG –0.1±0.4; P = 0.008 vs. responders). The degree of ER blockade by tamoxifen was greater in responders (mean decrease in SUV 2.7±1.7) than in nonresponders (mean decrease 0.8±0.5) (P = 0.04). The lesions of responders had higher baseline SUVs for FES than did those of three of four nonresponders (≥2.2 vs ≤1.7). The findings of a metabolic flare by FDG-PET and the degree of ER blockade by FES-PET early after institution of tamoxifen treatment appear to predict responsiveness to antiestrogen therapy in patients with ER+ metastatic breast cancer. Received 13 August and in revised form 6 September 1998     

Dosimetry of transmission measurements in nuclear medicine: a study using anthropomorphic phantoms and thermoluminescent dosimeters

Quantification in positron emission tomography (PET) and single photon emission tomographic (SPET) relies on attenuation correction which is generally obtained with an additional transmission measurement. Therefore, the evaluation of the radiation doses received by patients needs to include the contribution of transmission procedures in SPET (SPET-TM) and PET (PET-TM). In this work we have measured these doses for both PET-TM and SPET-TM. PET-TM was performed on an ECAT EXACT HR+ (CTI/Siemens) equipped with three rod sources of germanium-68 (380 MBq total) and extended septa. SPET-TM was performed on a DST (SMV) equipped with two collimated line sources of gadolinium-153 (4 GBq total). Two anthropomorphic phantoms representing a human head and a human torso, were used to estimate the doses absorbed in typical cardiac and brain transmission studies. Measurements were made with thermoluminescent dosimeters (TLDs, consisting of lithium fluoride) having characteristics suitable for dosimetry investigations in nuclear medicine. Sets of TLDs were placed inside small plastic bags and then attached to different organs of the phantoms (at least two TLDs were assigned to a given organ). Before and after irradiation the TLDs were placed in a 2.5-cm-thick lead container to prevent exposure from occasional sources. Ambient radiation was monitored and taken into account in calculations. Transmission scans were performed for more than 12 h in each case to decrease statistical noise fluctuations. The doses absorbed by each organ were calculated by averaging the values obtained for each corresponding TLD. These values were used to evaluate the effective dose (ED) following guidelines described in ICRP report number 60. The estimated ED values for cardiac acquisitions were 7.7×10^–4±0.4×10^–4 mSv/MBq · h and 1.9×10^–6±0.4×10^–6 ███/MBq · h for PET-TM and SPET-TM. respectively. For brain scans, the values of ED were calculated as 2.7×10^–4±0.2×10^–4 mSv/MBq · h for PET-TM and 5.2×10^–7±2.3×10^–7 mSv/MBq · h for SPET-TM. In our institution, PET-TM is usually performed for 15 min prior to emission. SPET-TM is performed simultaneously with emission and usually lasts 30 and 15 min for brain and cardiac acquisitions respectively. Under these conditions ED values, estimated for typical source activities at delivery time (22000 MBq in SPET and 555 MBq for PET), were 1.1×10^–1± 0.1×10^–1 mSv and 1.1×10^–2±0.2×10^–2 mSv for cardiac PET-TM and SPET-TM respectively. For brain acquisitions, the ED values obtained under the same conditions were 3.7×10^–2±0.3×10^–2 mSv and 5.8×10^–3±2.6×10^–3███ for PET-TM and SPET-TM respectively. These measurements show that the dose received by a patient during a transmission scan adds little to the typical dose received in a routine nuclear medicine procedure. Radiation dose, therefore, does not represent a limit to the generalised use of transmission measurements in clinical SPET or PET. Received 12 May and in revised form 1 July 1998     

Biodistribution and radiation dosimetry in healthy volunteers of a novel tumour-specific probe for PET/CT imaging: BAY 85-8050

Purpose

Novel tracers for the diagnosis of malignant disease with PET and PET/CT are being developed as the most commonly used ¹⁸F deoxyglucose (FDG) tracer shows certain limitations. Employing radioactively labelled glutamate derivatives for specific imaging of the truncated citrate cycle potentially allows more specific tumour imaging. Radiation dosimetry of the novel tracer BAY 85-8050, a glutamate derivative, was calculated and the effective dose (ED) was compared with that of FDG.

Methods

Five healthy volunteers were included in the study. Attenuation-corrected whole-body PET/CT scans were performed from 0 to 90 min, at 120 and at 240 min after injection of 305.0?±?17.6 MBq of BAY 85-8050. Organs with moderate to high uptake at any of the imaging time points were used as source organs. Total activity in each organ at each time point was measured. Time–activity curves (TAC) were determined for the whole body and all source organs. The resulting TACs were fitted to exponential equations and accumulated activities were determined. OLINDA/EXM software was used to calculate individual organ doses and the whole-body ED from the acquired data.

Results

Uptake of the tracer was highest in the kidneys due to renal excretion of the tracer, followed by the pancreas, heart wall and osteogenic cells. The mean organ doses were: kidneys 38.4?±?11.2 μSv/MBq, pancreas 23.2?±?3.8 μSv/MBq, heart wall 17.4?±?4.1 μSv/MBq, and osteogenic cells 13.6?±?3.5 μSv/MBq. The calculated ED was 8.9?±?1.5 μSv/MBq.

Conclusion

Based on the distribution and dose estimates, the calculated radiation dose of BAY 85-8050 is 2.67?±?0.45 mSv at a patient dose of 300 MBq, which compares favourably with the radiation dose of FDG (5.7 mSv).     

Radiation doses deriving from patients undergoing 111In-DTPA-d-Phe-1-octreotide scintigraphy

The purpose of this study was to estimate the radiation doses to nursing staff, other patients, accompanying persons and family members deriving from patients undergoing ¹¹¹In-DTPA-d-Phe-1-octreotide (¹¹¹In-OCT) scintigraphy. Dose rates were measured from 16 patients who had received an intravenous injection of 140±40 MBq ¹¹¹In-OCT. The measurements were performed at three different distances (0.5, 1 and 2 m) at 10–20 min, 5–7 h and 24 h (and in some cases, up to 48 h) after administration of ¹¹¹In-OCT. The effective half-lives of the biexponential decrease of the dose rates were estimated to be 2.94±0.27 h (T ₁) and 65.17±0.58 h (T ₂). The calculated maximum dose to other persons in the waiting area was 27.2 μSv, to family members 61.5 μSv, to nursing staff in a ward 24.1 μSv and to neighbouring patients in the ward 69.5 μSv. Our results clearly demonstrate that the calculated maximum radiation exposure to accompanying persons, personnel, family members and other patients is well below the maximum annual dose limit for non-professionally exposed persons. Received 20 May and in revised form 9 July 1997     

Mediastinal staging of lung cancer with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography and a dual-head coincidence gamma camera

The aims of the present study were (a) to evaluate mediastinal staging in patients with lung cancer with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) using a coincidence gamma camera (hybrid PET) in comparison with dedicated positron emission tomography (PET) and computed tomography (CT), and (b) to assess the feasibility to determine standardized uptake values (SUV) with hybrid PET. Forty patients were included in the study. Hybrid PET was performed without and with attenuation correction. Data were rebinned with single-slice (SSRB) or Fourier rebinning (FORE). The SUVs of primary tumors were calculated with hybrid PET and compared with SUVs determined by dedicated PET. Diagnostic accuracy for hybrid with or without attenuation correction was 80 or 74% compared with 82% for dedicated PET, and 63% for CT. Attenuation-corrected hybrid PET revealed a higher specificity than CT (83 vs 52%; p<0.05). The SUVs of primary tumors were similar to those of hybrid PET and dedicated PET with a mean relative difference of 20.8±16.4%. The FORE improved the agreement of SUVs with a mean relative difference of 13.8±9.9 vs 36.0±17.9% for SSRB (p<0.001). Hybrid PET with attenuation correction is more specific than CT for mediastinal staging in patients with lung cancer (p<0.05). It reveals similar results in comparison with dedicated PET. Calculation of SUVs with hybrid PET is feasible. Electronic Publication     

Human biodistribution and dosimetry of 18F-JNJ42259152, a radioligand for phosphodiesterase 10A imaging

Purpose

Phosphodiesterase 10A (PDE10A) is a cAMP/cGMP-hydrolysing enzyme with a central role in striatal signalling and implicated in neuropsychiatric disorders such as Huntington’s disease, Parkinson’s disease, schizophrenia and addiction. We have developed a novel PDE10A PET ligand, ¹⁸F-JNJ42259152, and describe here its human dynamic biodistribution, safety and dosimetry.

Methods

Six male subjects (age range 23–67 years) underwent ten dynamic whole-body PET/CT scans over 6 h after bolus injection of 175.5?±?9.4 MBq ¹⁸F-JNJ42259152. Source organs were delineated on PET/CT and individual organ doses and effective dose were determined using the OLINDA software.

Results

F-JNJ42259152 was readily taken up by the brain and showed exclusive retention in the brain, especially in the striatum with good washout starting after 20 min. The tracer was cleared through both the hepatobiliary and the urinary routes. No defluorination was observed. Organ absorbed doses were largest for the gallbladder (239 μSv/MBq) and upper large intestine (138 μSv/MBq). The mean effective dose was 24.9?±?4.1 μSv/MBq. No adverse events were encountered.

Conclusion

In humans, ¹⁸F-JNJ42259152 has an appropriate distribution, brain kinetics and safety. The estimated effective dose was within WHO class IIb with low interindividual variability. Therefore, the tracer is suitable for further kinetic evaluation in humans.     

Imaging of lung cancer with fluorine-18 fluorodeoxyglucose: comparison of a dual-head gamma camera in coincidence mode with a full-ring positron emission tomography system

Dual-head gamma cameras operated in coincidence mode are a new approach for tumour imaging using fluorine-18 fluorodeoxyglucose (FDG). The aim of this study was to assess the diagnostic accuracy of such a camera system in comparison with a full-ring positron emission tomography (PET) system in patients with lung cancer. Twenty-seven patients (1 female, 26 males, age 62±9 years) with lung cancer or indeterminate pulmonary nodules were studied on the same day with a full-ring PET scanner (Siemens ECAT EXACT) and a coincidence gamma camera system (ADAC Vertex MCD). Sixty minutes after injection of 185–370 MBq FDG, a scan of the chest was performed with the full-ring system. Approximately 2 h p.i., the coincidence camera study was performed. Coincidence gamma camera (CGC) and PET images with (PETac) and without attenuation correction (PETnac) were analysed independently by two blinded observers. In addition, FDG uptake in primary tumours and involved lymph nodes was quantified relative to normal contralateral lung (T/L ratios). All primary tumours were histologically proven. The lymph node status was histologically determined in 23 patients. In four patients, no lymph node sampling was performed because of extensive disease or concurrent illnesses. In the 27 patients, 25 primary lung cancers and two metastatic lesions were histologically diagnosed. The number of coincidences per centimetre axial field of view was 3.33±0.93×10⁵ for the CGC and 1.09±0.36×10⁶ for the dedicated PET system. All primary tumours (size: 4.6±2.6 cm) were correctly identified in the CGC and dedicated PET studies. T/L ratios were 4.7±2.5 for CGC and 6.9±2.8 for PETnac (P <0.001). Histopathological evaluation revealed lymph node metastases in 11 of 88 sampled lymph node stations (size: 2.3±1.0 cm). All lymph node metastases were identified in the PETac studies, while PETnac detected 10/11 and CGC 8/11. For positive lymph nodes that were visible in CGC and PETnac studies, T/L ratios were 3.7±2.3 for CGC and 6.6±3.1 for PETnac (P=0.02). The diameters of false-negative lymph nodes in the CGC studies were 0.75, 1.5 and 2 cm. False-positive FDG uptake in lymph nodes was found in two patients with all three imaging methods. For all lesions combined, T/L ratios in CGC relative to PETnac studies decreased significantly with decreasing lesion size (r=0.62; P<0.001). In conclusion, compared with a full-ring PET system the sensitivity of CGC imaging for detection of lung cancer is limited by a lower image contrast which deteriorates with decreasing lesion size. Nevertheless, the ability of CGC imaging to detect pulmonary lesions with a diameter of at least 2 cm appears to be similar to that of a full-ring system. Both systems provide a similar specificity for the evaluation of lymph node involvement. Received 29 August and in revised form 7 December 1998     

Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent — a pilot study

PurposeThe compound (E)-4-(2-(6-(2-(2-(2-¹⁸F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)-N-methylbenzenamine ([¹⁸F]AV-45) is a novel radiopharmaceutical capable of selectively binding to β-amyloid (Aβ) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [¹⁸F]AV-45 in human subjects.MethodsIn vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer's disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0±5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9±13.9 MBq of [¹⁸F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7±13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information.ResultsIn vitro autoradiography revealed exquisitely high specific binding of [¹⁸F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12±0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7±78.6 μGy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [¹⁸F]AV-45 were 33.8±3.4 μSv/MBq and 19.3±1.3 μSv/MBq, respectively.Conclusion[¹⁸F]AV-45 binds specifically to Aβ in vitro, and is a safe PET tracer for studying Aβ distribution in human brain. The dosimetry is suitable for clinical and research application.     

Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart

Purpose We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic β-adrenergic stimulation has been implicated in insulin resistance in cultured cardiomyocytes in vitro, where sustained noradrenaline stimulation inhibited insulin-modulated glucose uptake. As the failing heart is characterized by increased sympathetic drive, we hypothesized that there is a correlation between pre-synaptic sympathetic function and insulin sensitivity in the myocardium of patients with HF. Methods Eight patients (aged 67 ± 7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 44 ± 10%) underwent function and viability assessment with cardiovascular magnetic resonance. Myocardial glucose utilization (MGU) was measured using positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [¹¹C]meta-hydroxy-ephedrine (HED) volume of distribution (V _d) with PET. Two groups of healthy volunteers served as controls for the FDG (n = 8, aged 52 ± 4 years, p < 0.01 vs patients) and HED (n = 8, aged 40 ± 6 years, p < 0.01 vs patients) data. Results MGU in patients was reduced in both normal remote (0.44 ± 0.14 μmol·min⁻¹·g⁻¹) and dysfunctional (0.49 ± 0.14 μmol·min⁻¹·g⁻¹) segments compared with controls (0.61 ± 0.7 μmol·min⁻¹·g⁻¹; p < 0.001 vs both). HED V _d was reduced in dysfunctional segments of patients (38.9 ± 21.2 ml·g⁻¹) compared with normal segments (52.2 ± 19.6 ml·g⁻¹) and compared with controls (62.7 ± 11.3 ml·g⁻¹). In patients, regional MGU was correlated with HED V _d. Conclusion The results of this study provide novel evidence of a correlation between cardiac sympathetic function and insulin sensitivity, which may represent one of the mechanisms contributing to insulin resistance in failing human hearts.     

BMS-747 158-02: A novel PET myocardial perfusion imaging agent

Background BMS-747158-02 is a fluorine 18-labeled pyridaben derivative designed as a new myocardial perfusion imaging agent for use with positron emission tomography (PET). This study evaluated BMS-747158-02 in animal models of cardiac perfusion and compared it with established single photon emission computed tomography agents. Methods and Results In a rat biodistribution study, BMS-747158-02 (15 μCi) had substantially higher myocardial uptake than technetium 99m, sestamibi (100 μCi) at 15 minutes (3.5%±0.3% % ID/g vs 1.9%±0.1% %ID/g) and 120 minutes (3.2%±0.4% of injected dose per gram vs 1.8%±0.0% of injected dose per gram) after intravenous administration. Uptake ratios of heart to lung and liver at 60 minutes were also higher for BMS-747158-02 (12.7±1.4 and 3.7±0.2, respectively) than Tc-99m sestamibi (5.9±0.5 and 2.4±0.4, respectively). In an isolated rabbit heart model at flow rates of 1.66 to 5.06 mL · min⁻¹ · g⁻¹ wet left ventricular weight, the net BMS-747158-02 heart uptake increased proportionally (0.93±0.15 to 2.44±0.40 mL · min⁻¹ · g⁻¹) and to a greater extent than that of thallium 201 (0.76±0.02 to 1.11 ±0.02 mL · min⁻¹ · g⁻¹) or Tc-99m sestamibi (0.49±0.03 to 0.77±0.08 mL · min⁻¹ · g⁻¹). PET imaging with BMS-747158-02 showed a clear and sustained cardiac uptake in rats, rabbits, and nonhuman primates with minimal lung interference and rapid liver clearance. Myocardial perfusion deficit zones created by either permanent left coronary ligation or reperfusion after ligation in rats were both clearly identified on PET cardiac images of BMS-747158-02 and had good agreement with in vitro histology. Conclusions BMS-747158-02 exhibited high and sustained cardiac uptake that was proportional to blood flow, and it represents a new class of PET myocardial perfusion imaging agent.     

Preliminary safety evaluation of a cyclotron facility for positron emission tomography imaging

This work describes the design characteristics of a medical imaging centre which uses positron emission tomography, with a cyclotron for fluorine-18 and nitrogen-13 production, and which has provided experimental information on operational data recorded by area dosimetry since 1995. Doses to radiopharmacy and medical staff have been measured both in normal work and in some handling incidents. Data on radiation levels in the installation have also been obtained and related to design details and shielding. Area dosimetry was carried out using a five-stationary detector network, with a sampling rate of 2 min^–1, and by thermoluminescent dosimetry (TLD). Staff were also monitored by TLD, using extra chips for finger dosimetry and to duplicate individual whole-body dosimetry in order to measure doses in certain single operations. For normal work, average whole-body doses to radiopharmacy staff were between 0.03 and 0.28 mSv/month, wrist doses were between 0.42 and 2.67 mSv/month, and finger doses were between 1.4 and 7.7 mSv/day for the left hand and 0.8 and 2.4 mSv/day for the right hand; such variation reflects the differing expertise of staff and the role played by optimisation. Finger doses between 16 and 131 mSv were measured in handling incidents, and finger doses of 20.2 and 20.7 mSv for the left hand and 22.0 and 22.3 mSv for the right hand were measured during handling of a syringe without shielding, containing 3 GBq. For medical staff, contributions to the whole-body dose of 2.0 and 1.9 μSv/procedure were measured for injection and placing the patient on the examination couch, respectively. Dose measurement on the middle finger of the right hand gives an average of 70 μSv during the injection. The provisions regarding the shielding design have proved to be adequate and effective during a 3-year operational period. Operational doses to medical staff are comparatively low, while radiopharmacy staff are the most exposed. The finger doses in these professionals may exceed the annual limit, unless operational restrictions in daily practice are adopted. On-line area dosimetry records based on dose rate probes have proved to be effective both for monitoring radiation levels during the operation and for detecting changes in the behaviour of the facility in the irradiation process. Received 23 January and in revised form 12 April 1999     

Cardiac fluorine-18 fluorodeoxyglucose imaging using a dual-head gamma camera with coincidence detection: a clinical pilot study

Dual-headed gamma cameras with coincidence detection (MCD) are increasingly used for imaging of positron-emitting tracers, such as fluorine-18 fluorodeoxyglucose (FDG). In this study, we examined differences between FDG MCD and FDG positron emission tomography (PET) as the gold standard to determine whether FDG MCD could be used for assessment of myocardial viability in daily practice. Nineteen patients with a previous myocardial infarction (17 men; mean left ventricular ejection fraction 44%±13%) underwent FDG MCD, FDG PET, resting echocardiography and technetium-99m tetrofosmin gated single-photon emission tomography (SPET). At the 50% threshold value for FDG PET, the area under the receiver operating characteristic curve for FDG MCD was 0.77±0.03. In 107 dyssynergic segments on echocardiography and 151 segments with hypoperfusion on ^99mTc-tetrofosmin SPET, the specificity of FDG MCD for the detection of myocardial viability was 72% and 76% respectively, with a sensitivity of 69% and 72% respectively. Regional analysis showed a significantly lower agreement of FDG MCD and FDG PET in the inferior and septal regions (58% for dyssynergic segments and 65% for segments with hypoperfusion), as compared with the other regions (85% for dyssynergic regions, P<0.05, and 86% for segments with hypoperfusion, P<0.05). Five patients (26%), who all had a body mass index ≥25% kg/m², showed more than 25% disagreement between FDG MCD and FDG PET. Because of the moderate overall agreement with FDG PET, the low sensitivity in akinetic or dyskinetic regions and the low agreement in the inferior and septal regions, further studies and implementations of technical developments are needed before FDG MCD can be introduced into clinical practice for the assessment of myocardial viability. Received 4 December 1999 and in revised form 5 February 2000     

Basal and hyperaemic myocardial blood flow in regionally denervated canine hearts: an in vivo study with positron emission tomography

Purpose Positron emission tomography (PET) studies in patients with diabetic autonomic neuropathy (DAN) have demonstrated the impact of this disease on cardiac sympathetic innervation and myocardial blood flow (MBF). To investigate the effects of selective partial sympathetic denervation of the left ventricle (LV) on baseline and hyperaemic MBF, we measured myocardial presynaptic catecholamine re-uptake (uptake-1), β-adrenoceptor (β-AR) density and MBF non-invasively by means of PET in a canine model of regional sympathetic denervation. Methods In 11 anaesthetised dogs, the sympathetic nerves of the free wall and septum of the LV were removed by means of dissection and phenol painting. Three weeks later, the animals were studied with PET. MBF was measured at baseline and following i.v. adenosine (140 μg kg⁻¹ min⁻¹) and dobutamine (20 μg kg⁻¹ min⁻¹) using¹⁵O-labelled water. Sympathetic denervation was confirmed by an 80±12% decrease in the volume of distribution (V_d) of [¹¹C]hydroxyephedrine (HED) compared with innervated regions. Myocardial β-AR density was measured using [¹¹C]CGP12177. Results Innervated and denervated regions showed no differences in MBF at baseline and during adenosine or dobutamine. [¹¹C]HED V_dwas inversely correlated with MBF in both regions at baseline, and the correlation was lost during hyperaemia in denervated regions. However, for any given value of MBF, [¹¹C]HED V_dwas significantly lower in the denervated regions. β-AR density was comparable in denervated and innervated regions (17.9±4.2 vs 18.4±3.3 pmol g⁻¹;p=NS). Conclusion In this experimental model, selective, regional sympathetic denervation of the LV, which results in a profound reduction in [¹¹C]HED V_d, did not affect baseline or hyperaemic MBF. In addition, we demonstrated that, under baseline conditions, there was a significant inverse correlation between [¹¹C]HED V_dand MBF in both denervated and innervated regions.     

Comprehensive evaluation of occupational radiation exposure to intraoperative and perioperative personnel from <Superscript>18</Superscript>F-FDG radioguided surgical procedures

Purpose  The purpose of the current study was to comprehensively evaluate occupational radiation exposure to all intraoperative and perioperative personnel involved in radioguided surgical procedures utilizing ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG). Methods  Radiation exposure to surgeon, anesthetist, scrub technologist, circulating nurse, preoperative nurse, and postoperative nurse, using aluminum oxide dosimeters read by optically stimulated luminescence technology, was evaluated during ten actual radioguided surgical procedures involving administration of ¹⁸F-FDG. Results  Mean patient dosage of ¹⁸F-FDG was 699 ± 181 MBq (range 451–984). Mean time from ¹⁸F-FDG injection to initial exposure of personnel to the patient was shortest for the preoperative nurse (75 ± 63 min, range 0–182) followed by the circulating nurse, anesthetist, scrub technologist, surgeon, and postoperative nurse. Mean total time of exposure of the personnel to the patient was longest for the anesthetist (250 ± 128 min, range 69–492) followed by the circulating nurse, scrub technologist, surgeon, postoperative nurse, and preoperative nurse. Largest deep dose equivalent per case was received by the surgeon (164 ± 135 μSv, range 10–580) followed by the anesthetist, scrub technologist, postoperative nurse, circulating nurse, and preoperative nurse. Largest deep dose equivalent per hour of exposure was received by the preoperative nurse (83 ± 134 μSv/h, range 0–400) followed by the surgeon, anesthetist, postoperative nurse, scrub technologist, and circulating nurse. Conclusion  On a per case basis, occupational radiation exposure to intraoperative and perioperative personnel involved in ¹⁸F-FDG radioguided surgical procedures is relatively small. Development of guidelines for monitoring occupational radiation exposure in ¹⁸F-FDG cases will provide reassurance and afford a safe work environment for such personnel.     

Role of positron emission tomography using fluorine-18 fluoro-2-deoxyglucose in predicting improvement in left ventricular function in patients with idiopathic dilated cardiomyopathy

Improvement in left ventricular (LV) function in patients with idiopathic dilated cardiomyopathy (DCM) by medical treatment has been suggested. Thus, it is important to evaluate which patients will respond to medical therapy. Positron emission tomography (PET) with fluorine-18 fluoro-2-deoxyglucose (FDG) and cardiac catheterization were performed in 20 patients with DCM before the initiation of medical therapy. The regional myocardial glucose utilization rate (rMGU) was measured with FDG PET. Subjects were divided into two groups, group 1 (event-free patients, n=10) and group 2 (clinical cardiac events, n=10). Haemodynamic and PET parameters before the initiation of medication were compared between the two groups and between patients with and patients without improvement in LV function. Ejection fraction (EF) was significantly higher in group 1 (35.8%±9.0%) than in group 2 (24.8%±7.0%) and LV end-diastolic pressure (LVEDP) was significantly lower in group 1 (8.4±1.7 mmHg) than in group 2 (11.6±3.5 mmHg). Average rMGU (mg min^–1 100 g^–1) was similar in group 1 (11.2±2.5 mg min^–1 100 g^–1) and group 2 (11.2±2.9 mg min^–1 100 g^–1), while %CV of rMGU was significantly lower in group 1 (11.1%±6.3%) than in group 2 (29.9%±13.9%, P<0.01). Furthermore, LV function normalized in seven patients in group 1. In these seven patients, EF (35.1%±10.9%), LVEDP (8.2±2.0 mmHg) and average rMGU (11.8±2.7 mg min^–1 100 g^–1) were comparable with those in patients without LV functional improvement (EF: 31.6%±9.1%; LVEDP: 10.7±3.3 mmHg; average rMGU: 10.8± 2.7 mg min^–1 100 g^–1). However,% CV of rMGU in patients with LV functional improvement (9.6%±5.6%) was significantly lower than in those without such improvement (26.3%±14.1%, P<0.01). %CV of rMGU <13.6% predicted prognosis with a sensitivity of 80%, a specificity of 100% and an accuracy of 90%. %CV of rMGU <13.6% also predicted improvement in LV function, with a sensitivity of 75%, a specificity of 92% and an accuracy of 85%. However, EF failed to predict improvement of LV function. In is concluded that homogeneous myocardial glucose utilization rate can predict both prognosis and improvement in LV function achieved by medical therapy in patients with DCM. Received 9 December 1997 and in revised form 11 March 1998     

Positron detection for the intraoperative localisation of cancer deposits

Purpose The study investigated the feasibility of a positron-sensitive hand-held detector system for the intraoperative localisation of tumour deposits resulting from intravenous [¹⁸F]FDG administration. Methods A total of 17 patients (12 receiving preoperative [¹⁸F]FDG PET imaging) with various histologically proven malignancies were included. Radioactivity from tumours and surrounding normal tissue was measured on average 3 h after administration of 36–110 MBq [¹⁸F]FDG and the tumour-to-background (T/B) ratio was calculated. In addition, phantom studies were performed to evaluate the spatial resolution and sensitivity of the probe. Results All known targeted tumour sites were identified by the positron probe. T/B ratios were generally high, with a mean T/B ratio of 6.6, allowing easy identification of most tumour sites. In one case of a hepatic metastasis, the T/B ratio of 1.34 was below expectations, since the preoperative [¹⁸F]FDG PET scan was positive. The probe was instrumental in the localisation of three additional tumour lesions (two lymph nodes, one anastomotic ring) that were not immediately apparent at surgery. Phantom studies revealed that [¹⁸F]FDG-containing gel (simulating tumour tissue), having 10 times more [¹⁸F]FDG than surrounding “normal” background gel, was clearly detectable in quantities as low as 15 mg. As measured in two cases, the absorbed radiation doses ranged from 2.5 to 8.6 μSv/h for the surgical team to 0.8 μSv/h for the aesthetician. Conclusion [¹⁸F]FDG-accumulating tumour tissues can be localised with positron probes intraoperatively with a low radiation burden to the patient and medical personnel. The methodology holds promise for further clinical testing.