Perioperative PET/CT lymphoscintigraphy and fluorescent real-time imaging for sentinel lymph node mapping in early staged colon cancer.

PURPOSE: Using current optical imaging techniques and gamma imaging modalities, perioperative sentinel lymph node (SLN) identification in colon cancer can be difficult when the SLN is located near the primary tumour or beneath a thick layer of (fat) tissue. Sentinel lymph node mapping using PET/CT lymphoscintigraphy combined with real-time visualization of the SLN using near-infrared imaging has shown promising results in several types of cancer and may facilitate the successful identification of the number and location of the SLN in early colon cancer. METHODS: Clinical feasibility of PET/CT lymphoscintigraphy using preoperative endoscopically injected [89Zr]Zr-Nanocoll and intraoperative injection of the near-infrared (NIR) tracer Indocyanine Green (ICG) was evaluated in ten early colon cancer patients. Three preoperative PET/CT scans and an additional ex vivo scan of the specimen were performed after submucosal injection of [89Zr]Zr-Nanocoll. All SLNs and other lymph nodes underwent extensive pathological examination for metastases. A histopathological proven lymph node visible at preoperative PET/CT and identified at PET/CT of the specimen was defined as SLN. RESULTS: A total of 27 SLNs were harvested in seven out of eight patients with successful injection of both tracers. In one patient no SLNs were assigned preoperatively. In two patients injection of [89Zr]Zr-Nanocoll failed due to incorrect needle positioning. Twenty-one (78%) SLNs were found intraoperatively using NIR-imaging. Eleven of the 27 (41%) SLNs were located near the primary tumour (< 2 cm). Those six SLNs not found intraoperatively with NIR-imaging were all located close to the tumour. In all seven patients at least one SLN could be assigned at preoperative imaging 24 h after tracer administration. One SLN contained metastases detected by immunohistochemistry. No metastases were found in the non-SLNs. CONCLUSIONS: This study shows the potential of preoperative PET/CT lymphoscintigraphy to inform the surgeon about the number and location of SLNs in patients with early colon cancer. The additional use of NIR-imaging allows for intraoperative identification of these SLNs which are invisible with conventional white light imaging. Further research is necessary to improve and simplify the technique. We recommend perioperative SLN identification using a preoperative lymphoscintigraphy scan just before surgery approximately 24 h after injection. Additionally a postoperative scan of the specimen combined with intraoperative real-time NIR-imaging should be performed.

Pharmaceutical preparation of oxygen-15 labelled molecular oxygen and carbon monoxide gasses in a hospital setting.

BACKGROUND: Clinical positron emission tomography (PET) requires safe and effective PET radiopharmaceuticals. Tracers used for measuring oxygen consumption and blood volume are [(15)O]O(2) and [(15)O]CO, respectively. In general, these oxygen-15 labelled tracers are produced using a cyclotron that accelerates deuterons onto a target filled with (14)N(2) containing a trace of oxygen. In recent years, cyclotrons have been developed that only are capable of accelerating protons. The purpose of this study was to validate and assess such a cyclotron for production and administration of oxygen-15 labelled gasses in an hospital setting. METHODS: An RDS111 cyclotron (Siemens-CTI, Knoxville, USA) was validated for bolus production of [(15)O]O(2) and [(15)O]CO gasses. In addition, equipment was developed to administer these tracers to patients. RESULTS: Both [(15)O]O(2) and [(15)O]CO gasses could be produced in sufficient amounts, whilst meeting European Pharmacopeia requirements. Although produced oxygen-15 gasses contained a minor level of (11)C contamination, in clinical studies it was possible to correct for this contamination by delayed blood counting. CONCLUSION: An 11 MeV proton cyclotron combined with an in-house developed gas delivery system allows for the production and administration of sufficient amounts of [(15)O]-gasses for routine clinical PET studies in an hospital setting.

Effect of fluid loading with saline or colloids on pulmonary permeability, oedema and lung injury score after cardiac and major vascular surgery.

BACKGROUND: The optimal type of fluid for treating hypovolaemia without evoking pulmonary oedema is still unclear, particularly in the presence of pulmonary vascular injury, as may occur after cardiac and major vascular surgery. METHODS: In a single-centre, prospective, single-blinded clinical trial 67 mechanically ventilated patients were randomly assigned to receive saline, gelatin 4%, HES 6% or albumin 5%, according to a 90 min fluid loading protocol with target central venous pressure of 13 and pulmonary capillary wedge pressure of 15 mm Hg, within 3 h after cardiac or major vascular surgery. Before and after the protocol, we recorded haemodynamics and ventilatory variables and took chest radiographs. The pulmonary vascular injury was evaluated using the 67Ga-transferrin pulmonary leak index (PLI) and extravascular lung water (EVLW). Plasma colloid osmotic pressure (COP) was determined and the lung injury score (LIS) was calculated. RESULTS: More saline was infused than colloid solutions (P<0.005). The COP increased in the colloid groups and decreased in patients receiving saline. Cardiac output increased more in the colloid groups. At baseline, PLI and EVLW were above normal in 60 and 30% of the patients, with no changes after fluid loading, except for a greater PLI decrease in HES than in gelatin-loaded patients. The oxygenation ratio improved in all groups. In the colloid groups, the LIS increased, because of a decrease in total respiratory compliance, probably associated with an increase in intrathoracic plasma volume. CONCLUSIONS: Provided that fluid overloading is prevented, the type of fluid used for volume loading does not affect pulmonary permeability and oedema, in patients with acute lung injury after cardiac or major vascular surgery, except for HES that may ameliorate increased permeability. During fluid loading, changes in LIS (and respiratory compliance) do not represent changes in pulmonary permeability or oedema.

Pulmonary abnormalities after cardiac surgery are better explained by atelectasis than by increased permeability oedema.

BACKGROUND: Cardiac surgery can be complicated by pulmonary abnormalities, but it is unclear how various manifestations interrelate. METHODS: A prospective study in the intensive care unit was performed on 26 mechanically ventilated patients without cardiac failure within 3 h after elective cardiac surgery involving cardiopulmonary bypass. Oedema (extravascular lung water, EVLW) was measured by the thermal-dye technique and permeability by a dual radionuclide technique, yielding a pulmonary leak index (PLI). Radiographic, mechanical and gas exchange features were used to calculate the lung injury score (LIS), ranging between 0 and 4. Evidence for left lower lobe atelectasis was obtained from plain radiographs. The plasma colloid osmotic pressure (COP) was measured by an oncometer. RESULTS: The EVLW (normal, <7 ml/kg) was elevated in 36% of patients and the PLI (normal, <14.1 x 10(-3)/min) in 44%, but the variables did not interrelate directly. Patients with a supranormal EVLW had a lower COP than patients with normal EVLW. The duration of mechanical ventilation was prolonged in patients (20%) with EVLW > 10 ml/kg. There was no difference in EVLW and PLI in patients with LIS < 1 and LIS > 1 (31% of patients). In patients with radiographic evidence for atelectasis (46%), the positive end-expiratory pressure and inspiratory O2 fraction to maintain oxygenation were higher than in those without. CONCLUSIONS: After cardiac surgery, mild pulmonary oedema is relatively common, even in the absence of high filling pressures, and is mainly attributable to a low COP, irrespective of increased permeability in about one-half of patients. It may prolong mechanical ventilation at EVLW > 10 ml/kg. However, pulmonary radiographic and ventilatory abnormalities may result, at least in part, from atelectasis rather than increased permeability oedema.

Evaluation of pulmonary nodules: comparison of a prototype dual crystal (LSO/NAI) dual head coincidence camera and full ring positron emission tomography (PET).

PURPOSE: To determine the concordance of a prototype dual head coincidence camera (LSO-PS) and full ring PET (BGO-PET) using (18)F-fluorodeoxyglucose (FDG) in the evaluation of pulmonary nodules (PNs). MATERIALS AND METHODS: Patients referred for evaluation of < or =3 PNs (< or =3 cm diameter) were prospectively studied on the same day with both BGO-PET and LSO-PS. Imaging was performed at 60 and 120 min after injection of 370MBq FDG, respectively. Images were independently interpreted by four observers with each observer blinded to the other modality for the same patient. Lesions were scored in terms of relative intensity versus background. Non-attenuation corrected (nonAC) BGO-PET was used as the reference test. RESULTS: Forty-seven patients with 54 PNs (mean diameter 1.7 cm, S.D. 0.7) were included. Twelve nodules were in the < or =1.0 cm - 27 in the 1.1-2.0 cm - and 15 in the 2.1-3.0 cm range. Interobserver agreement was similar for both FDG imaging modalities. Using a sensitive assessment strategy with LSO-PS (> or = faint intensity deemed positive), there was a 97% (38/39, 95%CI 87-100%) concordance with BGO-PET and one false positive case with LSO-PS. Conservative reading (moderate or intense intensity deemed positive) resulted in a 92% (36/39, 95%CI 80-97%) concordance with BGO-PET, without false positives. The only lesion missed by LSO-PS using both assessment strategies involved a nodule 1.5 cm diameter that demonstrated moderate increased FDG uptake on BGO-PET. CONCLUSION: Depending on the test positivity criteria, LSO-PS demonstrates a high concordance (92-97%) with nonAC BGO-PET for the characterization of pulmonary nodules.

Optimization of attenuation correction for positron emission tomography studies of thorax and pelvis using count-based transmission scans.

The quality of thorax and pelvis transmission scans and therefore of attenuation correction in PET depends on patient thickness and transmission rod source strength. The purpose of the present study was to assess the feasibility of using count-based transmission scans, thereby guaranteeing more consistent image quality and more precise quantification than with fixed transmission scan duration. First, the relation between noise equivalent counts (NEC) of 10 min calibration transmission scans and rod source activity was determined over a period of 1.5 years. Second, the relation between transmission scan counts and uniform phantom diameter was studied numerically, determining the relative contribution of counts from lines of response passing through the phantom as compared with the total number of counts. Finally, the relation between patient weight and transmission scan duration was determined for 35 patients, who were scanned at the level of thorax or pelvis. After installation of new rod sources, the NEC of transmission scans first increased slightly (5%) with decreasing rod source activity and after 3 months decreased with a rate of 2-3% per month. The numerical simulation showed that the number of transmission scan counts from lines of response passing through the phantom increased with phantom diameter up to 7 cm. For phantoms larger than 7 cm, the number of these counts decreased at approximately the same rate as the total number of transmission scan counts. Patient data confirmed that the total number of transmission scan counts decreased with increasing patient weight with about 0.5% kg(-1). It can be concluded that count-based transmission scans compensate for radioactive decay of the rod sources. With count-based transmission scans, rod sources can be used for up to 1.5 years at the cost of a 50% increased transmission scan duration. For phantoms with diameters of more than 7 cm and for patients scanned at the level of thorax or pelvis, use of count-based transmission scans is feasible and results in statistically more consistent transmission scans as compared with fixed transmission scan duration.

Nuclear imaging is more sensitive for the detection of viable myocardium than dobutamine echocardiography.

Intact perfusion, preserved metabolism of free fatty acids and glucose, and the presence of contractile reserve have been used as markers of viable myocardium. However, not all viable myocardium may exhibit all these characteristics. Accordingly, these features were evaluated in patients with chronic coronary artery disease and left ventricular dysfunction. Fourteen patients with chronic ischaemic heart disease and depressed left ventricular function (LVEF 34+/-10%) perfusion was evaluated by early resting 201Tl single photon emission computed tomography (SPECT), fatty acid utilization by 15-p-[123I]iodophenyl-3-(R,S)-methylpentadecanoic acid SPECT, glucose utilization by 2-[18F]fluoro-2-deoxy-D-glucose SPECT and contractile reserve (CR) by dobutamine echocardiography. The comparison of the different modalities was restricted to akinetic or dyskinetic myocardium as assessed by resting 2-dimensional echocardiography. For all techniques a 13-segment model was used. Sixty-four of 182 segments (35%) showed akinesia or dyskinesia. Intact perfusion was found in 33/64 (52%) segments. Fatty acid utilization was maintained in 38/64 (59%) segments and glucose utilization was maintained in 38/64 (59%) segments. CR was present in significantly fewer segments: 21 of 64 (33%) (P<0.01 vs glucose and fatty acid utilization). In the 21 segments with preserved CR, perfusion was intact in 16/21 (76%) segments, fatty acid utilization in 19/21 (90%) segments and glucose utilization was preserved in all (100%) segments. Conversely, in the 43 segments without CR, 17 segments (40%) showed intact perfusion, 19 segments (44%) preserved fatty acid utilization and 17 (40%) still showed preserved glucose utilization. Disagreement in segments between the viability markers was caused mainly by segments without CR but preserved perfusion, fatty acid or glucose utilization. The substantial number of segments with preserved glucose and fatty acid utilization but without contractile reserve, suggests an underestimation of myocardial viability by dobutamine echocardiography.

How morphometric analysis of metastatic load predicts the (un)usefulness of PET scanning: the case of lymph node staging in melanoma.

BACKGROUND: In primary cutaneous melanoma, the sentinel node (SN) biopsy is an accurate method for the staging of the lymph nodes. Positron emission tomography (PET) has been suggested as a useful alternative. However, the sensitivity of PET may be too low to detect SN metastases, which are often small. AIM: To predict the value of PET for initial lymph node staging in melanoma based on morphometric analysis of SN metastatic load, without exposing patients to PET. MATERIALS AND METHODS: In 59 SN positive patients with melanoma, the sizes of tumour deposits in the SNs and subsequent dissection specimens were measured by morphometry and correlated with the detection limits of current and future PET scanners. RESULTS: The median tumour volume within the basin was 0.15 mm(3) (range, 0.0001-118.86). Seventy per cent of these deposits were smaller than 1 mm(3). State of the art PET scanners that have a resolution of about 5 mm would detect only 15-49% of positive basins. Logistic regression analysis revealed no pretest indicators identifying patients expected to have a positive PET. However, the SN tumour load was a significant and single predictor of the presence of PET detectable residual tumour. CONCLUSION: Morphometric analysis of metastatic load predicts that PET scanning is unable to detect most metastatic deposits in sentinel lymph nodes of patients with melanoma because the metastases are often small. Therefore, the SN biopsy remains the preferred method for initial regional staging.

Rapid evaluation of FDG imaging alternatives using head-to-head comparisons of full ring and gamma camera based PET scanners--a systematic review.

AIM: While FDG full ring PET (FRPET) has been gradually accepted in oncology, the role of the cheaper gamma camera based alternatives (GCPET) is less clear. Since technology is evolving rapidly, "tracker trials" would be most helpful to provide a first approximation of the relative merits of these alternatives. As difference in scanner sensitivity is the key variable, head-to-head comparison with FRPET is an attractive study design. This systematic review summarises such studies. METHODS: Nine studies were identified until July 1, 2000. Two observers assessed the methodological quality (Cochrane criteria), and extracted data. RESULTS: The studies comprised a variety of tumours and indications. The reported GC- and FRPET agreement for detection of malignant lesions ranged from 55 to 100%, but with methodological limitations (blinding, standardisation, limited patient spectrum). Mean lesion diameter was 2.9 cm (SD 1.8), with only about 20% < 1.5 cm. The 3 studies with the highest quality reported concordances of 74-79%, for the studied lesion spectrum. Contrast at GCPET was lower than that of FRPET, contrast and detection agreement were positively related. Logistic regression analysis suggested that pre-test indicators might be used to predict FRPET-GCPET concordance. CONCLUSION: In spite of methodological limitations, "first generation" GCPET devices detected sufficient FRPET positive lesions to allow prospective evaluation in clinical situations where the impact of FRPET is not confined to detection of small lesions (< 1.5 cm). The efficiency of head-to-head comparative studies would benefit from application in a clinically relevant patient spectrum, with proper blinding and standardisation of acquisition procedures.