Influence of TSH on uptake of [<Superscript>18</Superscript>F]fluorodeoxyglucose in human thyroid cells in vitro

Recent clinical evidence suggests that positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) is more accurate in detecting thyroid carcinomatous tissue at high than at low TSH levels. The aim of this study was to determine the influence of TSH on FDG uptake in human thyroid cells in vitro. Monolayers of human thyroid tissue were cultured after mechanical disintegration and enzymatic digestion of samples from patients undergoing surgery for nodular goitre. The purity of thyroid cell preparations was ascertained by immunohistochemical staining for the epithelial antigen KL-1, and their viability by measuring the synthesis of thyroglobulin in vitro. The cells were incubated with 0.8–1.5 MBq FDG/ml uptake medium for 1 h. FDG uptake in thyroid cells was quantified as percent of whole FDG activity per well (% ID) or as % ID in relation to total protein mass. This experimental protocol was subsequently varied to study the effect of incubation time, glucose dependency and TSH. Furthermore, radio-thin layer chromatography was used to identify intracellular FDG metabolites. FDG accumulated in the thyroid cells linearly with time, doubling roughly every 20 min. Uptake was competitively inhibited by unlabelled glucose and decreased to approximately 70% at 100 mg/dl glucose compared to the value measured in glucose-free medium. FDG was intracellularly trapped as FDG-6 phosphate and FDG-1,6-diphosphate. TSH significantly increased FDG uptake in vitro in a time- and concentration-dependent manner: Cells cultured at a TSH concentration of 50 µU/ ml doubled FDG uptake compared to TSH-free conditions, and uptake after 72 h of TSH pre-incubation was approximately 300% of that without TSH pre-incubation. TSH stimulates FDG uptake by benign thyroid cells in a time- and concentration-dependent manner. This supports the clinical evidence that in well-differentiated thyroid carcinomas, most of which are still TSH-sensitive, FDG-PET is more accurate at high levels of TSH.     

Preclinical in vivo and in vitro comparison of the translocator protein PET ligands [<Superscript>18</Superscript>F]PBR102 and [<Superscript>18</Superscript>F]PBR111

Purpose

To determine the metabolic profiles of the translocator protein ligands PBR102 and PBR111 in rat and human microsomes and compare their in vivo binding and metabolite uptake in the brain of non-human primates (Papio hamadryas) using PET-CT.

Methods

In vitro metabolic profiles of PBR102 and PBR111 in rat and human liver microsomes were assessed by liquid chromatography–tandem mass spectrometry. [¹⁸F]PBR102 and [¹⁸F]PBR111 were prepared by nucleophilic substitution of their corresponding p-toluenesulfonyl precursors with [¹⁸F]fluoride. List mode PET-CT brain imaging with arterial blood sampling was performed in non-human primates. Blood plasma measurements and metabolite analysis, using solid-phase extraction, provided the metabolite profile and metabolite-corrected input functions for kinetic model fitting. Blocking and displacement PET-CT scans, using PK11195, were performed.

Results

Microsomal analyses identified the O-de-alkylated, hydroxylated and N-de-ethyl derivatives of PBR102 and PBR111 as the main metabolites. The O-de-alkylated compounds were the major metabolites in both species; human liver microsomes were less active than those from rat. Metabolic profiles in vivo in non-human primates and previously published rat experiments were consistent with the microsomal results. PET-CT studies showed that K₁ was similar for baseline and blocking studies for both radiotracers; V_T was reduced during the blocking study, suggesting low non-specific binding and lack of appreciable metabolite uptake in the brain.

Conclusions

[¹⁸F]PBR102 and [¹⁸F]PBR111 have distinct metabolic profiles in rat and non-human primates. Radiometabolites contributed to non-specific binding and confounded in vivo brain analysis of [¹⁸F]PBR102 in rodents; the impact in primates was less pronounced. Both [¹⁸F]PBR102 and [¹⁸F]PBR111 are suitable for PET imaging of TSPO in vivo. In vitro metabolite studies can be used to predict in vivo radioligand metabolism and can assist in the design and development of better radioligands.

     

Multimodal correlation of dynamic [<Superscript>18</Superscript>F]-AV-1451 perfusion PET and neuronal hypometabolism in [<Superscript>18</Superscript>F]-FDG PET

Purpose

Cerebral glucose metabolism measured with [18F]-FDG PET is a well established marker of neuronal dysfunction in neurodegeneration. The tau-protein tracer [18F]-AV-1451 PET is currently under evaluation and shows promising results. Here, we assess the feasibility of early perfusion imaging with AV-1451 as a substite for FDG PET in assessing neuronal injury.

Methods

Twenty patients with suspected neurodegeneration underwent FDG and early phase AV-1451 PET imaging. Ten one-minute timeframes were acquired after application of 200 MBq AV-1451. FDG images were acquired on a different date according to clinical protocol. Early AV-1451 timeframes were coregistered to individual FDG-scans and spatially normalized. Voxel-wise intermodal correlations were calculated on within-subject level for every possible time window. The window with highest pooled correlation was considered optimal. Z-transformed deviation maps (ZMs) were created from both FDG and early AV-1451 images, comparing against FDG images of healthy controls.

Results

Regional patterns and extent of perfusion deficits were highly comparable to metabolic deficits. Best results were observed in a time window from 60 to 360 s (r = 0.86). Correlation strength ranged from r = 0.96 (subcortical gray matter) to 0.83 (frontal lobe) in regional analysis. ZMs of early AV-1451 and FDG images were highly similar.

Conclusion

Perfusion imaging with AV-1451 is a valid biomarker for assessment of neuronal dysfunction in neurodegenerative diseases. Radiation exposure and complexity of the diagnostic workup could be reduced significantly by routine acquisition of early AV-1451 images, sparing additional FDG PET.

     

Comparison of the biodistribution of two hypoxia markers [<Superscript>18</Superscript>F]FETNIM and [<Superscript>18</Superscript>F]FMISO in an experimental mammary carcinoma

The first aim of this study was to compare the hypoxia imaging ability of fluorine-18 fluoroerythronitroimidazole ([¹⁸F]FETNIM) with that of fluorine-18 fluoromisonimidazole ([¹⁸F]FMISO) in murine tumours of different sizes under two different oxygenation conditions. Secondly, we wanted to assess the biodistribution of the markers in normal tissues under similar conditions. Female CDF1 mice with a C3H mammary carcinoma grown on their backs were used. Tumours were size matched and animals breathed either normal air (21% O₂) or carbogen gas (95% O₂ + 5% CO₂). The gassing procedure was begun 5 min before the intravenous injection of either [¹⁸F]FETNIM or [¹⁸F]FMISO and continued until the mice were sacrificed at 120 min. Blood, tumour, muscle, heart, lung, liver, kidney and fat were removed, counted for radioactivity and weighed. The tumour and muscle were frozen and cut with a cryomicrotome into sections. The spatial distribution of radioactivity from the tissue sections was determined with digital autoradiography. Estimation of the necrotic fraction was made on sections from formalin-fixed tumours. Digital autoradiography showed that the whole tumour-to-muscle radioactivity uptake ratios were significantly higher in normal air-breathing mice than in carbogen-treated mice for both [¹⁸F]FETNIM (4.9±2.6 vs 1.8±0.5; P<0.01) and [¹⁸F]FMISO (4.4±1.0 vs 1.5±0.4; P<0.01). The carbogen treatment had only slight effects on the biodistribution of either marker in normal tissues. The necrotic fraction determined in tumours did not correlate with the tumour volume or with the tumour-to-muscle radioactivity uptake ratio. This study shows that the uptake of both [¹⁸F]FETNIM and [¹⁸F]FMISO correlates with the oxygenation status in tumours. In addition, our data show no significant difference in the intratumoral uptake between the two markers. However, significantly higher radioactivity uptake values were measured for [¹⁸F]FMISO than for [¹⁸F]FETNIM in normal tissues.     

Activity-based costing evaluation of [<Superscript>18</Superscript>F]-fludeoxyglucose production

Introduction As healthcare expenses are escalating in many countries, the sector faces a new challenge of becoming more cost efficient. There is an urgent need for more accurate data on the costs of healthcare procedures. The cost of Positron Emission Tomography (PET) with [¹⁸F]-fludeoxyglucose (¹⁸F-FDG) studies is mainly influenced by the price of the radiopharmaceutical, which may vary throughout Europe from 300 to 500 Euro per patient dose (370 MBq). The aim of the current study is to conduct an activity-based costing (ABC) estimation of ¹⁸F-FDG production in Europe to better identify the different cost components and to analyse their relative contribution to the total cost. Materials and methods Financial data were collected on capital expense and global operating costs through interviews with industry experts, PET centre managers, evaluation of prior studies, and review of expenses incurred at the University Medical Centre in Groningen (The Netherlands). After mapping the activities, we divided the cost in five categories: wage, equipment, consumables, overhead and space costs. A sensitivity analysis was performed for key cost components, including the compliance with regulatory requirements. Results The critical factor for profitability was throughput. Including the European regulation procedure, the cost for 370 MBq ¹⁸F-FDG patient dose, 3 h EOS without delivery cost, ranges between 155 and 177 Euro/dose for two production runs and between 210 and 237 Euro/dose for one production run. These costs are predominantly determined by personnel and equipment costs, although the cost for quality assurance increases steadily. Conclusion The ABC analysis provides significant insight into the production cost components of ¹⁸F-FDG through different operating configurations. Reductions in equipment prices, increased availability of radiopharmaceuticals, growth in demand, and improvements in reimbursement will all contribute to the financial viability of this imaging technique.     

Positron emission tomography with [<Superscript>18</Superscript>F]FDOPA and [<Superscript>18</Superscript>F]FDG in the imaging of small cell lung carcinoma: preliminary results

Small cell lung carcinomas (SCLC) express neuroendocrine markers, and dihydroxyphenylalanine (DOPA) is known to accumulate in neuroendocrine tumours. This study was performed with the aim of evaluating the uptake of 3,4-dihydroxy-6-¹⁸F-fluoro-phenylalanine ([¹⁸F]FDOPA) by SCLC, based on comparison with the results of fluorine-18 fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET) and standard imaging procedures. [¹⁸F]FDG PET and [¹⁸F]FDOPA PET were performed on four patients with newly diagnosed SCLC. There was agreement between the results of [¹⁸F]FDOPA PET and [¹⁸F]FDG PET in four tumoural sites out of 11, whereas [¹⁸F]FDG PET and standard imaging procedures were in full agreement. A semi-quantitative analysis based on standardised uptake values (SUVs) was performed in order to compare [¹⁸F]FDG and [¹⁸F]FDOPA tumour uptake. The median [¹⁸F]FDG SUV_max was 5.9 (with a 95% confidence interval from 4.4 to 9.2), while the median [¹⁸F]FDOPA SUV_max was 1.9 (with a 95% confidence interval from 1.6 to 3.8). The difference between [¹⁸F]FDG SUV_max and [¹⁸F]FDOPA SUV_max was significant (P<0.01). [¹⁸F]FDOPA PET appeared less sensitive than [¹⁸F]FDG PET and standard imaging procedures in the staging of SCLC. No clear relation between [¹⁸F]FDOPA uptake and positivity of neuroendocrine markers on immunohistochemistry emerged from these preliminary results; however, since [¹⁸F]FDOPA uptake may reflect better differentiation of the tumour, and possibly a better prognosis, this point warrants clarification in a larger study.     

[<Superscript>18</Superscript>F]Fluoroacetate is not a functional analogue of [<Superscript>11</Superscript>C]acetate in normal physiology

Purpose  [¹¹C]Acetate (C-AC) is a general PET tracer of cellular carbon flux and useful for clinical imaging in heart disease as well as prostate cancer and other tumours. C-AC has a high (70%) whole-body extraction fraction, proportional to blood flow in many organs. Trapping is related to organ-specific enzymatic activation and formation of [¹¹C]-acetyl-CoA, the fate of which has been well characterized. Due to the logistic challenges with C-AC, 2-[¹⁸F]fluoroacetate (F-AC) has been proposed as a marker for prostate cancer imaging. Method  We evaluated the potential of F-AC as a tracer for imaging blood flow and early enzymatic steps in the intermediary metabolism. C-AC and F-AC were injected serially in three cynomolgus monkeys and one domestic pig and scanned using PET/CT. A dynamic scan covering heart and liver was followed by repeated whole-body imaging. Kinetic patterns were compared for the myocardium, liver, blood and other organs. Results  C-AC kinetics and organ distribution in both species were similar to those previously established in man. In contrast, F-AC showed prolonged blood retention, no detectable trapping in myocardium or salivary glands, rapid clearance from liver and extensive excretion to bile and urine. Massive defluorination was seen in the pig, resulting in intense skeletal activity. Conclusion  2-[¹⁸F]Fluoroacetate cannot be regarded as a functional analogue of 1-[¹¹C]acetate in normal physiology and appears to be of little use for studies of organ blood flow, intermediary metabolism or lipid synthesis. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

[<Superscript>18</Superscript>F]EF3 is not superior to [<Superscript>18</Superscript>F]FMISO for PET-based hypoxia evaluation as measured in a rat rhabdomyosarcoma tumour model

Purpose  The aim of this investigation was to quantitatively compare the novel positron emission tomography (PET) hypoxia marker 2-(2-nitroimidazol-1-yl)-N-(3[¹⁸F],3,3-trifluoropropyl)acetamide ([¹⁸F]EF3) with the reference hypoxia tracer [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO). Methods  [¹⁸F]EF3 or [¹⁸F]FMISO was injected every 2 days into two separate groups of rats bearing syngeneic rhabdomyosarcoma tumours. In vivo PET analysis was done by drawing regions of interest on the images of selected tissues. The resulting activity data were quantified by the percentage of injected radioactivity per gram tissue (%ID/g) and tumour to blood (T/B) ratio. The spatial distribution of radioactivity was defined by autoradiography on frozen tumour sections. Results  The blood clearance of [¹⁸F]EF3 was faster than that of [¹⁸F]FMISO. The clearance of both tracers was slower in tumour tissue compared with other tissues. This results in increasing T/B ratios as a function of time post tracer injection (p.i.). The maximal [¹⁸F]EF3 tumour uptake, compared to the maximum [¹⁸F]FMISO uptake, was significantly lower at 2 h p.i. but reached similar levels at 4 h p.i. The tumour uptake for both tracers was independent of the tumour volume for all investigated time points. Both tracers showed heterogeneous intra-tumoural distribution. Conclusions  [¹⁸F]EF3 tumour uptake reached similar levels at 4 h p.i. compared with tumour retention observed after injection of [¹⁸F]FMISO at 2 h p.i. Although [¹⁸F]EF3 is a promising non-invasive tracer, it is not superior over [¹⁸F]FMISO for the visualisation of tumour hypoxia. No significant differences between [¹⁸F]EF3 and [¹⁸F]FMISO were observed with regard to the intra-tumoural distribution and the extra-tumoural tissue retention.     

Fast and repetitive in-capillary production of [<Superscript>18</Superscript>F]FDG

Purpose  The increasing demand for radiopharmaceuticals to be provided reproducibly and flexibly with high frequency for clinical application and animal imaging would be better met by improved or even new strategies for automated tracer production. Radiosynthesis in microfluidic systems, i.e. narrow tubing with a diameter of approximately 50–500 μm, holds promise for providing the means for repetitive multidose and multitracer production. In this study, the performance of a conceptually simple microfluidic device integrated into a fully automated synthesis procedure for in-capillary radiosynthesis (ICR) of clinical grade [¹⁸F]FDG was evaluated. Materials and methods  The instrumental set-up consisted of pumps for reagent and solvent delivery into small mixing chambers, μ-fluidic capillaries, in-process radioactivity monitoring, solid-phase extraction and on-column deprotection of the ¹⁸F-labelled intermediate followed by on-line formulation of [¹⁸F]FDG. Results  In-capillary¹⁸F-fluorination of 2.1 μmol 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulphonyl-beta-d-mannopyranose (TATM; precursor for [¹⁸F]FDG) in acetonitrile (MeCN) at a flow rate of 0.3 ml/min within 40 s and subsequent on-line hydrolysis of the intermediate by treatment with 0.3 M NaOH for 1 min at 40°C resulted in a radiochemical yield of 88 ± 4% within <7 min. Reproducibility, robustness and suitability as a fast and efficient radiopharmaceutical research tool for ¹⁸F-fluorination was demonstrated by eight independent, sequentially performed ICRs which provided identical tracer quality (radiochemical purity >97%, MeCN <5 μg/ml) and similar absolute yields (approximately 1.4 GBq). Conclusion  The described ICR process is a simple and efficient alternative to classic radiotracer production systems and provides a comparatively cheap instrumental methodology for the repetitive production of [¹⁸F]FDG with remarkably high efficiency and high yield under fully automated conditions. Although the results concerning the levels of activity need to be confirmed after installation of the equipment in a suitable GMP hot-cell environment, we expect the instrumental design to allow up-scaling without major difficulties or fundamental restrictions. Furthermore, we are convinced that similar or nearly identical procedures, and thus instrumentation, will allow ICR of other ¹⁸F-labelled radiopharmaceuticals. Hans-Jürgen Wester and Gjermund Henriksen contributed equally to the study reported here.     

[<Superscript>18</Superscript>F]FLT-PET in oncology: current status and opportunities

In recent years, [¹⁸F]-fluoro-3-deoxy-3-L-fluorothymidine ([¹⁸F]FLT) has been developed as a proliferation tracer. Imaging and measurement of proliferation with PET could provide us with a non-invasive staging tool and a tool to monitor the response to anticancer treatment. In this review, the basis of [¹⁸F]FLT as a proliferation tracer is discussed. Furthermore, an overview of the current status of [¹⁸F]FLT-PET research is given. The results of this research show that although [¹⁸F]FLT is a tracer that visualises cellular proliferation, it also has certain limitations. In comparison with the most widely used PET tracer, [¹⁸F]FDG, [¹⁸F]FLT uptake is lower in most cases. Furthermore, [¹⁸F]FLT uptake does not always reflect the tumour cell proliferation rate, for example during or shortly after certain chemotherapy regimens. The opportunities provided by, and the limitations of, [¹⁸F]FLT as a proliferation tracer are addressed in this review, and directions are given for further research, taking into account the strong and weak points of the new tracer.     

[<Superscript>18</Superscript>F]FLT PET for diagnosis and staging of thoracic tumours

The nucleoside analogue 3'-deoxy-3'-[¹⁸F]fluorothymidine (FLT) has been introduced for imaging of tumour cell proliferation by positron emission tomography (PET). This study evaluated the use of FLT in patients with thoracic tumours prior to treatment. Whole-body FLT PET was performed in 16 patients with 18 tumours [17 thoracic tumours (nine non-small cell lung cancers, five oesophageal carcinomas, two sarcomas, one Hodgkin's lymphoma) and one renal carcinoma] before treatment. Fluorine-18 fluorodeoxyglucose (FDG) PET was performed for comparison except in those patients with oesophageal carcinoma. For semi-quantitative analysis, the average and maximum standardised uptake values (avgSUV and maxSUV, respectively) (FLT, 114±20 min p.i.; FDG, 87±8 min p.i.; 50% isocontour region of interest) was calculated. All 17 thoracic tumours and 19/20 metastases revealed significant FLT accumulation, resulting in easy delineation from surrounding tissue. The additional small grade 1 renal carcinoma was not detected with either FLT or FDG. In most lung tumours (avgSUV 1.5–8.2) and metastases, FLT showed intense uptake. However, one of two spinal bone metastases was missed owing to the high physiological FLT uptake in the surrounding bone marrow. Oesophageal carcinoma primaries (avgSUV 2.7–10.0) and occasional metastases showed particularly favourable tumour/non-tumour contrast. Compared with FDG, tumour uptake of FLT was lower (avgSUV, P=0.0006; maxSUV, P=0.0001), with a significant linear correlation (avgSUV, r²=0.45; maxSUV, r²=0.49) between FLT and FDG. It is concluded that FLT PET accurately visualises thoracic tumour lesions. In the liver and the bone marrow, high physiological FLT uptake hampers detection of metastases. On the other hand, FLT may be favourable for imaging of brain metastases owing to the low physiological uptake.     

Prognostic value of [<Superscript>18</Superscript>F]FDG-PET imaging in small cell lung cancer

Positron emission tomography (PET) utilizing fluorine-18 fluorodeoxyglucose (FDG) has been used in the evaluation of non-small cell lung cancer (NSCLC). Recently its use in the staging of small cell lung cancer (SCLC) has been reported. However, the prognostic value of FDG-PET imaging in SCLC has not been studied. We performed a retrospective analysis to assess this, with the following hypotheses: (1) PET-positive patients would have a less favorable prognosis than PET-negative patients and (2) a high standardized uptake value (SUV) would be associated with a poor prognosis. Retrospective review of a mixed population of treated and untreated patients imaged between 1995 and 2000 was performed. Results of 62 scans in 46 patients were analyzed. There were 8 untreated and 38 treated patients. Findings were correlated with pathology, computed tomography/magnetic resonance imaging and clinical data. The sensitivity of PET scanning was 100% with pathological correlation. The prognostic value of a positive PET study was determined. Overall survival in PET-positive cases was significantly worse than that in PET-negative cases ( P=0.0108). Correlation of SUV(max) with survival showed a significant negative correlation ( P=0.0021). In the eight untreated patients, scans were strongly positive and in all cases the scan results concurred with the final clinical stage assigned on the basis of conventional methods. We conclude that FDG-PET imaging provides prognostic information in treated patients. A positive study and a high SUV(max) are significantly associated with poor survival. Additionally, FDG-PET may be helpful in staging and follow-up.     

Quantifying [<Superscript>18</Superscript>F]fluorodeoxyglucose uptake in the arterial wall: the effects of dual time-point imaging and partial volume effect correction

Purpose

The human arterial wall is smaller than the spatial resolution of current positron emission tomographs. Therefore, partial volume effects should be considered when quantifying arterial wall ¹⁸F-FDG uptake. We evaluated the impact of a novel method for partial volume effect (PVE) correction with contrast-enhanced CT (CECT) assistance on quantification of arterial wall ¹⁸F-FDG uptake at different imaging time-points.

Methods

Ten subjects were assessed by CECT imaging and dual time-point PET/CT imaging at approximately 60 and 180 min after ¹⁸F-FDG administration. For both time-points, uptake of ¹⁸F-FDG was determined in the aortic wall by calculating the blood pool-corrected maximum standardized uptake value (cSUV_MAX) and cSUV_MEAN. The PVE-corrected SUV_MEAN (pvcSUV_MEAN) was also calculated using ¹⁸F-FDG PET/CT and CECT images. Finally, corresponding target-to-background ratios (TBR) were calculated.

Results

At 60 min, pvcSUV_MEAN was on average 3.1 times greater than cSUV_MAX (P?<?.0001) and 8.5 times greater than cSUV_MEAN (P?<?.0001). At 180 min, pvcSUV_MEAN was on average 2.6 times greater than cSUV_MAX (P?<?.0001) and 6.6 times greater than cSUV_MEAN (P?<?.0001).

Conclusion

This study demonstrated that CECT-assisted PVE correction significantly influences quantification of arterial wall ¹⁸F-FDG uptake. Therefore, partial volume effects should be considered when quantifying arterial wall ¹⁸F-FDG uptake with PET.

     

Quantitative and qualitative analysis of [<Superscript>18</Superscript>F]FDG and [<Superscript>18</Superscript>F]FAZA positron emission tomography of head and neck cancers and associations with HPV status and treatment outcome

Purpose

While methods for imaging tumor hypoxia with positron emission tomography (PET) have been developed, optimal methods for interpreting and utilizing these datasets in the clinic remain unclear. In this study, we analyzed hypoxia PET images of head and neck cancer patients and compared imaging metrics with human papilloma virus (HPV) status and clinical outcome.

Methods

Forty-one patients treated as part of a phase III trial of the hypoxic cytotoxin tirapazamine (TROG 02.02) were imaged with PET using fluorodeoxyglucose (FDG) and fluoroazomycin arabinoside (FAZA). FDG and FAZA PET images were interpreted qualitatively and quantitatively, and compared with tumor T stage, HPV status, and treatment outcome using multivariate statistics.

Results

PET signals in the tumor and lymph nodes exhibited significant intra- and inter-patient variability. The FAZA hypoxic volume demonstrated a significant correlation with tumor T stage. PET-hypoxic tumors treated with cisplatin exhibited significantly worse treatment outcomes relative to PET-oxic tumors or PET-hypoxic tumors treated with tirapazamine.

Conclusion

Quantitative analysis of FAZA PET yielded metrics that correlated with clinical T stage and were capable of stratifying patient outcome. These results encourage further development of this technology, with particular emphasis on establishment of robust quantitative methods.

     

Quantification of receptor-ligand binding with [<Superscript>18</Superscript>F]fluciclatide in metastatic breast cancer patients

Purpose  

The purpose of the study was to estimate the receptor-ligand binding of an arginine-glycine-aspartic acid (RGD) peptide in somatic tumours. To this aim, we employed dynamic positron emission tomography (PET) data obtained from breast cancer patients with metastases, studied with the α_vβ_3/5 integrin receptor radioligand [¹⁸F]fluciclatide.     

Evaluation of high-risk melanoma: comparison of [<Superscript>18</Superscript>F]FDG PET and high-dose <Superscript>67</Superscript>Ga SPET

Recently the potential of whole-body positron emission tomography scanning using 18F-fluorodeoxyglucose (FDG PET) has led to renewed interest in the use of functional imaging for the detection of occult metastatic melanoma. This study compared dedicated FDG PET with high-dose gallium-67 imaging incorporating whole-body scanning and comprehensive single-photon emission tomography (SPET) in 122 cases (121 patients) in which the two scans were performed <6 weeks apart. All patients were at high clinical risk of occult metastatic disease and 49 (40%) had abnormality suggestive of metastatic disease by at least one functional imaging technique. Discrepant scan findings were followed up to determine which technique more accurately reflected disease status. There were 23/122 (19%; 95% CI: 12%-26%) cases with discordant scan results in respect of either the presence of melanoma (11 cases) or the extent of disease (12 cases). PET correctly identified more disease than 67Ga SPET in 14 cases (including three incidental primary tumours) and was true negative in three further patients with abnormal 67Ga SPET. There were six patients with true positive 67Ga SPET in whom FDG PET was false negative (one small cutaneous deposit, one residual axillary node rated equivocal on FDG PET due to postoperative changes, one adrenal metastasis inseparable from renal activity on FDG PET and three cases in which sites missed on FDG PET were seen on 67Ga SPET. Thus, FDG PET provided incremental diagnostic information compared with 67Ga SPET in 17/23 patients, while 67Ga SPET provided incremental information compared with PET in 6/23 cases ( P=0.035). Based on Australian Medicare reimbursement levels, the net cost per patient with clinical management benefit of replacing 67Ga SPET with FDG PET was estimated to be less than EUR 1,750. These results suggest that FDG PET provides incremental and clinically important information in around 10% of patients at a low incremental cost which, combined with greater patient convenience and lower radiation dosimetry, make FDG PET the functional imaging technique of choice for evaluation of suspected metastatic melanoma.     

Potential impact of [<Superscript>18</Superscript>F]3'-deoxy-3'-fluorothymidine versus [<Superscript>18</Superscript>F]fluoro-2-deoxy-<Emphasis Type="SmallCaps">d</Emphasis>-glucose in positron emission tomography for colorectal cancer

Ohne Zusammenfassung     

Impact of [<Superscript>18</Superscript>F]FDG-PET on the primary staging of small-cell lung cancer

Purpose The purpose of this study was to evaluate the impact of [¹⁸F]fluorodeoxy-d-glucose positron emission tomography (FDG-PET) on the primary staging of patients with small-cell lung cancer (SCLC).Methods FDG-PET was performed in 120 consecutive patients with SCLC during primary staging. In addition, brain examinations with both FDG-PET and cranial magnetic resonance imaging (MRI) or computed tomography (CT) were performed in 91 patients. Results of FDG-PET were compared with those of conventional staging procedures. FDG-PET detected markedly increased FDG uptake in the primary tumours of all 120 patients (sensitivity 100%).Results Complete agreement between FDG-PET results and other staging procedures was observed in 75 patients. Differences occurred in 45 patients at 65 sites. In 47 sites the FDG-PET results were proven to be correct, and in ten, incorrect. In the remaining eight sites, the discrepancies could not be clarified. In 14/120 patients, FDG-PET caused a stage migration, correctly upstaging ten patients to extensive disease and downstaging three patients by not confirming metastases of the adrenal glands suspected on the basis of CT. Only 1/120 patients was incorrectly staged by FDG-PET, owing to failure to detect brain metastases. In all cases the stage migration led to a significant change in the treatment protocol. Sensitivity of FDG-PET was significantly superior to that of CT in the detection of extrathoracic lymph node involvement (100% vs 70%, specificity 98% vs 94%) and distant metastases except to the brain (98% vs 83%, specificity 92% vs 79%). However, FDG-PET was significantly less sensitive than cranial MRI/CT in the detection of brain metastases (46% vs 100%, specificity 97% vs 100%).Conclusion The introduction of FDG-PET in the diagnostic evaluation of SCLC will improve the staging results and affect patient management, and may reduce the number of tests and invasive procedures.     

Quantification of [<Superscript>18</Superscript>F]-FDG uptake in atherosclerotic plaque: impact of renal function

Objective  

Impaired renal function causes both increased and prolonged tracer availability in the blood-pool which might result in increased tracer accumulation in atherosclerotic lesions. Therefore, the aim of this study was to investigate a possible correlation between the intensity of tracer uptake in atherosclerotic lesions and renal function.