<Superscript>18</Superscript>F-DOPA positron emission tomography for the detection of glomus tumours

The purpose of this study was to evaluate (18)F-DOPA whole-body positron emission tomography ((18)F-DOPA PET) as a biochemical imaging approach for the detection of glomus tumours. (18)F-DOPA PET and magnetic resonance imaging (MRI) were performed in ten consecutive patients with proven mutations of the succinate dehydrogenase subunit D ( SDHD) gene predisposing to the development of glomus tumours and other paragangliomas. (18)F-DOPA PET and MRI were performed according to standard protocols. Both methods were assessed under blinded conditions by two experienced specialists in nuclear medicine (PET) and diagnostic radiology (MRI). Afterwards the results were compared. A total of 15 lesions (four solitary and four multifocal tumours, the latter including 11 lesions) were detected by (18)F-DOPA PET. Under blinded conditions, (18)F-DOPA PET and MRI revealed full agreement in seven patients, partial agreement in two and complete disagreement in one. Eleven of the 15 presumed tumours diagnosed by (18)F-DOPA PET were confirmed by MRI. The correlation of (18)F-DOPA PET and MRI confirmed three further lesions previously only detected by PET. All of them were smaller than 1 cm and had the signal characteristics of lymph nodes. For one small lesion diagnosed by PET, no morphological MRI correlate could be found even retrospectively. No tumour was detected by MRI that was negative on (18)F-DOPA PET. All tumours diagnosed by MRI showed a hyperintense signal on T2-weighted images and a distinct enhancement of contrast medium on T1-weighted images. The mean tumour size was 1.5+/-0.5 cm. (18)F-DOPA PET seems to be a highly sensitive metabolic imaging procedure for the detection of glomus tumours and may have potential as a screening method for glomus tumours in patients with SDHD gene mutations.     

Direct comparison of FP-CIT SPECT and F-DOPA PET in patients with Parkinson’s disease and healthy controls

Purpose  Diagnosing Parkinson’s disease (PD) on clinical grounds may be difficult, especially in the early stages of the disease. F-DOPA PET and FP-CIT SPECT scans are able to determine presynaptic dopaminergic activity in different ways. The aim of this study was to determine and compare the sensitivity and specificity of the two methods in the detection of striatal dopaminergic deficits in the same cohort of PD patients and healthy controls. Methods  Movement disorder specialists recruited 11 patients with early-stage PD and 17 patients with advanced PD. The patients underwent both an FP-CIT SPECT scan and an F-DOPA PET scan. In addition, 10 FP-CIT SPECT scans or 10 F-DOPA PET scans were performed in 20 healthy controls. A template with regions of interest was used to sample tracer activity of the caudate, putamen and a reference region in the brain. The outcome parameter was the striatooccipital ratio (SOR). Normal SOR values were determined in the controls. The sensitivity and specificity of both scanning methods were calculated. Results  FP-CIT SPECT and F-DOPA PET scans were both able to discriminate PD patients from healthy controls. For the early phases of the disease, sensitivity and specificity of the contralateral striatal and putaminal uptake of FP-CIT and F-DOPA was 100%. When only caudate uptake was considered, the specificities were 100% and 90% for FP-CIT and F-DOPA, respectively, while the sensitivity was 91% for both scanning techniques. Conclusion  FP-CIT SPECT and F-DOPA PET scans are both able to diagnose presynaptic dopaminergic deficits in early phases of PD with excellent sensitivity and specificity.     

帕金森病脑部葡萄糖代谢和脑多巴胺转运体PET显像特点的临床研究

目的 探讨18F-FDG脑代谢联合11C-甲基-N-2β-甲基酯-3β（4-F苯基）托烷（11C-CFT）脑多巴胺转运体（DAT）PET双显像在帕金森病（PD）诊断与病情严重程度评估中的应用价值。 方法 对55例不同严重程度的PD患者及30名健康对照者分别行18F-FDG脑代谢显像和11C-CFT脑DAT PET显像检查,通过勾画ROI,比较PET图像中不同严重程度的PD患者与健康对照者中脑基底节区葡萄糖代谢及DAT分布的差异,分析18F-FDG PET、11C-CFT PET显像在不同严重程度PD评估中的作用及特点。 结果 与健康对照者相比,18F-FDG PET显像中PD患者脑葡萄糖代谢改变主要为双侧基底节区壳核对称性代谢增高,同时部分患者伴有大脑皮质不同程度代谢减低;11C-CFT PET显像中PD患者双侧尾状核、壳核前、中、后部表现为DAT分布不同程度减低。单侧症状者或双侧症状者均以患侧对侧基底节区壳核DAT分布减低明显,并以壳核后部DAT分布减低为著。 结论 18F-FDG PET联合11C-CFT PET双显像在PD诊断及病情严重程度评估中有应用价值。     

Crossover study of (99m)Tc-TRODAT-1 SPECT and (18)F-FDOPA PET in Parkinson's disease patients.

99mTc-TRODAT-1 ([2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)]) is a potential agent for dopamine transporter (DAT) SPECT, whereas 6-(18)F-fluoro-L-dopa ((18)F-FDOPA) PET has been used for the quantitative assessment of presynaptic nigrostriatal dopaminergic function. The current study investigated the relationship between the 2 imaging modalities in evaluating patients with Parkinson's disease (PD). METHODS: Twenty patients in whom PD was diagnosed by generally accepted criteria were recruited. In addition to visual inspection, specific uptake ratios (SURs) of (99m)Tc-TRODAT-1 in the striatum and putamen were measured bilaterally. For PET, all patients received 100 mg of carbidopa 90 min before (18)F-FDOPA (300 MBq) injection. Images were acquired between 120 and 150 min after injection, using a whole-body PET scanner with settings identical to those for the SPECT studies. The SURs for PET were calculated similarly to those for SPECT. Individual SURs of the striatum or putamen from SPECT were correlated with the corresponding PET values using linear regression. RESULTS: A consistent image pattern between SPECT and PET was achieved by visual inspection except for 3 cases. In 1 case (a patient with Hoehn and Yahr Scale I PD), the SPECT images were more compatible with the patient's clinical findings whereas PET showed nearly normal uptake. In the other 2 cases (both patients with Hoehn and Yahr Scale II PD), PET correlated better with the clinical findings. The caudate and putamen nuclei were more discernable on PET. An acceptable correlation of SUR, however, was found between SPECT and PET in both the striatum and the putamen (P < 0.01 for both). CONCLUSION: The comparability of (99m)Tc-TRODAT-1 SPECT and (18)F-FDOPA PET suggests that (99m)Tc-TRODAT-1 SPECT may provide a reliable alternative to (18)F-FDOPA PET in the evaluation of clinical PD patients.     

Comparative analysis of striatal FDOPA uptake in Parkinson's disease: ratio method versus graphical approach.

Striatal-to-occipital ratio (SOR) and influx constant K(i)(occ) are commonly used as analytic parameters in L-3,4-dihydroxy-6-(18)F-fluorophenylalanine (FDOPA) PET studies. Both have been shown to be useful in discriminating Parkinson's disease (PD) patients from healthy subjects. We evaluated the relative performance of SOR and influx constant (K(i)(occ)) in the clinical assessment of nigrostriatal dopaminergic function in PD. METHODS: Twenty-one parkinsonian patients (Hoehn and Yahr scale I-IV; mean age +/- SD, 56 +/- 9.2 y) and 11 healthy subjects (mean age, 60 +/- 16 y) underwent 3-dimensional dynamic FDOPA scanning from 0 to 100 min. After spatial realignment, PET images at each frame were integrated by summing 4 central striatal slices, and time-activity curves (TACs) were generated after placing a standard set of elliptic regions of interest over striatal and occipital structures. SOR and K(i)(occ) values for each subject were then computed from TACs at different times using an input function from the occipital cortex. RESULTS: Both SOR and K(i)(occ) showed significant bilateral decreases in striatal dopamine uptake in the PD group compared with the control group. SOR values estimated for 10-min frames between 65 and 95 min are statistically equivalent in group discrimination. In addition, SOR values in the caudate and putamen correlated strongly with K(i)(occ), especially toward the end of the scanning epoch. Both parameters correlated significantly and comparably with Unified Parkinson's Disease Rating Scale motor scores. CONCLUSION: These results suggest that SOR determined from a single 10-min scan at 95 min is as accurate as K(i)(occ) in separating PD patients from healthy subjects and in predicting clinical measures of disease severity.     

Accuracy of F-DOPA PET and perfusion-MRI for differentiating radionecrotic from progressive brain metastases after radiosurgery

Purpose

We assessed the performance of 6-[¹⁸F]-fluoro-l-3,4-dihydroxyphenylalanine (F-DOPA) PET for differentiating radionecrosis (RN) from tumour progression (PD) in a population of patients with brain metastases, treated with stereotactic radiosurgery. The accuracy of F-DOPA PET was compared with that of perfusion-weighted magnetic resonance (perfusion-MR).

Methods

In 42 patients with a total of 50 brain metastases from various primaries F-DOPA PET/CT was performed because of suspected radiological progression at the site of previously irradiated brain metastasis. Several semiquantitative PET parameters were recorded, and their diagnostic accuracy was compared by receiver operating characteristic curve analyses. The diagnosis was established by either surgery or follow-up. A comparison was made between F-DOPA PET and perfusion-MR sequences acquired no more than 3 weeks apart.

Results

Definitive outcome was available in 46 of the 50 lesions (20 PD, 26 RN). Of the 46 lesions, 11 were surgically excised while in the remaining 35 lesions the diagnosis was established by radiological and clinical criteria. The best diagnostic performance was obtained using the semiquantitative PET parameter maximum lesion to maximum background uptake ratio (SUVL_max/Bkgr_max). With a cut-off value of 1.59, a sensitivity of 90 % and a specificity of 92.3 % were achieved in differentiating RN from PD lesions (accuracy 91.3 %). Relative cerebral blood volume (rCBV) derived from perfusion-MR was available for comparison in 37 of the 46 metastases. Overall accuracy of rCBV was lower than that of all semiquantitative PET parameters under study. The best differentiating rCBV cut-off value was 2.14; this yielded a sensitivity of 86.7 % and a specificity of 68.2 % (accuracy 75.6 %).

Conclusion

F-DOPA PET is a highly accurate tool for differentiating RN from PD brain metastases after stereotactic radiosurgery. In this specific setting, F-DOPA PET seems to perform better than perfusion-MR.

     

The effects of carbidopa on uptake of 6-18F-Fluoro-L-DOPA in PET of pheochromocytoma and extraadrenal abdominal paraganglioma.

6-(18)F-fluoro-l-3,4-dihydroxyphenylalanine ((18)F-DOPA) PET is a useful tool for the detection of certain neuroendocrine tumors, especially with the preadministration of carbidopa, an inhibitor of DOPA decarboxylase. Whether carbidopa also improves (18)F-DOPA PET of adrenal pheochromocytomas and extraadrenal paragangliomas is unknown. The aim of this study was to investigate the sensitivity of (18)F-DOPA PET in the detection of paraganglioma and its metastatic lesions and to evaluate whether tracer uptake by the tumors is enhanced by carbidopa. METHODS: Two patients with nonmetastatic adrenal pheochromocytoma, and 9 patients with extraadrenal abdominal paraganglioma (1 nonmetastatic, 8 metastatic), underwent whole-body CT, MRI, baseline (18)F-DOPA PET, and (18)F-DOPA PET with oral preadministration of 200 mg of carbidopa. The dynamics of tracer uptake by these lesions and the physiologic distribution of (18)F-DOPA in normal tissues were recorded. RESULTS: Seventy-eight lesions were detected by CT or MRI, 54 by baseline (18)F-DOPA PET (P = 0.0022 vs. CT/MRI), and 57 by (18)F-DOPA PET plus carbidopa (P = 0.0075 vs. CT/MRI, not statistically significant vs. baseline). In reference to findings on CT and MRI, the sensitivities of baseline (18)F-DOPA PET were 47.4% for lesions and 55.6% for positive body regions, versus 50.0% (lesions) and 66.7% (regions) for (18)F-DOPA PET plus carbidopa (neither is statistically significant vs. baseline). Compared with baseline, carbidopa detected additional lesions in 3 (27%) of 11 patients. Carbidopa increased the mean (+/-SD) peak standardized uptake value in index tumor lesions from 6.4 +/- 3.9 to 9.1 +/- 5.6 (P = 0.037). Pancreatic physiologic (18)F-DOPA uptake, which may mask adrenal pheochromocytoma, is blocked by carbidopa. CONCLUSION: Carbidopa enhances the sensitivity of (18)F-DOPA PET for adrenal pheochromocytomas and extraadrenal abdominal paragangliomas by increasing the tumor-to-background ratio of tracer uptake. The sensitivity of (18)F-DOPA PET for metastases of paraganglioma appears to be limited.     

Diagnostic performance of 18F-dihydroxyphenylalanine positron emission tomography in patients with paraganglioma: a meta-analysis

Purpose

The aim of this study was to systematically review and conduct a meta-analysis of published data about the diagnostic performance of ¹⁸F-dihydroxyphenylalanine (DOPA) positron emission tomography (PET) in patients with paraganglioma (PG).

Methods

A comprehensive computer literature search of studies published through 30 June 2011 regarding ¹⁸F-DOPA PET or PET/computed tomography (PET/CT) in patients with PG was performed in PubMed/MEDLINE, Embase and Scopus databases. Pooled sensitivity and specificity of ¹⁸F-DOPA PET or PET/CT in patients with PG on a per patient- and on a per lesion-based analysis were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of ¹⁸F-DOPA PET or PET/CT in patients with PG. Furthermore, a sub-analysis taking into account the different genetic mutations in PG patients was also performed.

Results

Eleven studies comprising 275 patients with suspected PG were included in this meta-analysis. The pooled sensitivity of ¹⁸F-DOPA PET and PET/CT in detecting PG was 91% [95% confidence interval (CI) 87–94%] on a per patient-based analysis and 79% (95% CI 76–81%) on a per lesion-based analysis. The pooled specificity of ¹⁸F-DOPA PET and PET/CT in detecting PG was 95% (95% CI 86–99%) on a per patient-based analysis and 95% (95% CI 84–99%) on a per lesion-based analysis. The area under the ROC curve was 0.95 on a per patient- and 0.94 on a per lesion-based analysis. Heterogeneity between the studies about sensitivity of ¹⁸F-DOPA PET or PET/CT was found. A significant increase in sensitivity of ¹⁸F-DOPA PET or PET/CT was observed when a sub-analysis excluding patients with succinate dehydrogenase subunit B (SDHB) gene mutations was performed.

Conclusion

In patients with suspected PG ¹⁸F-DOPA PET or PET/CT demonstrated high sensitivity and specificity. ¹⁸F-DOPA PET or PET/CT are accurate methods in this setting. Nevertheless, possible sources of false-negative results should be kept in mind. Furthermore, SDHB gene mutations could influence ¹⁸F-DOPA PET or PET/CT diagnostic performance.     

Clinical value of 18F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography (18F-DOPA PET/CT) for detecting pheochromocytoma

Purpose

In detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor ¹⁸F-fluorodihydroxyphenylalanine (¹⁸F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined ¹⁸F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone.

Methods

¹⁸F-DOPA PET, CT and ¹⁸F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology.

Results

Of the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of ¹⁸F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value.

Conclusion

¹⁸F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do ¹⁸F-DOPA PET or CT alone.     

Ability of <Superscript>18</Superscript>F-DOPA PET/CT and fused <Superscript>18</Superscript>F-DOPA PET/MRI to assess striatal involvement in paediatric glioma

Purpose

To assess the diagnostic performance of ¹⁸F-DOPA PET/CT and fused ¹⁸F-DOPA PET/MRI in detecting striatal involvement in children with gliomas.

Methods

This retrospective study included 28 paediatric patients referred to our institution for the presence of primary, residual or recurrent glioma (12 boys, 16 girls; mean age 10.7 years) and investigated with ¹⁸F-DOPA PET/CT and brain MRI. Fused ¹⁸F-DOPA PET/MR images were obtained and compared with PET/CT and MRI images. Accuracy, sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for striatal involvement were calculated for each diagnostic tool. Univariate and multivariate logistic analyses were applied to evaluate the associations between ¹⁸F-DOPA PET/CT and fused ¹⁸F-DOPA PET/MRI diagnostic results and tumour uptake outside the striatum, grade, dimension and site of striatal involvement (ventral and/or dorsal).

Results

Accuracy, sensitivity, specificity, PPV, and NPV were 100 % for MRI, 93 %, 89 %, 100 %, 100 % and 82 % for ¹⁸F-DOPA PET/MRI, and 75 %, 74 %, 78 %, 88 % and 58 % for ¹⁸F-DOPA PET/CT, respectively. ¹⁸F-DOPA PET/MRI showed a trend towards higher accuracy compared with ¹⁸F-DOPA PET/CT (p?=?0.06). MRI showed significantly higher accuracy compared with ¹⁸F-DOPA PET/CT (p?=?0.01), but there was no significant difference between MRI and ¹⁸F-DOPA PET/MRI. Both univariate and multivariate logistic analyses showed a significant association (OR 8.0 and 7.7, respectively) between the tumour-to-normal striatal uptake (T/S) ratio and the diagnostic ability of ¹⁸F-DOPA PET/CT (p?=?0.03). A strong significant association was also found between involvement of the dorsal striatum and the ¹⁸F-DOPA PET/CT results (p?=?0.001), with a perfect prediction of involvement of the dorsal striatum by ¹⁸F-DOPA PET/MRI.

Conclusion

Physiological striatal ¹⁸F-DOPA uptake does not appear to be a main limitation in the evaluation of basal ganglia involvement.¹⁸F-DOPA PET/CT correctly detected involvement of the dorsal striatum in lesions with a T/S ratio >1, but appeared to be less suitable for evaluation of the ventral striatum. The use of fused ¹⁸F-DOPA PET/MRI further improves the accuracy and is essential for evaluation of the ventral striatum.

     

Clinical Significance of F-18 FP-CIT Dual Time Point PET Imaging in Idiopathic Parkinson’s Disease

Purpose

The purpose of this study was to investigate the diagnostic value of dual time point F-18 FP-CIT PET imaging in idiopathic Parkinson’s disease (PD).

Materials and Methods

Twenty-four patients with PD (mean age 69.6) and 18 healthy people (mean age 70.26) underwent two sequential PET/CT scans (dual time point imaging) at 90 and 210 min after F-18 FP-CIT injection. Tracer activity of region of interest was measured in the caudate, putamen and a reference region in the brain from both time points. The outcome parameter was the striatooccipital ratio (SOR). Normal SOR values were obtained in the control group. The percent change in tracer activity between 90- and 210-min images was calculated. The SOR values and the percent change in tracer activity were compared between the patients and healthy control group.

Results

The SOR values for the caudate, anterior and posterior putamen at both 90- and 210-min images were significantly reduced in the patients with PD. The lowest P value was obtained for the anterior and posterior putamen (p < 0.001) at both time points. There were significant differences of the percent change in tracer activity for the anterior and posterior putamen in the two groups (p = 0.01).

Conclusions

F-18 FP-CIT PET scans at 90 and 210 min after injection are both able to diagnose PD. Therefore, the 90-min image by itself is sufficient for diagnosing PD.     

18F-DOPA positron emission tomography for tumour detection in patients with medullary thyroid carcinoma and elevated calcitonin levels

In spite of the availability of numerous procedures, diagnostic imaging of tumour manifestations in patients with medullary thyroid carcinoma and elevated calcitonin levels is often difficult. In the present study, the new procedure of fluorine-18 dihydroxyphenylalanine positron emission tomography (18F-DOPA PET) was compared with the established functional and morphological imaging methods. After evaluation of the normal distribution of 18F-DOPA, 11 patients with medullary thyroid carcinoma were examined using 18F-DOPA PET. Results of 18F-fluorodeoxyglucose (18F-FDG) PET, somatostatin receptor scintigraphy (SRS) and morphological tomographic imaging (CT/MRI) were available for all patients. All individual procedures were evaluated without reference to prior information. Data assessment for each patient was based on cooperation between experienced radiologists and specialists in nuclear medicine, who considered all the available findings (histological results, imaging, follow-up studies). This cooperation served as the gold standard against which the results of the individual procedures were evaluated. A total of 27 tumours were studied [three primary tumours (PT)/local recurrence (LR), 16 lymph node metastases (LNM) and eight organ metastases (OM)]. 18F-DOPA PET produced 17 true-positive findings (2 PT/LR, 14 LNM, 1 OM), 18F-FDG PET 12 (2 PT/LR, 7 LNM, 3 OM), SRS 14 (2 PT/LR, 8 LNM, 4 OM) and morphological imaging 22 (3 PT/LR, 11 LNM, 8 OM). The following sensitivities were calculated with respect to total tumour manifestations: 18F-DOPA PET 63%, 18F-FDG PET 44%, SRS 52%, morphological imaging 81%. Thus, the morphological imaging procedures produce the best overall sensitivity, but the specificity for PT/LR (55%) and LNM (57%) was low. With respect to lymph node staging, the best results were obtained with 18F-DOPA PET. 18F-DOPA PET is a new functional imaging procedure for medullary thyroid carcinoma that seems to provide better results than SRS and 18F-FDG PET. Moreover, the data indicate that no single procedure provides adequate diagnostic certainty. Therefore, 18F-DOPA PET is a useful supplement to morphological diagnostic imaging, improving lymph node staging and enabling a more specific diagnosis of primary tumour and local recurrence.     

Complementary roles of 18F-DOPA PET/CT and 18F-FDG PET/CT in medullary thyroid cancer

Serum calcitonin and carcinoembryonic antigen (CEA) are markers of recurrent or persistent disease in medullary thyroid cancer (MTC). However, conventional imaging often fails to localize metastatic disease. Our aim was to compare fluorine-labeled dihydroxyphenylalanine ((18)F-DOPA) and (18)F-FDG PET/CT with multidetector CT (MDCT) and MRI in recurrent or persistent MTC. METHODS: Nineteen MTC patients with increased calcitonin or CEA on follow-up (mean ± SD, 93 ± 91 mo; range, 4-300 mo) after primary therapy were prospectively imaged with 4 techniques: (18)F-DOPA PET/CT, (18)F-FDG PET/CT, MDCT, and MRI. Images were analyzed for pathologic lesions, which were surgically removed when possible. The correlation between the detection rate for each method and the calcitonin and CEA concentrations and histopathologic findings was investigated. Results: On the basis of histology and follow-up, one or more imaging methods accurately localized metastatic disease in 12 (63%) of 19 patients. The corresponding figures for (18)F-DOPA PET/CT, (18)F-FDG PET/CT, MDCT, and MRI were 11 (58%) of 19, 10 (53%) of 19, 9 (47%) of 19, and 10 (59%) of 17, respectively. Calcitonin and CEA correlated with (18)F-DOPA PET/CT (P = 0.0007 and P = 0.0263, respectively) and (18)F-FDG PET/CT findings (both P < 0.0001). In patients with an unstable calcitonin doubling time (n = 8), (18)F-DOPA and (18)F-FDG PET/CT were equally sensitive. In contrast, for patients with an unstable CEA doubling time (n = 4), (18)F-FDG PET/CT was more accurate. CONCLUSION: For most MTC patients with occult disease, (18)F-DOPA PET/CT accurately detects metastases. In patients with an unstable calcitonin level, (18)F-DOPA PET/CT and (18)F-FDG PET/CT are complementary. For patients with an unstable CEA doubling time, (18)F-FDG PET/CT may be more feasible. MRI is sensitive but has the highest rate of false-positive results.     

18F-dihydroxyphenylalanine PET in patients with biochemical evidence of medullary thyroid cancer: relation to tumor differentiation.

Curative treatment for recurrent medullary thyroid cancer (MTC), diagnosed by rising serum calcitonin, is surgery, but tumor localization is difficult. Therefore, the value of 18F-dihydroxyphenylalanine PET (18F-DOPA PET), 18F-FDG PET, (99m)Tc-V-di-mercaptosulfuricacid (DMSA-V) scintigraphy, and MRI or CT was studied. METHODS: Twenty-one patients with biochemical recurrent or residual MTC underwent 18F-DOPA PET, 18F-FDG PET, DMSA-V scintigraphy, and MRI or CT. Patient- and lesion-based sensitivities were calculated using a composite reference consisting of all imaging modalities. RESULTS: In 76% of all patients with MTC, one or more imaging modalities was positive for MTC lesions. In 6 of 8 patients with a calcitonin level of <500 ng/L, imaging results were negative. In 15 patients with positive imaging results, 18F-DOPA PET detected 13 (sensitivity, 62%; with 4.6 lesions per patient [lpp]). Morphologic imaging (n = 19) was positive in 7 (sensitivity, 37%; 4.7 lpp), DMSA-V (n = 18) in 5 (sensitivity, 28%; 1.1 lpp), and 18F-FDG PET (n = 17) in 4 (sensitivity, 24%; 1.6 lpp). In a lesion-based analysis, 18F-DOPA PET detected 95 of 134 lesions (sensitivity, 71%), morphologic imaging detected 80 of 126 (sensitivity, 64%), DMSA-V detected 20 of 108 (sensitivity, 19%), and 18F-FDG PET detected 48 of 102 (sensitivity, 30%). In 2 of 3 patients with a calcitonin/carcinoembryonic antigen (CEA) doubling time of < or =12 mo, 18F-FDG PET performed better than 18FDOPA PET; in the third patient, 18F-FDG PET was not performed. CONCLUSION: MTC lesions are best detectable when serum calcitonin was >500 ng/L. 18F-DOPA PET is superior to 18F-FDG PET, DMSA-V, and morphologic imaging. With short calcitonin doubling times (< or =12 mo), 18F-FDG PET may be superior.     

Comparison between <Superscript>68</Superscript>Ga-DOTA-NOC and <Superscript>18</Superscript>F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours

PURPOSE: (18)F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that (18)F-DOPA and (68)Ga-DOTA-NOC are more accurate for disease assessment and (68)Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. AIM: The aim of this study was to compare (68)Ga-DOTA-NOC and (18)F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. MATERIALS AND METHODS: Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for (18)F-DOPA and (68)Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). RESULTS: The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. (68)Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while (18)F-DOPA PET was positive in 9/13. On a lesions basis, (68)Ga-DOTA-NOC identified more lesions than (18)F-DOPA (71 vs 45), especially at liver, lung and lymph node level. (68)Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while (18)F-DOPA identified the primary only in two of eight cases. CONCLUSIONS: Although the patients studied are few and heterogeneous, our data show that (68)Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over (18)F-DOPA.     

Molecular imaging of brain tumors with 18F-DOPA PET and PET/CT

The objective of this study was to give an overview of the potential clinical utility of [18F]-L-dihydroxyphenylalanine (18F-DOPA) PET and PET/CT for imaging of brain tumors. Review articles and reference lists were used to supplement the search findings. 18F-DOPA has been investigated as a PET tracer for primary brain tumors, metastases of somatic cancer, and evaluation of relapse of pathology in patients with brain tumor after surgery and/or radiotherapy on the basis of enhanced cell proliferation. Available studies have provided encouraging preliminary results for diagnosis of brain tumors and relapse after surgery/radiotherapy. In the brain, excellent discrimination between tumor and normal tissue can be achieved because of the low physiological uptake of 18F-DOPA and the high ratio between tumor and normal hemispheric tissue. Information on evaluation of brain metastases is limited but encouraging. PET and PET/CT with 18F-DOPA are useful in diagnosing primary brain tumors and should be recommended in the diagnosis of relapse of disease after surgical treatment and/or radiotherapy. Semiquantitative analysis could improve diagnosis while correlative imaging with MRI is essential. Limits are due to low knowledge of potential pitfalls.     

18F-DOPA positron emission tomography for tumour detection in patients with medullary thyroid carcinoma and elevated calcitonin levels

In spite of the availability of numerous procedures, diagnostic imaging of tumour manifestations in patients with medullary thyroid carcinoma and elevated calcitonin levels is often difficult. In the present study, the new procedure of fluorine-18 dihydroxyphenylalanine positron emission tomography (¹⁸F-DOPA PET) was compared with the established functional and morphological imaging methods. After evaluation of the normal distribution of ¹⁸F-DOPA, 11 patients with medullary thyroid carcinoma were examined using ¹⁸F-DOPA PET. Results of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET, somatostatin receptor scintigraphy (SRS) and morphological tomographic imaging (CT/MRI) were available for all patients. All individual procedures were evaluated without reference to prior information. Data assessment for each patient was based on cooperation between experienced radiologists and specialists in nuclear medicine, who considered all the available findings (histological results, imaging, follow-up studies). This cooperation served as the gold standard against which the results of the individual procedures were evaluated. A total of 27 tumours were studied [three primary tumours (PT)/local recurrence (LR), 16 lymph node metastases (LNM) and eight organ metastases (OM)]. ¹⁸F-DOPA PET produced 17 true-positive findings (2 PT/LR, 14 LNM, 1 OM), ¹⁸F-FDG PET 12 (2 PT/LR, 7 LNM, 3 OM), SRS 14 (2 PT/LR, 8 LNM, 4 OM) and morphological imaging 22 (3 PT/LR, 11 LNM, 8 OM). The following sensitivities were calculated with respect to total tumour manifestations: ¹⁸F-DOPA PET 63%, ¹⁸F-FDG PET 44%, SRS 52%, morphological imaging 81%. Thus, the morphological imaging procedures produce the best overall sensitivity, but the specificity for PT/LR (55%) and LNM (57%) was low. With respect to lymph node staging, the best results were obtained with ¹⁸F-DOPA PET. ¹⁸F-DOPA PET is a new functional imaging procedure for medullary thyroid carcinoma that seems to provide better results than SRS and ¹⁸F-FDG PET. Moreover, the data indicate that no single procedure provides adequate diagnostic certainty. Therefore, ¹⁸F-DOPA PET is a useful supplement to morphological diagnostic imaging, improving lymph node staging and enabling a more specific diagnosis of primary tumour and local recurrence.     

Intraindividual comparison of <Superscript>68</Superscript>Ga-DOTA-TATE and <Superscript>18</Superscript>F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours

Aim  To compare the diagnostic impact of ⁶⁸Ga-DOTA-TATE and ¹⁸F-DOPA PET in the diagnosis of well-differentiated metastatic neuroendocrine tumours (NET). Methods  PET/CT using both ⁶⁸Ga-DOTA-TATE and ¹⁸F-DOPA was performed in 25 patients with histologically proven metastatic NET (nine gut, five pancreas, six lung, one paranasal sinus, four with unknown primary). Analyses of PET examinations were patient-based (pathological uptake: yes/no), and based on tumour regions (primary tumour if present and metastases of liver, lung, bones and lymph nodes). The results were compared with the results of contrast enhanced CT, and with plasma serotonin levels, which were available in 24 of the 25 patients. Results  Patient-based sensitivities were 96% for ⁶⁸Ga-DOTA-TATE PET and 56% for ¹⁸F-DOPA PET. ⁶⁸Ga-DOTA-TATE PET delineated metastases in 54 of 55 positive metastatic tumour regions in contrast to 29 of 55 delineated by ¹⁸F-DOPA PET. Overall, ⁶⁸Ga-DOTA-TATE was superior to ¹⁸F-DOPA in 13 patients (two patients showed fewer positive tumour regions with ¹⁸F-DOPA PET). The results were comparable in 12 patients. In 13 of 24 patients, plasma serotonin levels were elevated, and 11 of these 13 patients showed pathological uptake of ¹⁸F-DOPA. Of the 11 patients with normal levels of serotonin, 3 also showed positive ¹⁸F-DOPA uptake. In patients positive for ¹⁸F-DOPA uptake the maximum tumour SUVs were correlated with the levels of serotonin (r=0.66, p=0.01). Conclusion  In this study ⁶⁸Ga-DOTA-TATE PET proved clearly superior to ¹⁸F-DOPA PET for detection and staging of NET. ¹⁸F-DOPA uptake tended to be increased in those patients with elevated plasma serotonin. We conclude that ¹⁸F-DOPA PET should be employed in patients with NET with negative ⁶⁸Ga-DOTA-TATE PET and elevated plasma serotonin.     

Compared to <Superscript>123</Superscript>I-MIBG SPECT/CT, <Superscript>18</Superscript>F-DOPA PET/CT provides accurate tumor extent in patients with extra-adrenal paraganglioma

Aim

The aim of this study was to compare the accuracy of ¹²³I-MIBG SPECT/CT with that of ¹⁸F-DOPA PET/CT for staging extra-adrenal paragangliomas (PGLs) using both functional and anatomical images (i.e., combined cross-sectional imaging) as the reference standards.

Methods

Three men and seven women (age range 26–73 years) with anatomical and/or histologically proven disease were included in this study. Three patients had either metastatic head-and-neck paragangliomas (HNPGLs) or multifocal PGL, and seven patients had nonmetastatic disease. Comparative evaluation included morphological imaging with CT, functional imaging with ¹⁸F-DOPA PET, and ¹²³I-MIBG imaging including SPECT/CT. Imaging results were analyzed on a per-patient and per-lesion basis.

Results

On a per-patient basis, ¹⁸F-DOPA PET’s detection rate for both nonmetastatic and metastatic/multifocal disease was 100%, whereas that of planar ¹²³I-MIBG imaging alone was 10.0% and that of ¹²³I-MIBG SPECT/CT was 20.0%. Overall, on a per-lesion basis, ¹⁸F-DOPA PET showed a sensitivity of 69.2% (McNemar p?<?0.001) compared with anatomical imaging. Sensitivity of planar ¹²³I-MIBG scintigraphy was 5.6%, and that of SPECT/CT was 11.1% (McNemar p?<?0.0001). Overall, ¹⁸F-DOPA PET identified 18 lesions, and anatomical imaging identified 26 lesions; planar ¹²³IMIBG imaging identified only 1 lesion, and SPECT/CT, 2 lesions.

Conclusion

¹⁸F-DOPA PET is more sensitive than is ¹²³I-MIBG imaging, including SPECT/CT, for staging HNPGL. Combined functional and anatomical imaging (PET/CT) is indicated to exclude metastatic disease in extra-adrenal PGL.

     

Comparison of 99mTc-TRODAT-1 SPECT and 18 F-AV-133 PET imaging in healthy controls and Parkinson’s disease patients

^99mTc-TRODAT-1 is the first clinical routine ^99mTc radiopharmaceutical to evaluate dopamine neurons loss in Parkinson's disease (PD). ¹⁸ F-AV-133 is a novel PET radiotracer targeting the vesicular monoamine transporter type 2 (VMAT2) to detect monoaminergic terminal reduction in PD patients. The aim of this study is to compare both images in the same health control (HC) and PD subjects.MethodsEighteen subjects (8 HC and 10 PD) were recruited for ^99mTc-TRODAT-1 SPECT, ¹⁸ F-AV-133 PET and MRI scans within two weeks. The SPECT images were performed at 4-h post-injection for 45 min, and the PET images were performed at 90 min post-injection for 10 min. Each PET and SPECT image was normalized into Montreal Neurological Institute template aided from individual MRI for comparison. For regional analysis, volume of interest (VOIs) of bilateral caudate nuclei, anterior, posterior putamen and occipital cortex (as reference region) were delineated from the normalized MRI. The specific uptake ratio (SUR) was calculated as (regional mean counts/reference mean counts − 1). The nonparametric Mann–Whitney U test was used to evaluate the power of differentiating control from PD subjects for both image modalities. The correlations of the SURs to the clinical parameters were examined. For voxelwise analysis, two-sample t-test for group comparison between HC and PD was computed in both image modalities.ResultsThe SURs of caudate nucleus and putamen correlated well between two image modalities (r = 0.81, p < 0.001), and showed significant different between HC and PD subjects. Of note, the ¹⁸ F-AV-133 SUR displayed a better correlation to PD clinical laterality index as compared to ^99mTc-TRODAT-1 (r = 0.73 vs. r = 0.33). Voxelwise analysis showed more lesions for PD subjects from ¹⁸ F-AV-133 image as compared to ^99mTc-TRODAT-1 especially at the substantia nigra region.Conclusion¹⁸ F-AV-133 PET demonstrated similar performance in differentiation PD from control, and a better correlation to clinical characteristics than that of ^99mTc-TRODAT-1 SPECT. ¹⁸ F-AV-133 PET also showed additional information in substantia nigra integrity in PD subjects by voxelwise analysis. Collectively, ¹⁸ F-AV-133 could be a promising and better tracer for clinical use to detect monoaminergic terminal reduction in PD patients.