68Ga-DOTA-NOC PET/CT in comparison with CT for the detection of bone metastasis in patients with neuroendocrine tumours

Purpose

To retrospectively evaluate the sensitivity, specificity and accuracy of ⁶⁸Ga-DOTA-NOC PET/CT and CT alone for the evaluation of bone metastasis in patients with neuroendocrine tumour (NET).

Methods

From among patients with NET who underwent ⁶⁸Ga-DOTA-NOC PET/CT between April 2006 and November 2008 in our centre, 223 were included in the study. Criteria for inclusion were pathological confirmation of NET and a follow-up period of at least 10 months. PET and CT images were retrospectively reviewed by two nuclear medicine specialists and two radiologists, respectively, without knowledge of the patient history or the findings of other imaging modalities. PET data were compared with the CT findings. Interobserver agreement was evaluated in terms of the kappa score. Clinical and imaging follow-up were used as the standard of reference to evaluate the PET findings.

Results

PET was performed for staging (49/223), unknown primary tumour detection (24/223), restaging (32/223), restaging before radioimmunotherapy (1/223), evaluation during therapy (12/223), equivocal findings on conventional imaging (4/223 at the bone level; 61/223 at sites other than bone), and follow-up (40/223). A very high interobserver agreement was observed. CT detected at least one bone lesion in only 35 of 44 patients with a positive PET scan. In particular, PET showed more lesions in 20/35 patients, a lower number of lesions in 8/35, and the same number in 7/35. The characteristics of the lesions (sclerotic, lytic, mixed) on the basis of the CT report did not influence PET reading. PET revealed the presence of at least one bone metastasis in nine patients with a negative CT scan. Considering patients with a negative PET scan (179), CT showed equivocal findings at the bone level in three (single small sclerotic abnormality in two at the spine level, and bilateral small sclerotic abnormalities in the humeri, femurs and scapula). Clinical follow-up confirmed the PET findings in all patients; thus there were no false-positive or false-negative findings. Considering all patients, PET detected more lesions than CT (246 vs. 194). As compared to CT, on a patient basis PET showed a higher sensitivity (100% vs. 80%), specificity (100% vs. 98%), positive predictive value (100% vs. 92%), and negative predictive value (100% vs. 95%).

Conclusion

In conclusion, ⁶⁸Ga DOTA-NOC PET was more accurate than CT for the identification of bone lesions and led to a change in clinical management in nine patients with a negative CT scan.     

Evaluation of [68Ga]Ga-DATA-TOC for imaging of neuroendocrine tumours: comparison with [68Ga]Ga-DOTA-NOC PET/CT

European Journal of Nuclear Medicine and Molecular Imaging - Recently, the new hybrid chelator DATA (6-amino-1,4-diazepine-triacetate) has been introduced, which has the advantage of high yield and...     

68Ga-DOTA-NOC PET/CT detects somatostatin receptors expression in von hippel-lindau cerebellar disease

A case of Von-Hippel Lindau (VHL) disease has been studied using 68Ga-DOTA-NOC PET/CT. PET/CT demonstrated the presence of somatostatin receptors within 2 focal areas in the cerebellum corresponding to the lesions detected by MRI. Considering the heterogeneous lesions localizations in VHL disease, PET/CT may be a useful imaging modality for diagnosing lesions of central nervous system and neuroendocrine lesions and for direct demonstration of somatostatin receptors for targeted treatment.     

Comparison of 68Ga-DOTATATE and 68Ga-DOTANOC PET/CT imaging in the same patient group with neuroendocrine tumours

Purpose

Recent studies have suggested that positron emission tomography (PET) imaging with ⁶⁸Ga-labelled DOTA-somatostatin analogues (SST) like octreotide and octreotate is useful in diagnosing neuroendocrine tumours (NETs) and has superior value over both CT and planar and single photon emission computed tomography (SPECT) somatostatin receptor scintigraphy (SRS). The aim of the present study was to evaluate the role of ⁶⁸Ga-DOTA-1-NaI³-octreotide (⁶⁸Ga-DOTANOC) in patients with SST receptor-expressing tumours and to compare the results of ⁶⁸Ga-DOTA-D-Phe¹-Tyr³-octreotate (⁶⁸Ga-DOTATATE) in the same patient population.

Methods

Twenty SRS were included in the study. Patients’ age (n?=?20) ranged from 25 to 75?years (mean 55.4?±?12.7?years). There were eight patients with well-differentiated neuroendocrine tumour (WDNET) grade1, eight patients with WDNET grade 2, one patient with poorly differentiated neuroendocrine carcinoma (PDNEC) grade 3 and one patient with mixed adenoneuroendocrine tumour (MANEC). All patients had two consecutive PET studies with ⁶⁸Ga-DOTATATE and ⁶⁸Ga-DOTANOC. All images were evaluated visually and maximum standardized uptake values (SUV_max) were also calculated for quantitative evaluation.

Results

On visual evaluation both tracers produced equally excellent image quality and similar body distribution. The physiological uptake sites of pituitary and salivary glands showed higher uptake in ⁶⁸Ga-DOTATATE images. Liver and spleen uptake values were evaluated as equal. Both ⁶⁸Ga-DOTATATE and ⁶⁸Ga-DOTANOC were negative in 6 (30?%) patients and positive in 14 (70?%) patients. In ⁶⁸Ga-DOTANOC images only 116 of 130 (89?%) lesions could be defined and 14 lesions were missed because of lack of any uptake. SUV_max values of lesions were significantly higher on ⁶⁸Ga-DOTATATE images.

Conclusion

Our study demonstrated that the images obtained by ⁶⁸Ga-DOTATATE and ⁶⁸Ga-DOTANOC have comparable diagnostic accuracy. However, ⁶⁸Ga-DOTATATE seems to have a higher lesion uptake and may have a potential advantage.     

Procedure guidelines for PET/CT tumour imaging with 68Ga-DOTA-conjugated peptides: 68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE

The aim of these guidelines is to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin (SST) receptor PET/CT imaging using ⁶⁸Ga-DOTA-conjugated peptides, analogues of octreotide, that bind to SST receptors. This imaging modality should not be regarded as the only approach to visualizing tumours expressing SST receptors or as excluding other imaging modalities useful for obtaining comparable results. The corresponding guidelines of ¹¹¹In-pentetreotide scintigraphy imaging have been considered and partially integrated with this text. The same has been done with the relevant and recent literature in this field and the final result has been discussed by distinguished experts.     

68Ga-DOTATATE PET/CT in the evaluation of patients with neuroendocrine metastatic carcinoma of unknown origin

Objective

There is little evidence regarding the role of ⁶⁸Ga-DOTATATE PET/CT for the identification of primary tumors in patients with metastatic neuroendocrine carcinoma of unknown primary. The aim of this study is to assess the value of this technique in the mentioned clinical scenario.

Methods

We retrospectively studied twenty-nine patients (mean age 59.5 ± 10.6 years; female 17) with pathologically proven neuroendocrine metastases. In all cases conventional imaging was negative for primary tumor identification. ⁶⁸Ga-DOTATATE PET/CT was performed with a mean dose of 104.2 ± 18.8 MBq, using a 64-slice PET/CT with time-of-flight correction. A team of an experienced radiologist and a nuclear medicine physician evaluated the images. The maximum SUV (SUVm) was measured in all abnormal foci. Histopathology (when available) and/or clinical follow-up with correlative imaging was considered as reference standard.

Results

⁶⁸Ga-DOTATATE PET/CT identified the primary tumor in 17/29 (59 %) patients in the following locations: pancreas (n = 7), ileum (n = 7), duodenum (n = 1), colon (n = 1) and stomach (n = 1). In this population a significant correlation was found between SUVm of primary tumor and metastases (r = 0.815, P < 0.0001). Furthermore, additional sites of unsuspected metastases were demonstrated in 9 patients of this group and in 6 patients in whom no primary tumor was localized, mainly in lymph nodes and mesentery. Pathology confirmation was obtained in 7 patients who underwent surgery, whereas in the remaining 10 patients, correlative imaging and follow-up confirmed primary tumor localization.

Conclusions

⁶⁸Ga-DOTATATE PET/CT is a clinically useful imaging technique for the localization of primary tumors in patients with neuroendocrine metastatic carcinoma of unknown origin with the potential of having a significant impact in patient management and therapy planning.     

Cost comparison of 111In-DTPA-octreotide scintigraphy and 68Ga-DOTATOC PET/CT for staging enteropancreatic neuroendocrine tumours

Purpose  

Although somatostatin receptor positron emission tomography (PET)/CT is gaining increasing popularity and has shown its diagnostic superiority in several studies, ¹¹¹In-diethylenetriaminepentaacetic acid (DTPA)-octreotide is still the current standard for diagnosis of neuroendocrine tumours (NET). The aim of this study was to compare the costs for the two diagnostic tests and the respective consequential costs.     

Somatostatin receptor PET/CT in neuroendocrine tumours: update on systematic review and meta-analysis

Purpose

Neuroendocrine tumours (NET) are uncommon and may be localized in many different places in the body. Traditional imaging has mainly been performed with CT and somatostatin receptor scintigraphy (SRS). Recently, it has become possible to use somatostatin receptor PET/CT (SMSR PET) instead, which might improve diagnostic quality. To evaluate the diagnostic quality of SMSR PET we performed a meta-analysis as an update of a previous study published in 2012.

Methods

A literature search was performed searching MEDLINE, Embase and five other databases with a combination of the expressions “PET”, “positron emission tomography”, “neuroendocrine” and “NET”. The search was updated to 31 December 2012. Studies were selected which evaluated the sensitivity and specificity of SMSR PET for NET in the thorax or abdomen with a study size of at least eight patients. The methodological quality of the included studies was evaluated with QUADAS-2.

Results

Eight studies fulfilled the inclusion criteria and were selected for final analysis, and 14 articles from a previous meta-analysis were added for a total of 22 articles. A total of 2,105 patients were included in the studies, an increase from 567 in the previous meta-analysis. The pooled sensitivity was 93 % (95 % CI 91 – 94 %) and specificity 96 % (95 % CI 95 – 98 %). The area under the summary ROC curve was 0.98 (95 % CI 0.95 – 1.0). In the previous meta-analysis the pooled sensitivity was 93 % (95 % CI 91 – 95 %) and specificity 91 % (95 % CI 82 – 97 %).

Conclusion

SMSR PET has good diagnostic performance for evaluation of NET in the thorax and abdomen, better than SRS which has been the previous standard method. This meta-analysis gives further support for switching to SMSR PET.     

FDG PET/CT in carcinoma of unknown primary

Carcinoma of unknown primary (CUP) is a heterogeneous group of metastatic malignancies in which a primary tumor could not be detected despite thorough diagnostic evaluation. Because of its high sensitivity for the detection of lesions, combined ¹⁸F-fluoro-2-deoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) may be an excellent alternative to CT alone and conventional magnetic resonance imaging in detecting the unknown primary tumor. This article will review the use, diagnostic performance, and utility of FDG PET/CT in CUP and will discuss challenges and future considerations in the diagnostic management of CUP.     

Somatostatin receptor PET in neuroendocrine tumours: 68Ga-DOTA0,Tyr3-octreotide versus 68Ga-DOTA0-lanreotide

Purpose

The aim of this study was to evaluate the impact of ⁶⁸Ga-labelled DOTA⁰-lanreotide (⁶⁸Ga-DOTA-LAN) on the diagnostic assessment of neuroendocrine tumour (NET) patients with low to moderate uptake on planar somatostatin receptor (SSTR) scintigraphy or ⁶⁸Ga-labelled DOTA⁰,Tyr³-octreotide (⁶⁸Ga-DOTA-TOC) positron emission tomography (PET).

Methods

Fifty-three patients with histologically confirmed NET and clinical signs of progressive disease, who had not qualified for peptide receptor radionuclide therapy (PRRT) on planar SSTR scintigraphy or ⁶⁸Ga-DOTA-TOC PET (n?=?38) due to lack of tracer uptake, underwent ⁶⁸Ga-DOTA-LAN PET to evaluate a treatment option with ⁹⁰Y-labelled lanreotide according to the MAURITIUS trial. The included patients received 150?±?30 MBq of each radiopharmaceutical intravenously. PET scans were acquired 60–90 min after intravenous bolus injection. Image results from both PET scans were compared head to head, focusing on the intensity of tracer uptake in terms of treatment decision. CT was used for morphologic correlation of tumour lesions. To further evaluate the binding affinities of each tracer, quantitative and qualitative values were calculated for target lesions.

Results

⁶⁸Ga-DOTA-LAN and ⁶⁸Ga-DOTA-TOC both showed equivalent findings in 24/38 patients when fused PET/CT images were interpreted. The sensitivity, specificity and accuracy of ⁶⁸Ga-DOTA-LAN in comparison to CT were 0.63, 0.5 and 0.62 (n?=?53; p?<?0.0001) and for ⁶⁸Ga-DOTA-TOC in comparison to CT 0.78, 0.5 and 0.76 (n?=?38; p?<?0.013), respectively. ⁶⁸Ga-DOTA-TOC showed a significantly higher maximum standardized uptake value (SUV_max) regarding the primary tumour in 25 patients (p?<?0.003) and regarding the liver in 30 patients (p?<?0.009) compared to ⁶⁸Ga-DOTA-LAN. Corresponding values of both PET scans for tumour and liver did not show any significant correlation. ⁶⁸Ga-DOTA-TOC revealed more tumour sites than ⁶⁸Ga-DOTA-LAN (106 vs 53). The tumour to background ratios for tumour and liver calculated from SUV_max measurements were significantly higher for ⁶⁸Ga-DOTA-TOC than ⁶⁸Ga-DOTA-LAN (p?<?0.02).

Conclusion

⁶⁸Ga-DOTA-TOC PET imaging is an established imaging procedure for accurate staging of NET patients. ⁶⁸Ga-DOTA-LAN should only be considered as a PET tracer of second choice in patients with no pathologic tracer uptake on ⁶⁸Ga-DOTA-TOC PET. In these patients, ⁶⁸Ga-DOTA-LAN PET can provide valuable information when evaluating PRRT as the treatment option, as a broader spectrum of human SSTR subtypes can be detected.     

Use of full-dose contrast-enhanced CT for extrahepatic staging using Gallium-68-DOTATATE PET/CT in patients with neuroendocrine tumors

PURPOSEStudies have demonstrated that positron emission tomography/computed tomography (PET/CT) with Gallium-68 (⁶⁸Ga)-labeled somatostatin analogues are effective at detecting metastatic disease in neuroendocrine tumors (NET), especially extrahepatic metastases. However, PET in combination with full-dose contrast-enhanced CT (ceCT) exposes patients to higher radiation (~25 mSv). The use of non-contrast-enhanced low-dose CT (ldCT) can reduce radiation to about 10 mSv and may avoid contrast-induced side effects. This study seeks to determine whether ceCT could be omitted from NET assessments.METHODSWe retrospectively compared the performance of PET/ldCT versus PET/ceCT in 54 patients (26 male, 28 female) who had undergone a ⁶⁸Ga-DOTATATE PET/CT. The selection criteria were as follows: available ldCT and ceCT, histologically confirmed NET, and follow-up of at least 6 months (median, 12.6 months; range, 6.1–23.2 months). The PET/ldCT and PET/ceCT images were analyzed separately. We reviewed metastases in the lungs, bones, and lymph nodes. The results were compared with the reference standard (clinical follow-up data).RESULTSThe PET/ceCT scans detected 139 true-positive bone lesions compared with 140 lesions detected by the PET/ldCT scans, 106 true-positive lymph node metastases (PET/ceCT) compared with 90 metastases detected by the PET/ldCT scans, and 26 true-positive lung lesions (PET/ceCT) compared with 6 lesions detected by the PET/ldCT scans. The overall lesion-based sensitivity for full-dose PET/ceCT was 97%, specificity 86%, negative predictive value (NPV) 93%, and positive predictive value (PPV) 93%. The overall lesion-based sensitivity for PET/ldCT was 85%, specificity 73%, NPV 72%, and PPV 85%.CONCLUSIONThis study presents the first evidence that ceCT should not be omitted from extrahepatic staging using ⁶⁸Ga-DOTATATE PET/CT in patients with NET. ceCT alone can be used as a follow-up to reduce radiation exposure when the patient has already undergone PET/ceCT and suffers from non-DOTATATE-avid NET.

Previous studies have shown the importance of DOTATOC, DOTATATE, and DOTANOC PET/CT imaging in the diagnosis and accurate staging of neuroendocrine tumors (NET) (1–3). The use of radiolabeled somatostatin analogs in PET/CT has become the standard protocol in NET staging. For many years, octreotide-scintigraphy was used for NET detection and assessment, but this practice has recently been replaced by combined, integrated PET/CT imaging with ⁶⁸Ga-labelled somatostatin analogues. The new method yields higher spatial resolution and facilitates tracer uptake quantification, and ⁶⁸Ga PET/CT has increasingly replaced the use of contrast-enhanced computed tomography (ceCT) alone. ⁶⁸Ga PET/CT provides for precise staging and allows the physician to assess the feasibility of peptide receptor radionuclide therapy (4, 5). There is evidence that PET/ceCT can be beneficial for patients with NET and the ENETS guidelines, among others, recommend PET/ceCT for staging NETs (6–8). However, to date, there is no mandatory consensus on the appropriate ⁶⁸Ga PET/CT protocol for assessing NET. A patient can undergo PET with non-contrast-enhanced low-dose CT (ldCT) or with full-dose ceCT. The diagnostic benefit of surplus ceCT has been assessed particularly for the detection and staging of ¹⁸F-fluorodeoxyglucose (FDG)- avid lymphoma (5) and NET abdominal lesions (9). The benefits of ceCT over PET/ldCT in the detection of extrahepatic metastases have not been analyzed with that kind of detail. As the ceCT method results in substantial radiation exposure (up to 25 mSv), depending on the type of CT machine, any potential dose reduction is desirable. While these levels of exposure are within the limits recommended by Huang et al. (10), they surpass those given by Persson et al. (11). In addition, contrast medium can cause adverse reactions such as hyperthyroidism and renal failure, so it should not be administered without cause, although current ESUR guidelines suggest that contrast media’s adverse effects have been widely overestimated (12). This study addresses whether ceCT is necessary for the detection and assessment of NET extrahepatic metastases and if PET/ldCT is sufficiently reliable.     

Comparison of the prognostic values of 68Ga-DOTANOC PET/CT and 18F-FDG PET/CT in patients with well-differentiated neuroendocrine tumor

Purpose

To determine the prognostic value of ⁶⁸Ga-DOTANOC PET/CT in patients with well-differentiated neuroendocrine tumor (NET), and to compare the prognostic value with that of ¹⁸F-FDG PET/CT and other conventional clinicopathological prognostic factors.

Methods

Data from 37 consecutive patients (age 46.6?±?13.5 years, 51 % men) with well-differentiated NET who underwent ⁶⁸Ga-DOTANOC PET/CT and ¹⁸F-FDG PET/CT were analyzed. All patients underwent a baseline visit with laboratory and radiological examinations. Clinical and imaging follow-up was performed in all patients. Progression-free survival (PFS) was measured from the date of the first PET/CT scan to the first documentation of progression of disease.

Results

⁶⁸Ga-DOTANOC PET/CT was positive in 37 of the 37 patients and ¹⁸F-FDG PET/CT was positive in 21. During follow-up 10 patients (27 %) showed progression of disease and 27 (73 %) showed no progression (24 stable disease, 3 partial response). The median follow-up was 25 months (range 2 – 52 months). Among the variables evaluated none was significantly different between the progressive disease and nonprogressive disease groups, with only SUVmax on ⁶⁸Ga-DOTANOC PET/CT being borderline significant (P?=?0.073). In the univariate analysis for PFS outcome, SUVmax on ⁶⁸Ga-DOTANOC PET/CT (HR 0.122, 95 % CI 0.019 – 0.779; P?=?0.026) and histopathological tumor grade (HR 4.238, 95 % CI 1.058 – 16.976; P?=?0.041) were found to be associated with PFS. Other factors including age, sex, primary site, Ki-67 index, TNM stage, ¹⁸F-FDG PET/CT status (positive/negative), SUVmax on ¹⁸F-FDG PET/CT and type of treatment were not significant. In multivariable analysis, only SUVmax on ⁶⁸Ga-DOTANOC PET/CT was found to be an independent positive predictor of PFS (HR 0.122, 95 % CI 0.019 – 0.779; P?=?0.026).

Conclusion

SUVmax measured on ⁶⁸Ga-DOTANOC PET/CT is an independent, positive prognostic factor in patients with well-differentiated NET and is superior to SUVmax on ¹⁸F-FDG PET/CT and conventional clinicopathological factors for predicting PFS.     

原发性骨肌肿瘤的PET/CT应用进展

PET/CT的融合成像对众多实性肿瘤的分期及治疗有重要价值。然而,该技术对骨肌恶性肿瘤的评估尚未实现常规临床应用。采用MR和CT的体层成像技术进行评估     

PET/CT in primary musculoskeletal tumours: a step forward

Hybrid imaging with combined positron emission tomography/computed tomography (PET/CT) plays an important role in the staging and management of a wide variety of solid tumours. However, its use in the evaluation of musculoskeletal malignancy has not yet entered routine clinical practice. Cross-sectional imaging with magnetic resonance imaging (MR) and computed tomography have well-established roles but there is increasing evidence for the selective use of PET/CT in the management of these patients. The aims of this article are to review the current evidence and clinical applications of PET/CT in primary musculoskeletal tumours and discuss potential future developments using novel PET tracers and integrated PET/MR.     

PET and PET/CT in endocrine tumours

Functional information provided by PET tracers together with the superior image quality and the better data quantification by PET technology had a changing effect on the significance of nuclear medicine in medical issues. Recently introduced hybrid PET/CT systems together with the introduction of novel PET radiopharmaceuticals have contributed to the fact that nuclear medicine has become a growing diagnostic impact on endocrinology. In this review imaging strategies, different radiopharmaceuticals including the basic mechanism of their cell uptake, and the diagnostic value of PET and PET/CT in endocrine tumours except differentiated thyroid carcinomas will be discussed.     

18F-FDG PET/CT在不明原发灶肿瘤中的临床应用价值

目的探讨18F-FDG PET/CT全身显像在不明原发灶肿瘤（CUP）诊断中的临床应用价值。方法回顾分析46例于2015年2月至2016年6月在我院行常规检查未能发现肿瘤原发灶而进一步行18F-FDG PET/CT全身显像查找肿瘤原发灶的转移性肿瘤患者的资料。PET/CT图像分析采用视觉及半定量分析方法。通过病理活检和（或）临床综合诊断、临床随访对结果进行评价。结果46例患者中,18F-FDG PET/CT显像找到原发肿瘤33例,均经过病理活检及临床随访证实;13例未发现原发病灶。18F-FDG PET/CT对不明肿瘤原发灶的检出率为71.7%（33/46）,其中阳性患者中淋巴瘤3例、胃癌2例、食管癌4例、卵巢癌3例、肺癌14例、肝癌2例、尿路上皮癌1例、鼻咽癌2例、多发性骨髓瘤1例、降结肠癌1例。转移方式主要有淋巴结转移32例、骨转移20例、肝转移13例、肺转移9例、胸膜腹膜转移5例、肾上腺转移3例、脑转移4例、皮下转移3例、心包膜转移1例。结论18F-FDG PET/CT全身显像对CUP的检出率显著优于一般常规检查,对临床指导治疗有着重要意义。