Diagnostic value of combining <Superscript>11</Superscript>C-choline and <Superscript>18</Superscript>F-FDG PET/CT in hepatocellular carcinoma

Purpose

In this prospective study, our goal was to emphasize the diagnostic value of combining ¹¹C-choline and ¹⁸F-FDG PET/CT for hepatocellular carcinoma (HCC) in patients with chronic liver disease.

Methods

Thirty-three consecutive patients were enrolled. All patients were suspected to have HCC based on CT and/or MRI imaging. A final diagnosis was obtained by histopathological examination or by imaging alone according to American Association for the Study of Liver Disease criteria. All patients underwent PET/CT with both tracers within a median of 5 days. All lesions showing higher tracer uptake than normal liver were considered positive for HCC. We examined how tracer uptake was related to biological (serum α-fetoprotein levels) and pathological (differentiation status, peritumoral capsule and vascular invasion) prognostic markers of HCC, as well as clinical observations at 6 months (recurrence and death).

Results

Twenty-eight HCC, four cholangiocarcinomas and one adenoma were diagnosed. In the HCC patients, the sensitivity of ¹¹C-choline, ¹⁸F-FDG and combined ¹¹C-choline and ¹⁸F-FDG PET/CT for the detection of HCC was 75 %, 36 % and 93 %, respectively. Serum α-fetoprotein levels >200 ng/ml were more frequent among patients with ¹⁸F-FDG-positive lesions than those with ¹⁸F-FDG-negative lesions (p?<?0.05). Early recurrence (n=2) or early death (n=5) occurred more frequently in patients with ¹⁸F-FDG-positive lesions than in those with ¹⁸F-FDG-negative lesions (p?<?0.05).

Conclusion

The combined use of ¹¹C-choline and ¹⁸F-FDG PET/CT detected HCC with high sensitivity. This approach appears to be of potential prognostic value and may facilitate the selection of patients for surgical resection or liver transplantation.

     

Evaluation of <Superscript>68</Superscript>Ga-DOTA-TOC PET/CT for the detection of duodenopancreatic neuroendocrine tumors in patients with MEN1

Context

Somatostatin receptor scintigraphy with ¹¹¹In-pentetreotide (SRS) is used to detect duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). However, SRS has limited sensitivity for this purpose. Positron emission tomography/computed tomography (PET/CT) with ⁶⁸Ga-DOTA-TOC has a higher rate of sporadic dpNETs detection than SRS but there is little data for dpNETs detection in MEN1.

Purpose

To compare the performances of ⁶⁸Ga-DOTA-TOC PET/CT, SRS and contrast-enhanced computed tomography (CE-CT) to diagnose dpNETs in MEN1.

Design and setting

Single-institution prospective comparative study

Patients and methods

Nineteen consecutive MEN1 patients (aged 47?±?13 years) underwent ⁶⁸Ga-DOTA-TOC PET/CT, SRS, and CE-CT within 2 months in random order. Blinded readings of images were performed separately by experienced physicians. Unblinded analysis of CE-CT, combined with additional magnetic resonance imaging, endoscopic-ultrasound, ¹⁸F-2-fluoro-deoxy-d-glucose (¹⁸F-FDG) PET/CT or histopathology results served as reference standard for dpNETs diagnosis.

Results

The sensitivity of ⁶⁸Ga-DOTA-TOC PET/CT, SRS, and CE-CT was 76, 20, and 60 %, respectively (p?<?0.0001). All the true-positive lesions detected by SRS were also depicted on ⁶⁸Ga-DOTA-TOC PET/CT. ⁶⁸Ga-DOTA-TOC PET/CT detected lesions of smaller size than SRS (10.7?±?7.6 and 15.2?±?5.9 mm, respectively, p?<?0.03). False negatives of ⁶⁸Ga-DOTA-TOC PET/CT included small dpNETs (<10 mm) and ¹⁸F-FDG PET/CT positive aggressive dpNETs. No false positives were recorded. In addition, whole-body mapping with ⁶⁸Ga-DOTA-TOC PET/CT identified extra-abdominal MEN1-related tumors including one neuroendocrine thymic carcinoma identified by the three imaging procedures, one bronchial carcinoid undetected by CE-CT and three meningiomas undetected by SRS.

Conclusions

Owing to higher diagnostic performance, ⁶⁸Ga-DOTA-TOC PET/CT (or alternative ⁶⁸Ga-labeled somatostatin analogues) should replace ¹¹¹In-pentetreotide in the investigation of MEN1 patients.

     

Diagnostic performance and impact on patient management of <Superscript>68</Superscript>Ga-DOTA-TOC PET/CT for detecting osteomalacia-associated tumours

Purpose

Oncogenic osteomalacia is an endocrine disorder induced by small benign tumours (TIO) producing excessive fibroblast growth factor-23 (FGF23). The only way of curing oncogenic osteomalacia is surgical resection of the culprit TIO, which is extremely difficult to detect using conventional imaging modalities due to its small size and variable location in the body. Since TIO frequently overexpress somatostatin receptors, a clinical utility of SPECT or PET with radiolabelled somatostatin analogues has been reported. Among them, ⁶⁸Ga-DOTA-TOC has recently been granted a marketing authorization, facilitating its routine application. We report here the results of the first series evaluating the diagnostic performance of ⁶⁸Ga-DOTA-TOC PET/CT in detecting TIO and its impact on patient management.

Methods

⁶⁸Ga-DOTA-TOC PET/CT and clinical and imaging data from 15 patients with clinical and biochemical signs of oncogenic osteomalacia were retrospectively reviewed. The ⁶⁸Ga-DOTA-TOC PET/CT findings were compared with the results of post-surgical pathology and clinical and biochemical follow-up.

Results

⁶⁸Ga-DOTA-TOC PET/CT resulted in the detection of one focus suspicious for TIO in nine of 15 patients (60%), and a tumour was surgically removed in eight. Post-operative pathology confirmed a TIO in those eight patients whose symptoms diminished promptly and biochemical anomalies resolved. ⁶⁸Ga-DOTA-TOC PET/CT sensitivity, specificity and accuracy were 73%, 67% and 71%, respectively. ⁶⁸Ga-DOTA-TOC PET/CT findings affected patient management in 67% of cases. In particular, ⁶⁸Ga-DOTA-TOC PET/CT was able to detect the TIO with a negative or a false-positive result of a previous ¹¹¹In-pentetreotide SPECT/CT in 5/8 patients (63%) or a previous FDG PET/CT in 7/11 patients (64%). No close relationship was found between the positivity of ⁶⁸Ga-DOTA-TOC PET/CT and the serum level of a biochemical marker. However, a true-positive result of ⁶⁸Ga-DOTA-TOC PET/CT was obtained in only one patient with a non-elevated serum level of FGF23.

Conclusion

⁶⁸Ga-DOTA-TOC PET/CT is an accurate imaging modality in the detection of TIO; in particular, it is worthwhile after failure of somatostatin receptor SPECT(/CT) or FDG PET/CT.

     

Treatment response evaluation with <Superscript>18</Superscript>F-FDG PET/CT and <Superscript>18</Superscript>F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation

Aim

The aim of this study was to assess the combined use of the radiotracers ¹⁸F-FDG and ¹⁸F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT).

Patients and methods

Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with ¹⁸F-FDG and ¹⁸F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD).

Results

An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, ¹⁸F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, ¹⁸F-FDG PET/CT-based treatment response revealed CR in 14 patients (¹⁸F-FDG PET/CT CR), PR in 11 patients (¹⁸F-FDG PET/CT PR) and progressive disease in four patients (¹⁸F-FDG PET/CT PD). In terms of ¹⁸F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, ¹⁸F-NaF PET/CT depicted 56 of the 129 ¹⁸F-FDG positive lesions (43 %). Follow-up ¹⁸F-NaF PET/CT showed persistence of 81.5 % of the baseline ¹⁸F-NaF positive MM lesions after treatment, despite the fact that 64.7 % of them had turned to ¹⁸F-FDG negative. Treatment response according to ¹⁸F-NaF PET/CT revealed CR in one patient (¹⁸F-NaF PET/CT CR), PR in five patients (¹⁸F-NaF PET/CT PR), SD in 12 patients (¹⁸F-NaF PET/CT SD), and PD in seven patients (¹⁸F-NaF PET/CT PD). Dynamic ¹⁸F-FDG and ¹⁸F-NaF PET/CT studies showed that SUV_average, SUV_max, as well as the kinetic parameters K₁, influx and FD from reference bone marrow and skeleton responded to therapy with a significant decrease (p?<?0.001).

Conclusion

F-FDG PET/CT demonstrated a sensitivity of 57.7 % and a specificity of 100 % in treatment response evaluation of MM. Despite its limited sensitivity, the performance of ¹⁸F-FDG PET/CT was satisfactory, given that 6/9 false negative patients in follow-up scans (66.7 %) were clinically characterized as nCR, a disease stage with very low tumor mass. On the other hand, ¹⁸F-NaF PET/CT does not seem to add significantly to ¹⁸F-FDG PET/CT in treatment response evaluation of MM patients undergoing HDT and ASCT, at least shortly after therapy.

     

Role of <Superscript>18</Superscript>F-FDG PET/CT in patients affected by Langerhans cell histiocytosis

Purpose

Langerhans cell histiocytosis (LCH) is a rare hematological disorder for which the utility of¹⁸F-FDG PET/CT is unclear. Our aim was to explore the metabolic features of LCH and the possible role of¹⁸F-FDG PET/CT in LCH evaluation.

Materials and methods

We found 17 patients with histologically proven LCH who underwent 17¹⁸F-FDG PET/CT scans for staging and 42 scans for restaging/follow-up purposes. PET/CT results were compared with those obtained from other conventional imaging modalities (bone scintigraphy, plain radiogram, computed tomography, magnetic resonance).

Results

¹⁸F-FDG PET/CT was positive in 15/17 patients, and it detected 36/37 lesions; all bone and extraskeletal lesions, except for a cecal lesion, were¹⁸F-FDG-avid. Only 1/4 of the patients with lung LCH had hypermetabolic lesions. The average SUV_max of the FDG-avid lesions was 7.3 ± 6.7, the average lesion-to-liver SUV_max ratio was 3.4 ± 2.5, and the average lesion-to-blood pool SUV_max ratio was 4 ± 3.2. In comparison to other imaging methods,¹⁸F-FDG PET/CT detected additional lesions or was able to evaluate treatment response earlier in 33/74 cases; it was confirmatory in 38/74 and detected fewer lesions in 3/74 (all three with lung LCH).

Conclusions

¹⁸F-FDG PET/CT seems to be useful for evaluating LCH when compared to conventional imaging, except in pulmonary cases. It can be used both for staging and restaging purposes.

     

Prognostic implications of <Superscript>62</Superscript>Cu-diacetyl-bis (<Emphasis Type="Italic">N</Emphasis><Superscript>4</Superscript>-methylthiosemicarbazone) PET/CT in patients with glioma

Objective

The potential of positron emission tomography/computed tomography using ⁶²Cu-diacetyl-bis (N⁴-methylthiosemicarbazone) (⁶²Cu-ATSM PET/CT), which was originally developed as a hypoxic tracer, to predict therapeutic resistance and prognosis has been reported in various cancers. Our purpose was to investigate prognostic value of ⁶²Cu-ATSM PET/CT in patients with glioma, compared to PET/CT using 2-deoxy-2-[¹⁸F]fluoro-d-glucose (¹⁸F-FDG).

Method

56 patients with glioma of World Health Organization grade 2–4 were enrolled. All participants had undergone both ⁶²Cu-ATSM PET/CT and ¹⁸F-FDG PET/CT within mean 33.5 days prior to treatment. Maximum standardized uptake value and tumor/background ratio were calculated within areas of increased radiotracer uptake. The prognostic significance for progression-free survival and overall survival were assessed by log-rank test and Cox’s proportional hazards model.

Results

Disease progression and death were confirmed in 37 and 27 patients in follow-up periods, respectively. In univariate analysis, there was significant difference of both progression-free survival and overall survival in age, tumor grade, history of chemoradiotherapy, maximum standardized uptake value and tumor/background ratio calculated using ⁶²Cu-ATSM PET/CT. Multivariate analysis revealed that maximum standardized uptake value calculated using ⁶²Cu-ATSM PET/CT was an independent predictor of both progression-free survival and overall survival (p?<?0.05). In a subgroup analysis including patients of grade 4 glioma, only the maximum standardized uptake values calculated using ⁶²Cu-ATSM PET/CT showed significant difference of progression-free survival (p?<?0.05).

Conclusions

⁶²Cu-ATSM PET/CT is a more promising imaging method to predict prognosis of patients with glioma compared to ¹⁸F-FDG PET/CT.

     

Different predictive values of interim <Superscript>18</Superscript>F-FDG PET/CT in germinal center like and non-germinal center like diffuse large B-cell lymphoma

Purpose

Diffuse large B-cell lymphoma (DLBCL) is a pathologically heterogeneous disease with different prognoses according to its molecular profiles. Despite the broad usage of ¹⁸F-fluoro-2-dexoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT), previous studies that have investigated the value of interim ¹⁸F-FDG PET/CT in DLBCL have given the controversial results. The purpose of this study was to evaluate the prognostic value of interim ¹⁸F-FDG PET/CT in DLBCL according to germinal center B cell-like (GCB) and non-GCB molecular profiling.

Methods

We enrolled 118 newly diagnosed DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Interim ¹⁸F-FDG PET/CT scans performed after 2 or 3 cycles of R-CHOP treatment were evaluated based on the Lugano response criteria. Patients were grouped as GCB or non-GCB molecular subtypes according to immunohistochemistry results of CD10, BCL6, and MUM1, based on Hans’ algorithm.

Results

In total 118 DLBCL patients, 35 % were classified as GCB, and 65 % were classified as non-GCB. Interim PET/CT was negative in 70 %, and positive in 30 %. During the median follow-up period of 23 months, the positive interim ¹⁸F-FDG PET/CT group showed significantly inferior progression free survival (PFS) compared to the negative interim ¹⁸F-FDG PET/CT group (P = 0.0004) in entire patients. A subgroup analysis according to molecular profiling demonstrated significant difference of PFS between the positive and negative interim ¹⁸F-FDG PET groups in GCB subtype of DLBCL (P = 0.0001), but there was no significant difference of PFS between the positive and negative interim ¹⁸F-FDG PET groups in non-GCB subtype of DLBCL.

Conclusions

Interim ¹⁸F-FDG PET/CT scanning had a significant predictive value for disease progression in patients with the GCB subtype of DLBCL treated with R-CHOP, but not in those with the non-GCB subtype. Therefore, molecular profiles of DLBCL should be considered for interim ¹⁸F-FDG PET/CT practice.

     

Influence of <Superscript>18</Superscript>F-FDG PET/CT on therapy management in patients with stage III/IV malignant melanoma

Purpose

To evaluate the influence of ¹⁸F-FDG PET/CT in comparison to CT alone on treatment decisions in patients with advanced melanoma and to analyse the 5-year survival data in comparison to literature data.

Methods

Therapy management in 64 consecutive patients (primary staging n?=?52; surveillance n?=?12) with stage III/IV melanoma who underwent ¹⁸F-FDG PET/CT between 2004 and 2005 in our department was retrospectively analysed. Treatment decisions were made by two dermatooncologists for each patient twice, first based on the CT results and then based on the PET/CT results. Therapy changes based on the PET/CT results were classified as “major” (e.g. change from metastasectomy to systemic therapy) or “minor” (e.g. change from first to second line chemotherapy). The 5-year survival data of different patient cohorts were calculated.

Results

In the 52 patients in the primary staging group, the results of ¹⁸F-FDG PET/CT led to therapy change in 59 % and a major therapy change in 52 %. ¹⁸F-FDG PET/CT led to the avoidance of futile operations in 13 patients with suspicious lesions on CT that were deemed nontumorous on PET/CT. In the 12 patients in the surveillance group, the results of ¹⁸F-FDG PET/CT led to therapy change in 33 % and a major change in 17 %. The 5-year survival rates were 30 % in the entire cohort, 34 % in the primary staging group, and 17 % in the surveillance group. A significant overall survival benefit was observed in patients in whom ¹⁸F-FDG PET/CT excluded metastases or in whom metastases could be completely removed compared with patients who were not eligible for surgery (41 % vs. 10 %).

Conclusion

Primary staging of patients with stage III/IV melanoma should be performed with ¹⁸F-FDG PET/CT, leading to higher diagnostic accuracy and enabling individualized therapeutic management, especially optimal patient selection for metastasectomy. This strategy may extend long-term survival even in patients with advanced disease.

     

Incidental focal <Superscript>18</Superscript>F-FDG uptake in the frontal process of the maxilla on PET/CT: prevalence and clinical significance

Objective

We investigated the prevalence and clinical significance of incidental focal ¹⁸F-FDG uptake in the frontal process of the maxilla, mimicking malignancy on PET/CT.

Methods

From a total of 32,834 patients who underwent ¹⁸F-FDG PET/CT, patients with focal uptake in the frontal process of the maxilla were selected by a database search. For those patients, medical records including relevant imaging studies were reviewed.

Results

Thirty-nine patients (0.12 %) demonstrated focal uptake on PET/CT. On CT of PET/CT, all lesions showed ground-glass attenuation with or without bony expansion, consistent with fibrous dysplasia. When comparing previous PET/CT, follow-up PET/CT, and CT, a significant difference in degree of ¹⁸F-FDG uptake was noted, with no associated change in the size of maxillary lesions. There were no patients who had symptoms or signs related to maxillary lesions during follow-up.

Conclusion

Focal ¹⁸F-FDG uptake in the frontal process of the maxilla is a rare, incidental, and persistent finding with variable uptake and can represent a benign condition.

     

PET/CT comparing <Superscript>68</Superscript>Ga-DOTATATE and other radiopharmaceuticals and in comparison with CT/MRI for the localization of sporadic metastatic pheochromocytoma and paraganglioma

Purpose

Pheochromocytomas/paragangliomas (PPGLs) and their metastases are tumors that predominantly express somatostatin receptor 2 (SSR2). ⁶⁸Ga-DOTA(0)-Tyr(3)-octreotate (⁶⁸Ga-DOTATATE) is a PET radiopharmaceutical with both high and selective affinity for SSRs. The purpose of this study was to evaluate the utility of ⁶⁸Ga-DOTATATE in comparison with other specific and nonspecific radiopharmaceuticals recommended in the current guidelines for the localization of metastatic sporadic PPGL by PET/CT.

Methods

This prospective study included 22 patients (15 men, 7 women; aged 50.0?±?13.9 years) with confirmed metastatic PPGL, a negative family history for PPGL, and negative genetic testing, who underwent ⁶⁸Ga-DOTATATE, ¹⁸F-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) PET/CT, and CT/MRI. Only 12 patients underwent an additional ¹⁸F-fluorodihydroxyphenylalanine (¹⁸F-FDOPA) PET/CT scan and only 11 patients underwent an additional ¹⁸F-fluorodopamine (¹⁸F-FDA) PET/CT scan. The rates of detection of metastatic lesions were compared among all the imaging studies. A composite of all functional and anatomical imaging studies served as the imaging comparator.

Results

⁶⁸Ga-DOTATATE PET/CT showed a lesion-based detection rate of 97.6 % (95 % confidence interval, CI, 95.8 – 98.7 %). ¹⁸F-FDG PET/CT, ¹⁸F-FDOPA PET/CT, ¹⁸F-FDA PET/CT, and CT/MRI showed detection rates of 49.2 % (CI 44.5 – 53.6 %; p?<?0.01), 74.8 % (CI 69.0 – 79.9 %); p?<?0.01), 77.7 % (CI 71.5 – 82.8 %; p?<?0.01), and 81.6 % (CI 77.8 – 84.8 %; p?<?0.01), respectively.

Conclusion

The results of this study demonstrate the superiority of ⁶⁸Ga-DOTATATE PET/CT in the localization of sporadic metastatic PPGLs compared to all other functional and anatomical imaging modalities, and suggest modification of future guidelines towards this new imaging modality.

     

<Superscript>18</Superscript>F-FDG and <Superscript>18</Superscript>F-FLT PET/CT imaging in the characterization of mediastinal lymph nodes

Purpose

There is currently no single modality for accurate characterization of enlarged mediastinal lymph nodes into benign or malignant. Recently ¹⁸F-fluorothymidine (FLT) has been used as a proliferation marker. In this prospective study, we examined the role of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) and ¹⁸F-FLT PET/CT in categorizing mediastinal lymph nodes as benign or malignant.

Materials and methods

A total of 70 consecutive patients with mediastinal lymphadenopathy detected on computed tomography (CT) or chest radiograph underwent whole body ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT (within 1 week of each other). Lymph nodal tracer uptake was determined by calculation of standardized uptake value (SUV) with both the tracers. Results of PET/CT were compared with histopathology of the lymph nodes.

Results

Histopathology results showed thirty-seven patients with sarcoidosis, seven patients with tuberculosis, nine patients with non-small cell lung cancer, five patients with Hodgkin’s lymphoma and twelve patients with non-Hodgkin’s lymphoma. The mean FDG SUV_max of sarcoidosis, tuberculosis, Hodgkin’s and non-Hodgkin’s lymphoma was 12.7, 13.4, 8.2, and 8.8, respectively, and the mean FLT SUV_max was 6.0, 5.4, 4.4, and 3.8, respectively. It was not possible to characterize mediastinal lymphadenopathy as benign or malignant solely based on FDG SUV_max values (p > 0.05) or FLT SUV_max values (p > 0.05). There was no significant difference in FDG uptake (p > 0.9) or FLT uptake (p > 0.9) between sarcoidosis and tuberculosis. In lung cancer patients, the FDG SUV_max and FLT SUV_max of those lymph nodes with tumor infiltration on biopsy was 6.7 and 3.9, respectively, and those without nodal infiltration was 6.4 and 3.7, respectively, and both the tracers were not able to characterize the nodal status as malignant or benign (p > 0.05).

Conclusion

Though ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT reflect different aspects of biology, i.e., proliferation and metabolism, respectively, neither tracer could provide satisfactory categorization of benign and malignant lymph nodes. The results of this study clearly suggest that differentiation of mediastinal nodes into benign and malignant solely based on SUV_max values cannot be relied upon, especially in settings where tuberculosis and sarcoidosis are common.

     

Outcome and toxicity of salvage therapy with <Superscript>177</Superscript>Lu-octreotate in patients with metastatic gastroenteropancreatic neuroendocrine tumours

Purpose

We assessed the outcome and toxicity of salvage therapy (repeat treatment) with ¹⁷⁷Lu-octreotate and high cumulative activities in patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP-NET).

Methods

We retrospectively analysed a consecutive cohort of 33 patients with metastatic GEP-NET who underwent salvage peptide receptor radionuclide therapy (PRRT) in our institution. All patients had progressive NET prior to salvage treatment and had shown an initial response to PRRT. The mean cumulative activity was 44.3 GBq (30.0–83.7 GBq). Radiographic response was assessed using CT and/or MRI according to modified SWOG criteria. Toxicity was evaluated using laboratory data, including complete blood counts and renal function tests using CTCAE 3.0. Survival analysis was performed with the Kaplan-Meier curve method and a significance level at p?<?0.05.

Results

Radiographic responses consisted of complete response in 1 patient (3.0 %), partial response in 6 patients (18.2 %), minor response in 1 patient (3.0 %), stable disease in 14 patients (42.4 %), and progressive disease in 11 patients (33.3 %). Median progression-free survival (PFS) from the start of salvage therapy was 13 months (95 % CI 9–18) and patients with a history of a durable PFS after initial PRRT tended to have long-lasting PFS after salvage treatment (p?=?0.04). None of the patients developed severe nephrotoxicity (grade 3/4) or a myelodysplastic syndrome during follow-up. Relevant albeit reversible haematotoxicity (grade 3/4) occurred in 7 patients (21.2 %). The cumulative administered activity was not associated with an increased incidence of haematotoxicity.

Conclusion

PRRT with ¹⁷⁷Lu-octreotate in the re-treatment setting is safe and effective in patients with metastatic GEP-NET.

     

68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT

Purpose

We wanted to establish the range of ⁶⁸Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT).

Methods

In 249 patients, 390 ⁶⁸Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies).

Results

SUV_max (mean ± standard deviation) values of ⁶⁸Ga-DOTA-TOC were 29.8?±?16.5 in 162 liver metastases, 19.8?±?18.8 in 89 bone metastases and 34.6?±?17.1 in 43 pancreatic NET (33.6?±?14.3 in 30 tumours of the uncinate process and 36.3?±?21.5 in 13 tumours of the pancreatic tail). A significant difference in SUV_max (p?<?0.02) was found in liver metastases of NET patients treated with PRRT. There were significant differences in SUV_max between nonmalignant and malignant tissue for both bone and liver metastases and for pancreatic NET including the uncinate process (p?<?0.0001). At a cut-off value of 17.1 the specificity and sensitivity of SUV_max for differentiating tumours in the uncinate process were 93.6 % and 90.0 %, respectively (p?<?0.0001).

Conclusion

⁶⁸Ga-DOTA-TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUV_max can offer important clinical information to distinguish between physiological and pathological somatostatin receptor expression, especially in the uncinate process. PRRT does not significantly influence SUV_max, except in liver metastases of patients with NET.     

Evaluation of <Superscript>68</Superscript>Ga-DOTATOC PET/MRI for whole-body staging of neuroendocrine tumours in comparison with <Superscript>68</Superscript>Ga-DOTATOC PET/CT

Objectives

To compare the diagnostic performance of ⁶⁸Ga-DOTATOC PET/MRI and ⁶⁸Ga-DOTATOC PET/CT in the whole-body staging of patients with neuroendocrine tumours (NET).

Methods

Thirty patients with histopathologically confirmed NET underwent PET/CT and PET/MRI in a single-injection protocol. PET/CT and PET/MRI scans were prospectively evaluated with regard to lesion count, localization, nature (NET/non-NET), and conspicuity (four-point scale). Histopathology and follow-up imaging served as the reference standards. The proportions of NET and non-NET lesions rated correctly were compared using McNemar’s chi-squared test. The Wilcoxon test was used to assess differences in SUVmax and lesion conspicuity. The correlation between the SUVmax for the same lesions from each modality was analysed using Pearson’s correlation coefficient (r).

Results

According to the reference standard, there were 197 lesions (142 NET, 55 non-NET). Lesion-based analysis showed a higher proportion of correctly rated NET lesions on PET/MRI than on PET/CT (90.8% vs. 86.7%, p?=?0.031), whereas on PET/CT there was a higher proportion of correctly rated non-NET lesions (94.5% vs. 83.6%, p?=?0.031). SUVmax was strongly correlated (r?=?0.86; p?<?0.001) and did not differ significantly (p?=?0.35) between the modalities. Overall conspicuity and NET lesion conspicuity were higher on PET/MRI (both p?<?0.01).

Conclusions

Ga-DOTATOC PET/MRI yielded a higher proportion of correctly rated NET lesions and should be regarded as a valuable alternative to ⁶⁸Ga-DOTATOC PET/CT in whole-body staging of NET patients.

Key Points

? ⁶⁸ Ga-DOTATOC PET/MRI correctly identified more NET lesions than ⁶⁸ Ga-DOTATOC PET/CT. ? ⁶⁸ Ga-DOTATOC PET/MRI provides better NET lesion conspicuity than ⁶⁸ Ga-DOTATOC PET/CT. ? SUVmax values from the two modalities are strongly correlated and do not differ significantly.

     

Assessing the role of <Superscript>18</Superscript>F-FDG PET and <Superscript>18</Superscript>F-FDG PET/CT in the diagnosis of soft tissue musculoskeletal malignancies: a systematic review and meta-analysis

Purpose

Twelve years ago a meta-analysis evaluated the diagnostic performance of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in assessing musculoskeletal soft tissue lesions (MsSTL). Currently, PET/CT has substituted PET imaging; however, there has not been any published meta-analysis on the use of PET/CT or a comparison of PET/CT with PET in the diagnosis of MsSTL. Therefore, we conducted a meta-analysis to identify the current diagnostic performance of ¹⁸F-FDG PET/CT and determine if there is added value when compared to PET.

Methods

A systematic review of English articles was conducted, and MEDLINE PubMed, the Cochrane Library, and Embase were searched from 1996 to March 2015. Studies exploring the diagnostic accuracy of ¹⁸F-FDG PET/CT (or dedicated PET) compared to histopathology in patients with MsSTL undergoing investigation for malignancy were included.

Results

Our meta-analysis included 14 articles composed of 755 patients with 757 soft tissue lesions. There were 451 (60 %) malignant tumors and 306 benign lesions. The ¹⁸F-FDG PET/CT (and dedicated PET) mean sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for diagnosing MsSTL were 0.96 (0.90, 1.00), 0.77 (0.67, 0.86), 0.88 (0.85, 0.91), 0.86 (0.78, 0.94), and 0.91 (0.83, 0.99), respectively. The posterior mean (95 % highest posterior density interval) for the AUC was 0.92 (0.88, 0.96). PET/CT had higher specificity, accuracy, and positive predictive value when compared to a dedicated PET (0.85, 0.89, and 0.91 vs 0.71, 0.85, and 0.82, respectively).

Conclusion

¹⁸F-FDG PET/CT and dedicated PET are both highly accurate in the diagnosis of MsSTL. PET/CT is more accurate and specific and has a higher positive predictive value than PET.

     

Prospective comparison of <Superscript>68</Superscript>Ga-DOTATATE and <Superscript>18</Superscript>F-FDOPA PET/CT in patients with various pheochromocytomas and paragangliomas with emphasis on sporadic cases

Purpose

Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress somatostatin receptors and recent studies have already shown excellent results in the localization of these tumors using ⁶⁸Ga-labeled somatostatin analogs (⁶⁸Ga-DOTA-SSA), especially in patients with germline succinate dehydrogenase subunit B gene (SDHB) mutations and head and neck PGLs (HNPGLs). The value of ⁶⁸Ga-DOTA-SSA has to be established in sporadic cases, including PHEOs. Thus, the aim of this study was to compare ⁶⁸Ga-DOTATATE PET/CT, ¹⁸F-FDOPA PET/CT, and conventional imaging in patients with various PHEOs/PGLs with a special emphasis on sporadic cases, including those located in the adrenal gland.

Design

⁶⁸Ga-DOTATATE, ¹⁸F-FDOPA PET/CT, and conventional imaging (contrast-enhanced CT and MRI with MR angiography sequences) were prospectively performed in 30 patients (8 with SDHD mutations, 1 with a MAX mutation and 21 sporadic cases) with PHEO/PGL at initial diagnosis or relapse.

Results

The patient-based sensitivities were 93 % (28/30), 97 % (29/30), and 93 % (28/30) for ⁶⁸Ga-DOTATATE PET/CT, ¹⁸F-FDOPA PET/CT, and conventional imaging, respectively. The lesion-based sensitivities were 93 % (43/46), 89 % (41/46), and 76 % (35/46) for ⁶⁸Ga-DOTATATE PET/CT, ¹⁸F-FDOPA PET/CT, and conventional imaging respectively (p?=?0.042). ⁶⁸Ga-DOTATATE PET/CT detected a higher number of HNPGLs (30/30) than ¹⁸F-FDOPA PET/CT (26/30; p?=?0.112) and conventional imaging (24/30; p?=?0.024). ⁶⁸Ga-DOTATATE PET/CT missed two PHEOs of a few millimeters in size and a large recurrent PHEO. One lesion was considered false-positive on ⁶⁸Ga-DOTATATE PET/CT and corresponded to a typical focal lesion of fibrous dysplasia on MRI. Among the 11 lesions missed by conventional imaging, 7 were detected by conventional imaging with knowledge of the PET results (4 HNPGLs, 2 LNs, and 1 recurrent PHEO).

Conclusion

⁶⁸Ga-DOTATATE PET/CT is the most sensitive tool in the detection of HNPGLs, especially SDHD-related tumors, which may be very small and fail to concentrate sufficient ¹⁸F-FDOPA. The present study further expands the use of ⁶⁸Ga-DOTATATE for all patients with HNPGLs, regardless of their genotype. ⁶⁸Ga-DOTATATE PET/CT may be inferior to ¹⁸F-FDOPA PET/CT in the detection PHEOs.

     

Detection of recurrent prostate cancer lesions before salvage lymphadenectomy is more accurate with <Superscript>68</Superscript>Ga-PSMA-HBED-CC than with <Superscript>18</Superscript>F-Fluoroethylcholine PET/CT

Aim

[⁶⁸Ga]PSMA-HBED-CC (⁶⁸Ga-PSMA) is a novel and promising tracer for highly sensitive combined integrated positron emission tomography and X-ray computed tomography (PET/CT) diagnosis of recurrent prostate cancer (PCA). Our aim was to assess the sensitivity, specificity, positive and negative predictive value (PPV/NPV), and accuracy per lesion, as well as the positive predictive value per patient of ⁶⁸Ga-PSMA PET/CT using post-lymphadenectomy histology as a standard, and to compare these values to those obtained in a patient collective scanned using ¹⁸F-Fluoroethylcholine (¹⁸FEC) PET/CT.

Methods

Thirty eight patients had ¹⁸FEC and 28 patients had ⁶⁸Ga-PSMA. We performed a pelvic and/or retroperitoneal lymphadenectomy, if necessary supplemented by resection of locally recurrent lesions in accordance with imaging results.

Results

In 30/38 ¹⁸FEC and 23/28 ⁶⁸Ga-PSMA patients ≥1 focus of PCA was identified in postsurgical histology, leading to a per-patient PPV of 78.9 % for ¹⁸FEC and 82.1 % for ⁶⁸Ga-PSMA. In ¹⁸FEC and ⁶⁸Ga-PSMA patients, a total of 378 and 308 lymph nodes and local lesions were removed, respectively. For ¹⁸FEC and ⁶⁸for Ga-PSMA, the respective sensitivity (95 % confidence interval) was 71.2 % (64.5–79.6 %) and 86.9 % (75.8–94.2 %), specificity was 86.9 % (82.3–90.6 % ) and 93.1 % (89.2–95.9 %), PPV was 67.3 % (57.7–75.9 %) and 75.7 % (64.0–98.5 %), NPV was 88.8 % (84.4–92.3 %) and 96.6 % (93.5–98.5 %), and accuracy was 82.5 % (78.3–86.8 %) and 91.9 % (88.7 %–95.1 %).

Conclusion

In the present series Ga-PSMA PET/CT shows a better performance than FEC PET/CT with a significantly higher NPV and accuracy for the detection of locoregional recurrent and/or metastatic lesions prior to salvage lymphadenectomy.

     

Clinical Significance of Incidental Focal <Superscript>18</Superscript>F-FDG Uptake in the Spinal Cord of Patients with Cancer

Purpose

We investigated the incidence, location, and clinical significance of focal ¹⁸F-FDG uptake of the spinal cord in patients with cancer.

Methods

We reviewed the medical records of 22,937 consecutive adult patients with known or suspicious malignancy who underwent ¹⁸F-FDG PET/CT. PET/CT scans with incidental focal spinal cord uptake were selected and retrospectively reviewed to determine the presence, location, number, and maximum standardized uptake value (SUV_max) of any focal hypermetabolic lesions of the spinal cord. In subjects with focal spinal uptake, clinical characteristics and clinical follow-up results, including follow-up PET/CT, were reviewed.

Results

Incidental focal spinal cord uptake was observed in 69 of 22,937 adult patients (incidence?=?0.3%; M:F?=?31:38; age, 55.8?±?14.7 years). Seventy-eight focal hypermetabolic lesions on spinal cord in the PET/CT scans of the 69 study subjects were analyzed. The most common sites of focal spinal cord uptake were the T12 vertebra (47/78; 60.3%) and L1 vertebra (20/78; 25.6%). Multifocal cord uptake was found in 8 of 69 patients (11.6%). The average SUV_max for cord uptake was 2.5?±?0.5 (range, 1.4～3.9). There was no clinical or imaging evidence of abnormalities in the spinal cord, both at the time of PET/CT and during clinical follow-up.

Conclusions

Although incidental focal ¹⁸F-FDG uptake of the spinal cord is rare in patients with cancer, it may be physiological or benign, but it should not be considered as malignant involvement. Common sites for the uptake were in the T12 and L1 spine levels.

     

Long-term results and tolerability of tandem peptide receptor radionuclide therapy with <Superscript>90</Superscript>Y/<Superscript>177</Superscript>Lu-DOTATATE in neuroendocrine tumors with respect to the primary location: a 10-year study

Introduction

The peptide receptor radionuclide therapy (PRRT) with ⁹⁰Y and ¹⁷⁷Lu is a form of molecular targeted therapy for inoperable or disseminated neuroendocrine tumors (NET).

Aim

The aim of the study was to evaluate clinical results and long-term side effects of tandem ⁹⁰Y /¹⁷⁷Lu-DOTATATE therapy in patients with NET. Additionally, we evaluated clinical results with reference to the primary site.

Materials and methods

59 patients with disseminated NET were included in the study prospectively. 3–5 cycles of combined 1:1 ⁹⁰Y/¹⁷⁷Lu-DOTATATE (total injected activity 11.1–16.65 GBq) with mixed amino acids for kidney protection were performed.

Results

During a median follow-up of 75.8 months, the PFS was 32.2 months, and the OS was 82 months; 25 patients died. Depending on primary tumor’s site, the PFS and the OS for pancreatic NET vs. small bowel, NET vs. large bowel, NET were 30.4 vs. 29.5 vs. 40.3 and 78.9 vs. 58.1 vs. 82.5, respectively. The observed 5-year overall survival was 63%, and a 2-year risk of progression was 39.4%. The following imaging response was observed: CR in 2%, PR in 22%, SD in 65%, and PD in 6% patients. The disease control rate was 89%. The objective response rate was 24%. The PRRT was well tolerated by all patients. One patient (2%) revealed MDS, and one patient (2%) grade 3 nephrotoxicity. No other grade 3 and 4 hematological or renal toxicity was observed.

Conclusions

These results indicated the tandem ⁹⁰Y/¹⁷⁷Lu-DOTATATE therapy for patients with disseminated/inoperable NET as highly effective and safe, considering long-term side effects. In the majority of patients, clinical improvement was observed.

     

Diagnostic utility of PET/CT with <Superscript>18</Superscript>F-DOPA and <Superscript>18</Superscript>F-FDG in persistent or recurrent medullary thyroid carcinoma: the importance of calcitonin and carcinoembryonic antigen cutoff

Purpose

This study sought to evaluate and compare the utility of 18-F-fluorodihydroxyphenylalanine (¹⁸F-DOPA) and 18-F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) for identification of lesions in patients with recurrent medullary thyroid carcinoma (MTC). In addition, we analyzed the correlation between the calcitonin (Ct), carcinoembryonic antigen (CEA) levels, each doubling time (DT), and PET positivity. We evaluated the reliability of the 150 pg/mL Ct cutoff set by the American Thyroid Association guidelines for further imaging (including ¹⁸F-DOPA PET/CT).

Methods

We prospectively recruited 18 patients with recurrent MTC, identified by elevation of Ct or CEA. Each patient underwent a ¹⁸F-FDG PET/CT and a ¹⁸F-DOPA PET/CT.

Results

Abnormal uptakes were detected with ¹⁸F-DOPA (n=12) and ¹⁸F-FDG (n=9), (sensitivity of 66.7% vs. 50%; p<0.01). Twenty-eight lesions were detected with ¹⁸F-DOPA vs. 16 lesions with ¹⁸F-FDG (1.56±1.5 vs. 0.89±1.18 lesions per patient; p=0.01). None of our patients showed additional lesions with ¹⁸F-FDG in comparison to ¹⁸F-DOPA. Patient-based detection rate increased significantly with Ct levels ≥150 pg/mL vs. Ct<150 pg/mL for both ¹⁸F-DOPA (sensitivity 90.9% vs. 28.6%; p=0.013) and ¹⁸F-FDG PET/CT (sensitivity 72.7% vs. 14.3%; p=0.025). Using a CEA cutoff of ≥5 ng/mL, detection rates of ¹⁸F-DOPA and ¹⁸F-FDG PET/CT were 81.1% and 72.7%, respectively. No correlation between Ct-DT or CEA-DT and PET positivity was found. Histological confirmation was obtained in eight patients.

Conclusions

¹⁸F-DOPA PET/CT appears to be superior to ¹⁸F-FDG PET/CT in detecting and locating lesions in patients with recurrent MTC. This technique tends to be especially useful in patients with negative results in other imaging modalities and Ct≥150 pg/mL or CEA≥5 ng/mL.