<Superscript>68</Superscript>Gallium-Arginine-Glycine-Aspartic Acid and <Superscript>18</Superscript>F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Chondroblastic Osteosarcoma of the Skull

We report the case of a 32 year-old male with Chondroblastic Osteosarcoma of the skull, which was imaged with both ¹⁸[F]fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) and ⁶⁸Gallium-arginine-glycine-aspartic acid (⁶⁸Ga-RGD) PET/CT. The ¹⁸F-FDG PET/CT did not demonstrate the tumour, whereas the ⁶⁸Ga-RGD PET/CT clearly depicted a left-sided frontal tumour. ⁶⁸Ga-RGD PET/CT may be a clinically useful imaging modality for early detection of recurrent osteosarcoma, considering the limitations of ¹⁸F-FDG PET in a setting of low glycolytic activity.     

Bone and Calcified Soft Tissue Metastases of Medullary Thyroid Carcinoma Better Characterized on <Superscript>18</Superscript>F-Fluoride PET/CT than on <Superscript>68</Superscript>Ga-Dotatate PET/CT

Herein, we report a case of a 19-year-old man with multiple endocrine neoplasia type 2B (MEN2B) and medullary thyroid carcinoma (MTC) diagnosed when he was 12 years of age. The patient had previously undergone total thyroidectomy, cervical radiotherapy, and chemotherapy. He progressed with known bone, pulmonary, and lymph node metastases and was scanned with ¹⁸F-fluoride (¹⁸F-NaF) and ⁶⁸Ga-dotatate whole-body positron emission tomography/computed tomography (PET/CT) for metastatic disease monitoring. We found that the MTC bone metastases and soft tissue calcified metastases were better characterized on ¹⁸F-NaF PET/CT than on ⁶⁸Ga-dotatate PET/CT. This case illustrates that the ¹⁸F-NaF PET/CT could be helpful not only to the detection of bone metastases but also to the detection of calcified soft tissue metastases in patients with MTC.     

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.

     

Acquisition with <Superscript>11</Superscript>C-choline and <Superscript>18</Superscript>F-fluorocholine PET/CT for patients with biochemical recurrence of prostate cancer: a systematic review and meta-analysis

The objective of the systematic review and meta-analysis was to evaluate whether the choice between two radiotracers, ¹¹C-choline (¹¹C-cho) and ¹⁸F-fluorocholine (¹⁸F-FCH) for PET/CT, and different acquisition protocols contributed to detect metastases for patients with biochemical recurrence of prostate cancer after radical prostatectomy or radiotherapy. We searched in January 2016 in Pubmed and Embase for articles that had used radiolabeled choline PET/CT in restaging. The meta-analysis evaluated technical and clinical aspects. Across 18 articles 1 219 of 2 213 patients (54.9 %) had a positive radiolabeled PET/CT image. Mean of the mean/median restaging PSA levels was 3.6 ± 2.7 ng/mL (range 0.5–10.7 ng/mL). Six articles with ¹¹C-cho PET/CT had a radiation activity of 561 ± 122 MBq and it was 293 ± 47 MBq in 12 articles with ¹⁸F-FCH PET/CT. The difference was significant (P = 0.007, t test). Uptake time was 5 min in articles with ¹¹C-cho PET/CT and it was 29 ± 24 min in articles with ¹⁸F-FCH PET/CT. The difference was significant (P = 0.02, t test). Thereby the detection rates of metastatic sites in articles with ¹¹C-cho (30 ± 5 %) and ¹⁸F-FCH (39 ± 5 %) did not differ significantly (P = 0.26, t test). In linear regression analyses of the articles, the radiation activity of ¹¹C-cho and ¹⁸F-FCH was not significantly associated with the detection rate of metastatic sites (P = 0.75 and P = 0.60). Restaging with radiolabeled choline PET/CT detected metastatic sites for patients with biochemical recurrence and PSA levels of 1–10 ng/mL at clinically relevant level. The choice between the two choline radiotracers and different acquisition protocols had no significant impact on detection.     

<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.

     

<Superscript>18</Superscript>F-FDG PET/CT for the Diagnosis of Malignant and Infectious Complications After Solid Organ Transplantation

Purpose

Infection and malignancy represent two common complications after solid organ transplantation, which are often characterized by poorly specific clinical symptomatology. Herein, we have evaluated the role of ¹⁸F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) in this clinical setting.

Methods

Fifty-eight consecutive patients who underwent FDG PET/CT after kidney, lung or heart transplantation were included in this retrospective analysis. Twelve patients underwent FDG PET/CT to strengthen or confirm a diagnostic suspicion of malignancies. The remaining 46 patients presented with unexplained inflammatory syndrome, fever of unknown origin (FUO), CMV or EBV seroconversion during post-transplant follow-up without conclusive conventional imaging. FDG PET/CT results were compared to histology or to the finding obtained during a clinical/imaging follow-up period of at least 6 months after PET/CT study.

Results

Positive FDG PET/CT results were obtained in 18 (31 %) patients. In the remaining 40 (69 %) cases, FDG PET/CT was negative, showing exclusively a physiological radiotracer distribution. On the basis of a patient-based analysis, FDG PET/CT’s sensitivity, specificity, PPV and NPV were respectively 78 %, 90 %, 78 % and 90 %, with a global accuracy of 86 %. FDG PET/CT was true positive in 14 patients with bacterial pneumonias (n?=?4), pulmonary fungal infection (n?=?1), histoplasmosis (n?=?1), cutaneous abscess (n?=?1), inflammatory disorder (sacroiliitis) (n?=?1), lymphoma (n?=?3) and NSCLC (n?=?3). On the other hand, FDG PET/CT failed to detect lung bronchoalveolar adenocarcinoma, septicemia, endocarditis and graft-versus-host disease (GVHD), respectively, in four patients. FDG PET/CT contributed to adjusting the patient therapeutic strategy in 40 % of cases.

Conclusions

FDG PET/CT emerges as a valuable technique to manage complications in the post-transplantation period. FDG PET/CT should be considered in patients with severe unexplained inflammatory syndrome or FUO and inconclusive conventional imaging or to discriminate active from silent lesions previously detected by conventional imaging particularly when malignancy is suspected.

     

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.

     

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.

     

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.

     

Direct comparison of <Superscript>68</Superscript>Ga-DOTA-TOC and <Superscript>18</Superscript>F-FDG PET/CT in the follow-up of patients with neuroendocrine tumour treated with the first full peptide receptor radionuclide therapy cycle

Purpose

To determine the value of ⁶⁸Ga-DOTA-TOC and ¹⁸F-FDG PET/CT for initial and follow-up evaluation of patients with neuroendocrine tumour (NET) treated with peptide receptor radionuclide therapy (PRRT).

Methods

We evaluated 66 patients who had histologically proven NET and underwent both PRRT and three combined ⁶⁸Ga-DOTA-TOC and ¹⁸F-FDG PET/CT studies. ⁶⁸Ga-DOTA-TOC PET/CT was performed before PRRT, 3 months after completion of PRRT and after a further 6 – 9 months. ¹⁸F-FDG PET/CT was done within 2 months of ⁶⁸Ga-DOTA-TOC PET/CT. Follow-up ranged from 11.8 to 80.0 months (mean 34.5 months).

Results

All patients were ⁶⁸Ga-DOTA-TOC PET-positive initially and at follow-up after the first full PRRT cycle. Overall, 62 of the 198 ¹⁸F-FDG PET studies (31 %) were true-positive in 38 of the 66 patients (58 %). Of the 66 patients, 28 (5 grade 1, 23 grade 2) were ¹⁸F-FDG-negative initially and during follow-up (group 1), 24 (5 grade 1, 13 grade 2, 6 grade 3) were ¹⁸F-FDG-positive initially and during follow-up (group 2), 9 patients (2 grade 1, 6 grade 2, 1 grade 3) were ¹⁸F-FDG-negative initially but ¹⁸F-FDG-positive during follow-up (group 3), and 5 patients (all grade 2) were ¹⁸F-FDG-positive initially but ¹⁸F-FDG-negative during follow-up (group 4).¹⁸F-FDG PET showed more and/or larger metastases than ⁶⁸Ga-DOTA-TOC PET in five patients of group 2 and four patients of group 3, all with progressive disease. In three patients with progressive disease who died during follow-up tumour SUVmax increased by 41 – 82 % from the first to the last follow-up investigation.

Conclusion

In NET patients, the presence of ¹⁸F-FDG-positive tumours correlates strongly with a higher risk of progression. Initially, patients with ¹⁸F-FDG-negative NET may show ¹⁸F-FDG-positive tumours during follow-up. Also patients with grade 1 and grade 2 NET may have ¹⁸F-FDG-positive tumours. Therefore, ¹⁸F-FDG PET/CT is a complementary tool to ⁶⁸Ga-DOTA-TOC PET/CT with clinical relevance for molecular investigation.

     

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.

     

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.

     

Giant Cell Tumor with Secondary Aneurysmal Bone Cyst Shows Heterogeneous Metabolic Pattern on <Superscript>18</Superscript>F-FDG PET/CT: A Case Report

Giant cell tumor (GCT) is a generally benign bone tumor accounting for approximately 5 % of all primary bone neoplasms. Cystic components in GCTs that indicate secondary aneurysmal bone cysts (ABCs) are reported in 14 % of GCTs. Although both of them have been described separately in previous reports that may show considerable fluorodeoxyglucose (FDG) uptake despite their benign nature, the findings of GCT with secondary ABC on ¹⁸F-FDG positron emission tomography/computed tomography (PET/CT) have not been well-known. We report a case of GCT with secondary ABC in a 26-year-old woman. ¹⁸F-FDG PET/CT revealed a heterogeneous hypermetabolic lesion in the left proximal femur with the maximum standardized uptake value of 4.7. The solid components of the tumor showed higher FDG uptake than the cystic components. These observations suggest that the ABC components in GCTs show heterogeneous metabolic patterns on ¹⁸F-FDG PET/CT.     

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.

     

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.

     

The utility of PET/CT with <Superscript>68</Superscript>Ga-DOTATOC in sarcoidosis: comparison with <Superscript>67</Superscript>Ga-scintigraphy

Objective

This study was designed to compare the clinical efficacy of ⁶⁸Ga-DOTA-Tyr-octreotide (DOTATOC)-positron emission tomography (PET)/computed tomography (CT) with that of conventional ⁶⁷Ga-scintigraphy (GS), and to correlate quantitative parameters on DOTATOC-PET/CT with clinical data, in patients with sarcoidosis.

Methods

Twenty patients who were histologically and/or clinically diagnosed with sarcoidosis and underwent both DOTATOC-PET/CT and GS were analyzed in this study. The numbers of patients with positive findings for each organ were determined. The total numbers of involved nodal areas in the chest, as determined by DOTATOC-PET and gallium single-photon emission tomography (Ga-SPECT), were compared. The correlations between quantitative parameters on PET and clinical laboratory data were evaluated.

Results

DOTATOC-PET/CT was positive in 19 patients, being negative in only one patient with chronic inactive sarcoidosis, whereas GS was positive in 17 patients. DOTATOC-PET/CT visualized more lesions in lymph nodes, uvea, and muscles than did Ga-scintigraphy and identified more involved areas than did GS-SPECT (p < 0.0001). Whole-body active lesion volume showed a significant, but moderate correlation with angiotensin-converting enzyme level (ρ = 0.64, p = 0.0044).

Conclusions

PET/CT with DOTATOC may be superior to conventional GS in detecting sarcoidosis lesions, especially in lymph nodes, uvea, and muscles. Volumetric parameters in DOTATOC-PET/CT may be helpful in estimating the activity of sarcoidosis.

     

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.

     

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.

     

Evaluation of <Superscript>18</Superscript>F-FDG PET/CT Parameters for Detection of Lymph Node Metastasis in Cutaneous Melanoma

Purpose

The purpose of this study was to investigate the value of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) parameters in the detection of regional lymph node (LN) metastasis in patients with cutaneous melanoma.

Methods

We evaluated patients with cutaneous melanoma who underwent FDG PET/CT for initial staging or recurrence evaluation. A total of 103 patients were enrolled, and 165 LNs were evaluated. LNs that were confirmed pathologically or by follow-up imaging were included in this study. PET parameters, including maximum standardized uptake value (SUVmax), total lesion glycolysis and tumour-to-liver ratio, were used to determine the presence of metastases, and the results were compared with CT-determined LN metastasis. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values of the FDG PET parameters.

Results

A total of 93 LNs were malignant, and 84 LNs were smaller than 10 mm. In all 165 LNs, an SUVmax of >2.51 showed a sensitivity of 73.1%, a specificity of 88.9%, and an accuracy of 80.0% in detecting metastatic LNs. CT showed a higher specificity (87.3%) and lower accuracy (65.5%). For non-enlarged regional LNs (<10 mm), an SUVmax cut-off value of 1.4 showed the highest negative predictive value (81.3%). For enlarged LNs (≥10 mm), an SUVmax cut-off value of 2.4 showed the highest sensitivity (90.7%) and accuracy (88.9%) in detecting metastatic LNs.

Conclusions

In patients with cutaneous melanoma, an SUVmax of >2.4 showed a high sensitivity (91%) and accuracy (89%) in detecting metastasis in LNs ≥1 cm, and LNs <1 cm with an SUVmax <1.4 were likely to be benign.

     

Prospective head-to-head comparison of <Superscript>11</Superscript>C-choline-PET/MR and <Superscript>11</Superscript>C-choline-PET/CT for restaging of biochemical recurrent prostate cancer

Purpose

Whole-body integrated ¹¹C-choline PET/MR might provide advantages compared to ¹¹C-choline PET/CT for restaging of prostate cancer (PC) due to the high soft-tissue contrast and the use of multiparametric MRI, especially for detection of local recurrence and bone metastases.

Materials and methods

Ninety-four patients with recurrent PC underwent a single-injection/dual-imaging protocol with contrast-enhanced PET/CT followed by fully diagnostic PET/MR. Imaging datasets were read separately by two reader teams (team 1 and 2) assessing the presence of local recurrence, lymph node and bone metastases in predefined regions using a five-point scale. Detection rates were calculated. The diagnostic performance of PET/CT vs. PET/MR was compared using ROC analysis. Inter-observer and inter-modality variability, radiation exposure, and mean imaging time were evaluated. Clinical follow-up, imaging, and/or histopathology served as standard of reference (SOR).

Results

Seventy-five patients qualified for the final image analysis. A total of 188 regions were regarded as positive: local recurrence in 37 patients, 87 regions with lymph node metastases, and 64 regions with bone metastases. Mean detection rate between both readers teams for PET/MR was 84.7% compared to 77.3% for PET/CT (p > 0.05). Local recurrence was identified significantly more often in PET/MR compared to PET/CT by team 1. Lymph node and bone metastases were identified significantly more often in PET/CT compared to PET/MR by both teams. However, this difference was not present in the subgroup of patients with PSA values ≤2 ng/ml.Inter-modality and inter-observer agreement (K > 0.6) was moderate to substantial for nearly all categories. Mean reduction of radiation exposure for PET/MR compared to PET/CT was 79.7% (range, 72.6–86.2%). Mean imaging time for PET/CT was substantially lower (18.4 ± 0.7 min) compared to PET/MR (50.4 ± 7.9 min).

Conclusions

¹¹C-choline PET/MR is a robust imaging modality for restaging biochemical recurrent PC and interpretations between different readers are consistent. It provides a higher diagnostic value for detecting local recurrence compared to PET/CT with the advantage of substantial dose reduction. Drawbacks of PET/MR are a substantially longer imaging time and a slight inferiority in detecting bone and lymph node metastases in patients with PSA values >2 ng/ml. Thus, we suggest the use of ¹¹C-choline PET/MR especially for patients with low (≤2 ng/ml) PSA values, whereas PET/CT is preferable in the subgroup with higher PSA values.