<Superscript>11</Superscript>C-methionine PET/CT findings in benign brain disease

¹¹C-methionine (MET) is one of the most commonly used positron emission tomography (PET) tracers for evaluation of malignant brain tumor, with MET-PET being a sensitive technique for visualization of primary and recurrent malignant brain tumors. However, previous reports have demonstrated MET uptake in lesions associated with benign brain diseases. These diseases usually show an increase in MET uptake similar to that of malignant tumors. This pitfall in MET-PET image interpretation is important not only for nuclear medicine professionals, but also for radiologists. In this review, we demonstrate the imaging characteristics of MET uptake in benign brain disease, and recommend physician interpretation of imaging findings and disease characteristics for optimal patient management. Benign uptake must be identified to prevent misdiagnosis and unnecessary surgical operations.     

Usefulness of <Superscript>11</Superscript>C-methionine PET in the evaluation of brain lesions that are hypo- or isometabolic on <Superscript>18</Superscript>F-FDG PET

The fact that some brain tumors show hypo- or isometabolism on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) has caused problems in the detection of primary or recurrent tumors and in the differentiation from benign lesions. We investigated the usefulness of carbon-11 methionine PET in characterizing brain lesions under these conditions. 11C-methionine PET was performed in 45 patients with brain lesions (in 34 for initial diagnosis and in 11 for detection of recurrence) that showed hypo- or isometabolism compared with normal brain tissue on FDG PET. Ten minutes after the injection of 555-740 MBq of 11C-methionine, attenuation-corrected brain images were obtained with a dedicated PET scanner. The brain lesions comprised 24 gliomas, five metastatic brain tumors, four meningiomas, two other brain tumors and ten benign lesions (including three cases of cysticercosis, two cases of radiation necrosis, one tuberculous granuloma, one hemangioma, one benign cyst, and one organizing infarction). Proliferative activity was measured using the Ki-67 immunostaining method in glioma tissues. Thirty-one of 35 brain tumors (89% sensitivity) showed increased 11C-methionine uptake despite iso- or hypometabolism on FDG PET. By contrast, all ten benign lesions showed decreased or normal 11C-methionine uptake (100% specificity). Twenty-two of 24 gliomas (92%) showed increased 11C-methionine uptake, the extent and degree of which exceeded 18F-FDG uptake, and the 11C-methionine uptake correlated with the proliferation index (r=0.67). The mean (+/-SD) uptake ratios of glioma to normal brain on FDG and 11C-methionine PET were 0.92+/-0.34 and 2.54+/-1.25, respectively. All metastatic tumors except one showed intense 11C-methionine uptake in the entire tumor or in the peripheral margin of the tumor. In meningiomas, 11C-methionine uptake showed a variable increase. In conclusion, brain lesions that show hypo- or isometabolism on FDG PET can be detected and differentiated with high sensitivity and good contrast using 11C-methionine PET. 11C-methionine PET can provide additional information when used in combination with FDG PET in the evaluation of these patients.     

<Superscript>11</Superscript>C-methylaminoisobutyric acid (MeAIB) PET for evaluation of prostate cancer: compared with <Superscript>18</Superscript>F-fluorodeoxyglucose PET

Objective

α-N-methyl-¹¹C-methylaminoisobutyric acid (¹¹C-MeAIB) is a selective substrate of system A amino acid transport, and known to accumulate in malignant lesions. The aim of this study was to evaluate the utility of MeAIB PET for the assessment of prostate cancer, compared with FDG PET.

Methods

Thirty-four men (age range 57–77 years) with prostate cancer were prospectively enrolled, and underwent MeAIB PET and FDG PET between January 2011 and January 2013. MeAIB PET and FDG PET were performed at 20 and 50 min post-injection, respectively. SUVmax of the prostate was calculated, and visual analysis was conducted for MeAIB and FDG PET studies. MRI images were visually evaluated if available. All patients received total prostatectomy subsequently, and imaging findings were compared with pathological results, including T stage, Gleason score, and tumor size. The patient-based and lesion-based sensitivity and specificity were calculated according to pathological significant cancer.

Results

Mean value of SUVmax of ¹¹C-MeAIB PET and ¹⁸F-FDG PET in prostate cancer were 3.18 (±1.90, range; 1.55–9.57) and 3.88 (±2.85, range; 2.04–14.47). MeAIB PET and FDG PET were positive by visual analysis in 47.1 % (16/34) and 44.1 % (15/34) of the patients. MRI was positive in 51.5 % (17/33). Pathological stage and Gleason score were as follows: Stage 2 (n = 23), 3 (n = 8), and 4 (n = 3); Gleason score 6 (n = 13), 7 (n = 16), 8 (n = 3), and 9 (n = 2). The sensitivities tended to be higher according to higher pathological T stage or Gleason sum score for both MeAIB and FDG PET studies. Visual analysis of both MeAIB PET and FDG PET had significant correlation with extraprostatic extension (p < 0.05). MeAIB PET and FDG PET had complementary results by visual analysis in the assessment of prostate cancer. The patient-based sensitivity of MeAIB PET, FDG PET, and MRI were 51.6, 48.4, and 56.7 %, respectively. The patient-based specificity of these modalities was 100 % for each modality.

Conclusions

MeAIB PET has better diagnostic results than FDG PET for the assessment of significant prostate cancer, and these PET studies showed complementary results. MRI has even better diagnostic results than ¹¹C-MeAIB PET. MeAIB accumulates in prostate cancer, which indicates that the system A amino acid transport pathway is activated in prostate cancer.

     

<Superscript>11</Superscript>C-methionine uptake in cerebrovascular disease: A comparison with<Superscript>18</Superscript>F-FDG PET and<Superscript>99m</Superscript>Tc-HMPAO SPECT

OBJECTIVES: Carbon-11-L-methyl-methionine (11C-methionine) has been reported to be useful for evaluating brain tumors, but several other brain disorders have also shown signs of high methionine uptake. We retrospectively evaluated the significance of 11C-methionine uptake in cerebrovascular diseases, and also compared our results with those for 18F-FDG PET and 99mTc-HMPAO SPECT. METHODS: Seven patients, including 3 patients with a cerebral hematoma and 4 patients with a cerebral infarction, were examined. All 7 patients underwent both 11C-methionine PET and 99mTc-HMPAO SPECT, and 6 of them underwent 18F-FDG PET. RESULTS: A high 11C-methionine uptake was observed in all 3 patients with cerebral hematoma. Increased 99mTc-HMPAO uptake was observed in 2 out of 3 patients, and all 3 patients had decreased 18F-FDG uptake. Of 4 patients with a cerebral infarction, high 11C-methionine uptake was observed in 3. Increased 99mTc-HMPAO uptake was also observed in one patient, whereas 3 patients had decreased 18F-FDG uptake. CONCLUSIONS: We should keep in mind that high 11C-methionine uptake is frequently observed in cerebrovascular diseases. CVD should therefore be included in the differential diagnosis when encounting patients with a high 11C-methionine uptake.     

PET of hypoxia and perfusion with 62Cu-ATSM and 62Cu-PTSM using a 62Zn/62Cu generator

OBJECTIVE: Copper-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) and copper-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (Cu-PTSM) are being studied as potential markers of hypoxia and perfusion, respectively. The use of short-lived radionuclides (e.g., 62Cu) has advantages for clinical PET, including a lower radiation dose than long-lived radionuclides and serial imaging capability. A 62Zn/62Cu microgenerator and rapid synthesis kits now provide a practical means of producing 62Cu-PTSM and 62Cu-ATSM on-site. Tumors can be characterized with 62Cu-PTSM, 62Cu-ATSM, and 18F-FDG PET scans during one session. We present the initial clinical data in two patients with lung neoplasms. CONCLUSION: Hypoxia and perfusion are important parameters in tumor physiology and can have major implications in diagnosis, prognosis, treatment planning, and response to therapy. We have shown the feasibility of performing 62Cu-ATSM and 62Cu-PTSM PET together with FDG PET/CT during a single imaging session to provide information on both perfusion and hypoxia and tumor anatomy and metabolism.     

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.

     

In vivo assessment of tumor hypoxia in lung cancer with <Superscript>60</Superscript>Cu-ATSM

Tumor hypoxia is recognized as an important determinant of response to therapy. In this study we investigated the feasibility of clinical imaging with copper-60 diacetyl-bis( N(4)-methylthiosemicarbazone) ((60)Cu-ATSM) in patients with non-small-cell lung cancer (NSCLC) and also assessed whether pretreatment tumor uptake of (60)Cu-ATSM predicts tumor responsiveness to therapy. Nineteen patients with biopsy-proved NSCLC were studied by positron emission tomography (PET) with (60)Cu-ATSM before initiation of therapy. (60)Cu-ATSM uptake was evaluated semiquantitatively by determining the tumor-to-muscle activity ratio (T/M). All patients also underwent PET with fluorine-18 fluorodeoxyglucose (FDG) prior to institution of therapy. The PET results were correlated with follow-up evaluation (2-46 months). It was demonstrated that PET imaging with (60)Cu-ATSM in patients with NCSLC is feasible. The tumor of one patient had no discernible (60)Cu-ATSM uptake, whereas the tumor uptake in the remaining patients was variable, as expected. Response was evaluated in 14 patients; the mean T/M for (60)Cu-ATSM was significantly lower in responders (1.5+/-0.4) than in nonresponders (3.4+/-0.8) (P=0.002). However, the mean SUV for (60)Cu-ATSM was not significantly different in responders (2.8+/-1.1) and nonresponders (3.5+/-1.0) ( P=0.2). An arbitrarily selected T/M threshold of 3.0 discriminated those likely to respond to therapy: all eight responders had a T/M <3.0 and all six nonresponders had a T/M > or =3.0. Tumor SUV for FDG was not significantly different in responders and nonresponders (P=0.7) and did not correlate with (60)Cu-ATSM uptake (r=0.04; P=0.9). (60)Cu-ATSM-PET can be readily performed in patients with NSCLC and the tumor uptake of (60)Cu-ATSM reveals clinically unique information about tumor oxygenation that is predictive of tumor response to therapy.     

Dual-time-point <Superscript>18</Superscript>F-FDG PET imaging for diagnosis of disease type and disease activity in patients with idiopathic interstitial pneumonia

Purpose  Individual clinical courses of idiopathic interstitial pneumonia (IIP) are variable and difficult to predict because the pathology and disease activity are contingent, and chest computed tomography (CT) provides little information about disease activity. In this study, we applied dual-time-point [¹⁸F]-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) positron emission tomography (PET), commonly used for diagnosis of malignant tumours, to the differential diagnosis and prediction of disease progression in IIP patients. Methods  Fifty patients with IIP, including idiopathic pulmonary fibrosis (IPF, n = 21), non-specific interstitial pneumonia (NSIP, n = 18) and cryptogenic organizing pneumonia (COP, n = 11), underwent ¹⁸F-FDG PET examinations at two time points: scan 1 at 60 min (early imaging) and scan 2 at 180 min (delayed imaging) after ¹⁸F-FDG injection. The standardized uptake values (SUV) at the two points and the retention index (RI-SUV) calculated from them were evaluated and compared with chest CT findings, disease progression and disease types. To evaluate short-term disease progression, all patients were examined by pulmonary function test every 3 months for 1 year after ¹⁸F-FDG PET scanning. Results  The early SUV for COP (2.47 ± 0.74) was significantly higher than that for IPF (0.99 ± 0.29, p = 0.0002) or NSIP (1.22 ± 0.44, p= 0.0025). When an early SUV cut-off value of 1.5 and greater was used to distinguish COP from IPF and NSIP, the sensitivity, specificity and accuracy were 90.9, 94.3 and 93.5%, respectively. The RI-SUV for IPF and NSIP lesions was significantly greater in patients with deteriorated pulmonary function after 1 year of follow-up (progressive group, 13.0 ± 8.9%) than in cases without deterioration during the 1-year observation period (stable group, −16.8 ± 5.9%, p < 0.0001). However, the early SUV for all IIP types provided no additional information of disease progression. When an RI-SUV cut-off value of 0% and greater was used to distinguish progressive IIPs from stable IIPs, the sensitivity, specificity and accuracy were 95.5, 100 and 97.8%, respectively. Conclusion  Early SUV and RI-SUV obtained from dual-time-point ¹⁸F-FDG PET are useful parameters for the differential diagnosis and prediction of disease progression in patients with IIP.     

<Superscript>11</Superscript>C-acetate PET imaging of lung cancer: comparison with <Superscript>18</Superscript>F-FDG PET and <Superscript>99m</Superscript>Tc-MIBI SPET

Recently carbon-11 acetate (AC) positron emission tomography (PET) has been reported to be of clinical value for the diagnosis of cancer that is negative on fluorine-18 fluorodeoxyglucoce (FDG) PET. We investigated the uptake of AC in lung cancer to determine whether this tracer is of potential value for tumour detection and characterisation, and to compare AC PET imaging with FDG PET and technetium-99m sestamibi (MIBI) single-photon emission tomography (SPET). Twenty-three patients with 25 lung cancers underwent AC and FDG PET. Twenty of 23 patients were also investigated with MIBI SPET. Dynamic images were acquired for 26 min after the injection of 555 MBq of AC. Standardised uptake values (SUVs) and/or tumour to non-tumour activity ratios (T/N) for each tumour were investigated at 10–20 min after AC administration, 40–60 min after administration of 185 MBq FDG and 15–45 min after administration of 555 MBq MIBI. Twenty lung cancers were resected surgically, and the degree of tracer uptake in the primary lesion was correlated with histopathological features (cell dedifferentiation and aggressiveness) and prognosis. Rapid uptake of AC followed by extremely slow clearance was observed. For the purpose of tumour identification, AC PET was inferior to FDG PET in 8 of 25 (32%) lung cancers, and the T/N of AC was lower than that of FDG. However, AC PET was superior to FDG PET in the identification of a slow-growing tumour (bronchiolo-alveolar carcinoma). There was a positive correlation between AC uptake (T/N) and MIBI uptake (T/N) (r=0.799, P<0.0001). A positive correlation was not observed between either AC or MIBI uptake and the degree of cell dedifferentiation in lung adenocarcinomas, whereas FDG uptake did correlate with the degree of cell dedifferentiation. In lung adenocarcinoma, there was a weak correlation between aggressiveness and FDG uptake, but no correlation was evident for AC and MIBI. In addition, a positive correlation was not observed between AC or MIBI uptake and postoperative recurrence in lung adenocarcinoma, whereas FDG uptake did correlate with postoperative recurrence. Thus, the greater the FDG uptake, the higher the malignant grade. In conclusion, for the purpose of tumour identification, AC PET was inferior to FDG PET but superior to MIBI SPET. Neither AC nor MIBI uptake reflects the malignant grade in lung adenocarcinoma, whereas FDG uptake does. AC PET is less diagnostically informative than FDG PET in patients with lung cancer. However, AC PET may play a complementary role in the identification of low-grade malignancies that are not FDG avid.     

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.

     

Detection of gastric cancer using <Superscript>18</Superscript>F-FLT PET: comparison with <Superscript>18</Superscript>F-FDG PET

Purpose  We prospectively investigated the feasibility of 3′-deoxy-3′-¹⁸F-fluorothymidine (FLT) positron emission tomography (PET) for the detection of gastric cancer, in comparison with 2-deoxy-2-¹⁸F-fluoro-d-glucose (FDG) PET, and determined the degree of correlation between the two radiotracers and proliferative activity as indicated by Ki-67 index. Methods  A total of 21 patients with newly diagnosed advanced gastric cancer were examined with FLT PET and FDG PET. Tumour lesions were identified as areas of focally increased uptake, exceeding that of surrounding normal tissue. For semiquantitative analysis, the maximal standardized uptake value (SUV) was calculated. Results  For detection of advanced gastric cancer, the sensitivities of FLT PET and FDG PET were 95.2% and 95.0%, respectively. The mean (±SD) SUV for FLT (7.0 ± 3.3) was significantly lower than that for FDG (9.4 ± 6.3 p < 0.05). The mean FLT SUV and FDG SUV in nonintestinal tumours were higher than in intestinal tumours, although the difference was not statistically significant. The mean (±SD) FLT SUV in poorly differentiated tumours (8.5 ± 3.5) was significantly higher than that in well and moderately differentiated tumours (5.3 ± 2.1; p < 0.04). The mean FDG SUV in poorly differentiated tumours was higher than in well and moderately differentiated tumours, although the difference was not statistically significant. There was no significant correlation between Ki-67 index and either FLT SUV or FDG SUV. Conclusion  FLT PET showed as high a sensitivity as FDG PET for the detection of gastric cancer, although uptake of FLT in gastric cancer was significantly lower than that of FDG.     

Feasibility of dynamic stress <Superscript>201</Superscript>Tl/rest <Superscript>99m</Superscript>Tc-tetrofosmin single photon emission computed tomography for quantification of myocardial perfusion reserve in patients with stable coronary artery disease

Purpose

We evaluated the feasibility of dynamic stress ²⁰¹Tl/rest ^99mTc-tetrofosmin SPECT imaging using a cardiac camera equipped with cadmium-zinc-telluride detectors for the quantification of myocardial perfusion reserve (MPR).

Methods

Subjects with stable known or suspected coronary artery disease (CAD) who had undergone or were scheduled to undergo fractional flow reserve (FFR) measurement were prospectively enrolled. Dynamic stress ²⁰¹Tl/rest ^99mTc-tetrofosmin SPECT imaging was performed using a dedicated multiple pinhole SPECT camera with cadmium-zinc-telluride detectors. MPR was derived using Corridor4DM software.

Results

A total of 34 subjects were enrolled (25 men and 9 women; mean age 60.4 years). FFR was measured in 65 coronary arteries with intermediate lesions. The average global MPR was 2.58?±?1.03. Global MPR was associated with the extent of CAD (P?=?0.028) and global summed stress score (r?=??0.60, P?<?0.001). Regional MPR showed a significant correlation with diameter stenosis (r?=??0.57, P?<?0.001), minimum lumen diameter (r?=?0.50, P?<?0.001), summed stress score (r?=??0.52, P?<?0.001) and FFR (r?=?0.52, P?<?0.001). The area under the receiver operating characteristic curve of MPR for the diagnosis of functionally significant stenosis (FFR ≤0.8) was 0.79 (P?<?0.001). The sensitivity and specificity of regional MPR were 67% and 83%, respectively, using a cut-off value of 2.0.

Conclusion

Dynamic stress ²⁰¹Tl/rest ^99mTc-tetrofosmin SPECT imaging and quantification of MPR is feasible in patients with stable CAD. The preliminary results of this study in a small number of patients require confirmation in a larger cohort to determine their implications for bolstering the role of SPECT imaging in the diagnosis and risk prediction of CAD.

     

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

Purpose

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

Methods

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

Results

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

Conclusion

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

     

Value of <Superscript>11</Superscript>C-choline PET and PET/CT in patients with suspected prostate cancer

Purpose: The value and limitations of ¹¹C-choline PET and PET/CT for the detection of prostate cancer remain controversial. The aim of this study was to investigate the diagnostic efficacy of ¹¹C-choline PET and PET/CT in a large group of patients with suspected prostate cancer. Methods: Fifty-eight patients with clinical suspicion of prostate cancer underwent ¹¹C-choline PET (25/58, Siemens ECAT Exact HR+) or PET/CT (33/58, Philips Gemini) scanning. On average, 500 MBq of ¹¹C-choline was administered intravenously. Studies were interpreted by raters blinded to clinical information and other diagnostic procedures. Qualitative image analysis as well as semiquantitative SUV measurement was carried out. The reference standard was histopathological examination of resection specimens or biopsy. Results: Prevalence of prostate cancer in this selected patient population was 63.8% (37/58). ¹¹C-choline PET and PET/CT showed a sensitivity of 86.5% (32/37) and a specificity of 61.9% (13/21) in the detection of the primary malignancy. With regard to metastatic spread, PET showed a per-patient sensitivity of 81.8% (9/11) and produced no false positive findings. Conclusion: Based on our findings, differentiation between benign prostatic changes, such as benign prostatic hyperplasia or prostatitis, and prostate cancer is feasible in the majority of cases when image interpretation is primarily based on qualitative characteristics. SUV_max may serve as guidance. False positive findings may occur due to an overlap of ¹¹C-choline uptake between benign and malignant processes. By providing functional information regarding both the primary malignancy and its metastases, ¹¹C-choline PET may prove to be a useful method for staging prostate cancer.     

<Superscript>68</Superscript>Ga-PSMA-HBED-CC PET imaging in breast carcinoma patients

Background

To report on imaging findings using ⁶⁸Ga-PSMA-HBED-CC PET in a series of 19 breast carcinoma patients.

Methods

⁶⁸Ga-PSMA-HBED-CC PET imaging results obtained were compared to routinely performed staging examinations and analyzed as to lesion location and progesterone receptor status.

Results

Out of 81 tumor lesions identified, 84% were identified on ⁶⁸Ga-PSMA-HBED-CC PET. ⁶⁸Ga-PSMA-HBED-CC SUVmean values of distant metastases proved significantly higher (mean, 6.86, SD, 5.68) when compared to those of primary or local recurrences (mean, 2.45, SD, 2.55, p?=?0.04) or involved lymph nodes (mean, 3.18, SD, 1.79, p?=?0.011). SUVmean values of progesterone receptor-positive lesions proved not significantly different from progesterone receptor-negative lesions. SUV values derived from FDG PET/CT, available in seven patients, and ⁶⁸Ga-PSMA-HBED-CC PET/CT imaging proved weakly correlated (r?=?0.407, p?=?0.015).

Conclusions

⁶⁸Ga-PSMA-HBED-CC PET/CT imaging in breast carcinoma confirms the reported considerable variation of PSMA expression on human solid tumors using immunohistochemistry.

     

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

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

<Superscript>18</Superscript>F-FDG PET independently predicts survival in patients with cholangiocellular carcinoma treated with <Superscript>90</Superscript>Y microspheres

Purpose  

⁹⁰Y radioembolization has emerged as a valuable therapy for intrahepatic cholangiocellular carcinomas (ICC). We aimed to evaluate the prognostic power of FDG PET/CT and that of pretherapeutic scintigraphy with ^99mTc-labelled macroagglutinated albumin (MAA), an index of tumour vascularization.     

PET imaging of hepatocellular carcinoma with <Superscript>18</Superscript>F-fluoroethylcholine and <Superscript>11</Superscript>C-choline

Purpose  

Choline-based radiotracers have been studied for PET imaging of hepatocellular carcinoma (HCC). Using an ¹⁸F-labeled choline analog, instead of the ¹¹C-labeled native choline, would facilitate its widespread use in the clinic. In this study, PET with ¹⁸F-fluoroethylcholine (FEC) and ¹¹C-choline (CHOL) were compared using an animal model of HCC. The effects of fasting on the performance of choline-based tracers were also investigated.     

Comparison of <Superscript>18</Superscript>F-FLT PET and <Superscript>18</Superscript>F-FDG PET for preoperative staging in non-small cell lung cancer

Purpose The nucleoside analog 3′-deoxy-3′-¹⁸F-fluorothymidine (FLT) has been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively compared the diagnostic efficacy of FLT PET with that of 2-deoxy-2-¹⁸F-fluoro-d-glucose (FDG) PET for the preoperative nodal and distant metastatic staging of non-small cell lung cancer (NSCLC). Methods A total of 34 patients with NSCLC underwent FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. The PET images were evaluated qualitatively for regions of focally increased metabolism. For visualized primary tumors, the maximum standardized uptake value (SUV) was calculated. Nodal stages were determined by using the American Joint Committee on Cancer staging system and surgical and histologic findings reference standards. Results For the depiction of primary tumor, sensitivity of FLT PET was 67%, compared with 94% for FDG PET (P = 0.005). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for lymph node staging on a per-patient basis were 57, 93, 67, 89, and 85%, respectively, with FLT PET and 57, 78, 36, 91, and 74%, respectively, with FDG PET (P > 0.1 for all comparisons). Two of the three distant metastases were detected with FLT and FDG PET. Conclusion In NSCLC, FLT PET showed better (although not statistically significant) specificity, positive predictive value and accuracy for N staging on a per-patient basis than FDG PET. However, FDG PET was found to have higher sensitivity for depiction of primary tumor than FLT PET.