PET Examinations Research Articles

Metabolism of Epidermal Growth Factor Receptor Targeting Probe [11C]PD153035: Impact on Biodistribution and Tumor Uptake in Rats

Several tracers have been evaluated as probes for noninvasive epidermal growth factor receptor (EGFR) quantification with PET. One of the most promising candidates is the (11)C-labeled analog of the EGFR tyrosine kinase inhibitor PD153035. However, previous in vitro studies indicated extensive metabolism of the tracer, which could be disadvantageous for the assessment of receptor density in vivo. The aim of this study was to investigate the in vivo metabolism of [(11)C]PD153035 to determine whether alterations in metabolite formation are accompanied by changes in biodistribution and tumor uptake. EGFR-overexpressing human epidermoid carcinoma xenografts in rats were used in all examinations of tumor uptake. Cytochrome P450 enzymes of subfamilies CYP2D and CYP3A were inhibited before intravenous injection of [(11)C]PD153035 into healthy and tumor-bearing male rats. Samples were taken from arterial blood and urine, and the occurrence of radioactive metabolites was assessed with radio-high-performance liquid chromatography. Dynamic PET examinations of healthy and tumor-bearing animals were performed. In 1 rat, the effect of local intraarterial administration was examined. [(11)C]PD153035 labeled at position 6 was metabolized extensively in vivo in male rats, resulting in very low levels of the intact tracer in plasma only minutes after injection. The major identified radiolabeled metabolites found were the N-oxide and metabolites arising from O demethylation at position 7. They were reduced by inhibition of CYP2D and CYP3A enzymes. PET revealed enzyme activity-dependent changes in the radioactivity distribution in the liver and tumors. Local administration of [(11)C]PD153035 greatly increased radioactivity levels in the adjacent tumor compared with levels typically found after intravenous administration. The highest tumor-to-muscle ratio at 60 min after intravenous injection was found in the untreated animals, whereas the overall highest ratio was found in the tumor near the intraarterial administration site. We suggest that the metabolism of [(11)C]PD153035 should be taken into consideration when this tracer is used to quantify EGFR expression, as our results indicated that the distribution of radioactivity to EGFR-overexpressing tumors was affected by the rate of metabolism and the route of administration.

Repetition of FDG PET study in the same day after appropriate patient preparation revealed two new cancer localizations: a case report

A positron emission tomography scan with fluorodeoxyglucose can be affected by several factors. Skeletal muscle activation and physiological presence of radioactivity in urine frequently cause difficulties in images interpretation. We report a case of a patient with a non-operable left lung cancer, who was scheduled for FDG PET examination for radiotherapy planning purposes. In the first scan performed in the morning both elevated muscular and urinary uptake were present. For this reason another examination was performed on the same day. A new dose of radiopharmaceutical was given five hours after the first FDG injection and the patient was instructed to drink a large quantity of water in the meantime. The second PET scan clearly revealed two new lesions not visible at the time of the first examination: a synchronous bladder cancer, previously not known, and a mediastinal metastasis of the primary lung cancer. This case emphasizes the importance of correct patient preparation and shows the possibility to repeat PET examination on the same day.

Imaging features of primary Sarcomas of the great vessels in CT, MRI and PET/CT: a single-center experience

BackgroundTo investigate the imaging features of primary sarcomas of the great vessels in CT, MRI and 18 F-FDG PET/CT.MethodsThirteen patients with a primary sarcoma of the great vessels were retrospectively evaluated. All available images studies including F-18 FDG PET(/CT) (n = 4), MDCT (n = 12) and MRI (n = 6) were evaluated and indicative image features of this rare tumor entity were identified.ResultsThe median interval between the first imaging study and the final diagnosis was 11 weeks (0–12 weeks). The most frequently observed imaging findings suggestive of malignant disease in patients with sarcomas of the pulmonary arteries were a large filling defect with vascular distension, unilaterality and a lack of improvement despite effective anticoagulation. In patients with aortic sarcomas we most frequently observed a pedunculated appearance and an atypical location of the filling defect. The F-18 FDG PET(/CT) examinations demonstrated an unequivocal hypermetabolism of the lesion in all cases (4/4). MRI proved lesion vascularization in 5/6 cases.ConclusionIntravascular unilateral or atypically located filling defects of the great vessels with vascular distension, a pedunculated shape and lack of improvement despite effective anticoagulation are suspicious for primary sarcoma on MDCT or MRI. MR perfusion techniques can add information on the nature of the lesion but the findings may be subtle and equivocal. F-18 FDG PET/CT may have a potential role in these patients and may be considered as part of the imaging workup.

Effect of a single dose of escitalopram on serotonin concentration in the non-human and human primate brain

Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for treatment of psychiatric disorders. The exact mechanism underlying the clinical effects of SSRIs remains unclear, although increased synaptic serotonin concentrations have been hypothesized to be an initial step. [¹¹C]AZ10419369 is a novel 5-HT(1B) receptor selective radioligand, which is sensitive to changes in endogenous serotonin concentrations. To assess whether a single dose of the SSRI escitalopram affects endogenous serotonin concentrations in serotonergic projection areas and in the raphe nuclei (RN), three cynomolgus monkeys and nine human subjects underwent PET examinations with [¹¹C]AZ10419369 at baseline conditions and after escitalopram administration. In monkeys, the binding potential (BP(ND)) was significantly lower post dose compared to baseline in dorsolateral prefrontal cortex, occipital cortex, thalamus, midbrain and RN (p < 0.05). In humans, the BP(ND) tended to decrease in RN post dose (p = 0.08). In all serotonergic projection areas, the BP(ND) was conversely higher post dose compared to baseline. The increase was significant in a combined region of all projection areas (p = 0.01) and in occipital and temporal cortex (p < 0.05). SSRIs are generally assumed to elevate endogenous serotonin concentrations in projection areas, evoking the antidepressant effect. In the present study, a single, clinically relevant, dose of escitalopram was found to decrease serotonin concentrations in serotonergic projection areas in humans. Hypothetically, desensitization of inhibitory serotonergic autoreceptors will cause the serotonin concentration in projection areas to increase over time with chronic administration. Thus, the findings in the present study might aid in understanding the mechanism of SSRIs' delayed onset of clinical effect.

18F]Fallypride: Metabolism studies and quantification of the radiotracer and its radiometabolites in plasma using a simple and rapid solid-phase extraction method

[(18)F]Fallypride, a fluorinated and substituted benzamide with high affinity for D2/D3 receptors, is a useful PET radioligand for the study of striatal/extrastriatal areas. Since [(18)F]fallypride is extensively metabolized in vivo and since PET examinations are long lasting in humans, the rapid measurement of the unchanged radiotracer in plasma is essential for the quantification of images. The present study aims: i) to evaluate if the radiometabolites of [(18)F]fallypride cross the blood-brain barrier in rodents, ii) to identify these radiometabolites in baboon plasma and iii) to develop a rapid solid phase extraction method (SPE) suitable for human applications to quantify both [(18)F]fallypride and its radiometabolites in plasma. The metabolites P450-dependant in rat and human liver microsomes were characterized by LC-MS-MS and compared to those detected in vivo. Sequential solvent elution on Oasis®-MCX-SPE cartridges was used to quantify [(18)F]fallypride and its radiometabolites. In rat microsomal incubations, five metabolites generated upon N/O-dealkylation or hydroxylation at the pyrrolidine and/or at the benzamide moiety were identified. No radiometabolite was detected in the rat brain. N-dealkylated and hydroxylated derivatives were detected in human microsomal incubations as well as in baboon plasma. The use of SPE (total recovery 100.2%± 2.8%, extraction yield 95.5%± 0.3%) allowed a complete separation of [(18)F]fallypride from its radiometabolites in plasma and evaluate [(18)F]fallypride at 150 min pi to be 22%± 5% of plasma radioactivity. The major in vivo radiometabolites of [(18)F]fallypride were produced by N-dealkylation and hydroxylation. Allowing the rapid analysis of multiple plasma samples, SPE is a method of choice for the determination of [(18)F]fallypride until late images required for quantitative PET imaging in humans.

Intramedullary Spinal Cord Metastases: Visibility on PET and Correlation with MRI Features

Studies systematically evaluating the detection of intramedullary spinal cord metastasis with PET are lacking. Our purpose was to evaluate the visibility of intramedullary spinal cord metastasis on PET in a single institutional series and to correlate PET and MR imaging features. Patients were included if pretreatment MR imaging identifying an intramedullary spinal cord metastasis and an [(18)F] FDG-PET examination near the time of MR imaging were available. PET examinations were retrospectively reviewed, with reviewers blinded and then unblinded to the PET report and MR imaging findings. PET intramedullary spinal cord metastasis features were compared with and correlated with previously analyzed MR imaging lesion characteristics. Original clinical PET reports were reviewed. The final study sample was 10 PET examinations in 10 patients with 13 intramedullary spinal cord metastases. In 7 (70%) patients, retrospective blinded review demonstrated convincing evidence of 10 (77%) intramedullary spinal cord metastases. Three MR imaging features correlated with intramedullary spinal cord metastases being visible on PET compared with those nonvisible, respectively: larger lesion enhancement size: mean size: 32.1 mm versus 6.0 mm (P = .038); larger longitudinal extent of T2 signal abnormality: mean 5.6 versus 1.0 segments (P = .0081); and larger ratio of extent of T2 signal abnormality to contrast enhancement: 3.8 versus 1.0 (P = .0069). Intramedullary spinal cord metastasis was confidently reported clinically in 2 (20%) patients, accounting for 5 (38%) intramedullary spinal cord metastases. Most intramedullary spinal cord metastases can be detected on PET when performed near the time of pretreatment MR imaging. However, intramedullary spinal cord metastases may not be clinically reported on PET. Larger lesions with more edema are more likely to be visible. The spinal cord should be specifically and carefully assessed on PET for evidence of intramedullary spinal cord metastases to provide timely diagnosis.

How do we define amyloid positivity in an asymptomatic population? Comparison of CSF, quantitative PET and clinical PET examinations

How do we define amyloid positivity in an asymptomatic population? Comparison of CSF, quantitative PET and clinical PET examinations

Ultrashort-acting insulin may improve on 18F-FDG PET/CT image quality in patients with uncontrolled diabetic mellitus

It is known that the poor image quality of (18)F-fluorodeoxyglucose ((18)F-FDG) PET scans leads to interpretation difficulty in patients with uncontrolled diabetes mellitus (DM). We usually delay (18)F-FDG PET examination when patients show high glucose levels. This study was performed to evaluate the usefulness and effects of ultrashort-acting insulin on (18)F-FDG PET/computed tomography (CT) imaging in DM patients. A total of 105 DM patients (68 men and 37 women) were included. Ultrashort-acting insulin was intravenously injected when patients showed high glucose levels (>190 mg/dl). (18)F-FDG was injected 60 min after ultrashort-acting insulin injection, and PET/CT images were acquired. Image quality was graded by consensus using the following scale: 1, good; 2, moderate; and 3, poor. The mean standardized uptake value (SUV(mean)) of the liver, gluteal muscle, and brain was assessed to evaluate the effects of ultrashort-acting insulin. The group administered ultrashort-acting insulin (n=52, blood glucose level: 243.7 ± 46.2 mg/dl) showed a significantly higher glucose level compared with the group not administered ultrashort-acting insulin (n=53, 177.1 ± 5.2 mg/dl). Nevertheless, the image quality of the group with ultrashort-acting insulin was not significantly different from that of the group without ultrashort-acting insulin (χ(2) -test, P=0.47). No significant differences were seen in SUV(mean) in the liver (P=0.13), gluteal muscle (P=0.71), and brain (P=0.16) between groups. Ultrashort-acting insulin can be used to improve the image quality of F-FDG PET/CT in uncontrolled DM patients without significant differences in SUV.

Brain β-amyloid load approaches a plateau

To model the temporal trajectory of β-amyloid accumulation using serial amyloid PET imaging. Participants, aged 70-92 years, were enrolled in either the Mayo Clinic Study of Aging (n = 246) or the Mayo Alzheimer's Disease Research Center (n = 14). All underwent 2 or more serial amyloid PET examinations. There were 205 participants classified as cognitively normal and 55 as cognitively impaired (47 mild cognitive impairment and 8 Alzheimer dementia). We measured baseline amyloid PET-relative standardized uptake values (SUVR) and, for each participant, estimated a slope representing their annual amyloid accumulation rate. We then fit regression models to predict the rate of amyloid accumulation given baseline amyloid SUVR, and evaluated age, sex, clinical group, and APOE as covariates. Finally, we integrated the amyloid accumulation rate vs baseline amyloid PET SUVR association to an amyloid PET SUVR vs time association. Rates of amyloid accumulation were low at low baseline SUVR. Rates increased to a maximum at baseline SUVR around 2.0, above which rates declined-reaching zero at baseline SUVR above 2.7. The rate of amyloid accumulation as a function of baseline SUVR had an inverted U shape. Integration produced a sigmoid curve relating amyloid PET SUVR to time. The average estimated time required to travel from an SUVR of 1.5-2.5 is approximately 15 years. This roughly 15-year interval where the slope of the amyloid SUVR vs time curve is greatest and roughly linear represents a large therapeutic window for secondary preventive interventions.

Fully automated deformable registration of breast DCE-MRI and PET/CT

Accurate characterization of breast tumors is important for the appropriate selection of therapy and monitoring of the response. For this purpose breast imaging and tissue biopsy are important aspects. In this study, a fully automated method for deformable registration of DCE-MRI and PET/CT of the breast is presented. The registration is performed using the CT component of the PET/CT and the pre-contrast T1-weighted non-fat suppressed MRI. Comparable patient setup protocols were used during the MRI and PET examinations in order to avoid having to make assumptions of biomedical properties of the breast during and after the application of chemotherapy. The registration uses a multi-resolution approach to speed up the process and to minimize the probability of converging to local minima. The validation was performed on 140 breasts (70 patients). From a total number of registration cases, 94.2% of the breasts were aligned within 4.0 mm accuracy (1 PET voxel). Fused information may be beneficial to obtain representative biopsy samples, which in turn will benefit the treatment of the patient.

Effects of a Ketogenic Diet on Brain Metabolism in Epilepsy

For a subpopulation of drug-resistant epilepsies, a ketogenic diet constitutes the treatment of choice. A ketogenic diet is a high-fat, low-protein, and low-carbohydrate diet, which induces ketosis. Despite the use in treatment of epilepsy since 1924, the clinical efficacy was not demonstrated in a controlled, randomized trial until 2008, showing its capability of reducing seizure frequency with more than 50%. However, the exact mechanism of this form of treatment is still unknown. We report here a patient with drug-resistant epilepsy on a ketogenic diet, where a brain 18F-FDG PET examination demonstrated a severely decreased uptake in the cerebral cortex bilaterally.

Discrimination and anatomical mapping of PET-positive lesions: comparison of CT attenuation-corrected PET images with coregistered MR and CT images in the abdomen

PET/MR has the potential to become a powerful tool in clinical oncological imaging. The purpose of this prospective study was to evaluate the performance of a single T1-weighted (T1w) fat-suppressed unenhanced MR pulse sequence of the abdomen in comparison with unenhanced low-dose CT images to characterize PET-positive lesions. A total of 100 oncological patients underwent sequential whole-body (18)F-FDG PET with CT-based attenuation correction (AC), 40mAs low-dose CT and two-point Dixon-based T1w 3D MRI of the abdomen in a trimodality PET/CT-MR system. PET-positive lesions were assessed by CT and MRI with regard to their anatomical location, conspicuity and additional relevant information for characterization. From among 66 patients with at least one PET-positive lesion, 147 lesions were evaluated. No significant difference between MRI and CT was found regarding anatomical lesion localization. The MR pulse sequence used performed significantly better than CT regarding conspicuity of liver lesions (p < 0.001, Wilcoxon signed ranks test), whereas no difference was noted for extrahepatic lesions. For overall lesion characterization, MRI was considered superior to CT in 40% of lesions, equal to CT in 49%, and inferior to CT in 11%. Fast Dixon-based T1w MRI outperformed low-dose CT in terms of conspicuity and characterization of PET-positive liver lesions and performed similarly in extrahepatic tumour manifestations. Hence, under the assumption that the technical issue of MR AC for whole-body PET examinations is solved, in abdominal PET/MR imaging the replacement of low-dose CT by a single Dixon-based MR pulse sequence for anatomical lesion correlation appears to be valid and robust.

18F]choline positron emission tomography in prostate cancer patients with biochemical recurrence after radical prostatectomy

Our purpose was to evaluate whether antiandrogen therapy (AAT) influences [(18)F]choline PET results in patients with biochemical recurrence after radical prostatectomy (RPE). Through a retrospective study we evaluated two groups of patients, both with histologically proven carcinoma of the prostate, who had undergone RPE and a subsequent [(18)F]choline PET because of biochemical failure (<4 ng/dl). One group consisted of 13 patients under AAT at the time of the PET examination (age range, 55-80 years; median, 68). The other group who had not undergone AAT consisted of 22 patients (age range, 48-72 years; median, 67). Our results were correlated with follow-up information related to histopathology, changes in prostate-specific antigen levels, other imaging modalities and clinical examination. Mean follow-up was 27 months. In patients who had undergone AAT, [(18)F]choline PET was true positive in eight out of 10 patients. The overall sensitivity in this group was 80%. In two cases [(18)F]choline PET turned out to be false negative, missing local relapse. Of the patients treated only with RPE, 10 out of 20 turned out to be true positive, resulting in a sensitivity of 50%.In all, in four patients biochemical recurrence could not be correlated to pathological findings in any of the available modalities. The difference in sensitivity between patients with and without AAT was statistically not significant (P=0.235). In patients with biochemical recurrence during AAT after RPE, [(18)F]choline PET can yield true-positive findings, even at prostate-specific antigen values of less than 4 ng/dl, and is an accurate technique for the detection of recurrence.

Prognostic value of the standardized uptake value for 18F-fluorodeoxyglucose in patients with stage IIIB melanoma

PurposeFDG PET/CT is an excellent tool to detect melanoma metastases and also allows quantification of FDG uptake using standardized uptake value (SUV). The aim of this study was to prospectively investigate the potential prognostic value of SUV for disease-free survival (DFS) and disease-specific survival (DSS) for patients with stage IIIB melanoma.MethodsFrom November 2003 to March 2008, all consecutive patients were included in the present study. Inclusion criteria were: palpable, histology- or cytology-proven lymph node metastases of melanoma, and referred to the University Medical Centre Groningen for FDG PET and CT examination. Patients without distant metastases were evaluated. Multivariable survival analysis was performed to determine whether SUV was associated with DFS and DSS (Cox proportional hazard analysis).ResultsIn 80 patients (without distant metastases, 65 %) SUV could be measured. Overall 5-year DFS was 41 % (95% CI 26–56 %) and 24 % (95% CI 12–38 %) in patients with a low and high SUVmean (p = 0.02), respectively. Overall 5-year DSS was 48 % (95% CI 31–62 %) and 30 % (95% CI 17–45 %) in patients with a low and high SUVmean (p = 0.04), respectively. In the multivariable analysis, SUVmean was associated with DFS (hazard ratio 1.7; p = 0.048), but was not associated with DSS (hazard ratio 1.6; p = 0.1). The number of positive nodes, extranodal growth and gender were also associated with survival.ConclusionFDG uptake in clinically overt nodal melanoma metastases is inversely associated with DFS. Univariate analysis showed an association with DSS. However, after adjustment for potential confounders this association was no longer significant. If these findings are confirmed in larger studies, SUVmean could potentially be used (in addition to the number of positive nodes, tumour size and extranodal growth) as a factor in deciding on adjuvant systemic treatment.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-012-2182-0) contains supplementary material, which is available to authorized users.

Adding 11C-acetate to 18F-FDG at PET Examination Has an Incremental Value in the Diagnosis of Hepatocellular Carcinoma

Objective: The sensitivity of FDG at PET examination of Hepatocellular Carcinoma (HCC) is restricted. In a few studies, all done in Oriental patients, PET-examination with 11C-acetate has shown a higher accuracy than with FDG. In the current study, the uptake of 11C-acetate has been compared with the uptake of FDG in the primary HCC in a cohort of Occidental patients. Material and Methods: 44 patients underwent PET-examination with both tracers with a mean of 9 days between the examinations. 26 patients had a microscopical diagnosis and 18 were diagnosed with multimodal radiological methods. At least one relevant radiological examination was available for comparison.Results: At visual evaluation, 13 of the HCC’s were positive at PET-examination using FDG and 34 were positive using 11C-acetate (p<0.001). Median tumor SUVmean of 11C-acetate was 4.7 and of FDG was 1.9 (p<0.001). There was also a higher uptake of 11C-acetate by the surrounding liver tissue than of FDG. Median liver SUVmean of [u]11[/u]C-acetate was 3.2 and of FDG it was 1.7 (p<0.001). This corresponded to a median tumour/liver tissue ratio for 11C-acetate of 1.4 and for FDG of 1.0 (p<0.05). Previous reports of a negative correlation between the uptake of the tracers were weakly supported. In 4 large tumors some portions being hot using one of the tracers were cold using the other tracer and vice versa.Conclusion: Adding registration with 11C-acetate to registration with FDG at PET-examination has an incremental value in the diagnosis of HCC. A higher tumor uptake of 11C-acetate cannot be taken full advantage of because of a higher uptake also by the surrounding liver tissue.Conflict of interest:None declared.

Reply

Downloaded from www.ajronline.org by UCLA Digital Coll SVCS on 05/06/15 from IP address 149.142.243.67. Copyright ARRS. For personal use only; all rights reserved Letters Reply Although Loizides et al. [1] read our ar- ticle [2] with “great interest and surprise,” we read their letter with shock. It appears that the writers have completely missed the objective of our article. Rather than create a laundry list of responses to the comments, we will address the two salient points that were obviously lost or overlooked. The objective of our article [2] was to “better elucidate factors that may contrib- ute to the success of CT-guided core needle biopsy.” The Results section addresses this very clearly. The purpose was not to com- pare different guidance techniques to deter- mine a “modality of choice.” This article was not designed to evaluate different imaging techniques for the diagno- sis of bone and soft-tissue tumors. It addresses CT as a tool for guiding biopsy. Our patients generally present with multiple outside studies, including radiography, MRI, ultrasound, radio- nuclide, and even PET examinations. Such fea- tures as necrosis, aggressive-appearing bone destruction, and vascularity are noted on these outside studies, and localization is transferred to unenhanced CT to target the area for tissue sampling. Admittedly, the legend for Figure 1 is somewhat misleading in alluding that CT was the only imaging tool available. We regret that our article [2] caused so much confusion for Loizides et al. [1]. Leanne L. Seeger Kambiz Motamedi David Geffen School of Medicine at UCLA, Los Angeles, CA; Scott D. Nelson Santa Monica–UCLA Medical Center, Santa Monica, CA DOI:10.2214/AJR.11.7865 WEB—This is a Web exclusive article.

Validation for performing 11C-methionine and 18F-FDG-PET studies on the same day

The performance of two PET examinations, one using L-[methyl-¹¹C] methionine (MET) and one using 2-[¹⁸F] fluoro-2-deoxy-D-glucose (FDG), on the same day may offer a clinical advantage for the investigation of brain tumors or other lesions. The purpose of this study was to investigate the effect of positron cross-talk (PCT) and to determine the optimal protocol for using MET and FDG on the same day. The participants comprised 62 patients with head and neck cancer. We focused on the high physiological uptake of MET in the liver and evaluated the effect of PCT with MET on FDG uptake in the liver and muscle. Three FDG-PET scans [one: whole body (early image), two: head and neck, and three: one-bed-position scan of the liver (delayed image)] were performed after completing a MET-PET scan (head and neck) at varying injection intervals. Standard uptake value mean variations in the liver and muscle were calculated, assuming that the differences between the early and the delayed images reflected the PCT from carbon-11 on fluorine-18, on the basis of the results of a phantom study and a study in volunteers. The participants were categorized into four groups (G) according to the injection interval: G1 (n=15, 30-49 min), G2 (n=16, 50-69 min), G3 (n=17, 70-89 min), and G4 (n=14, ≥ 90 min). The PCT level decreased from the G1 group through to the G3 group (analysis of variance, P<0.001) but was stable, with no further decrease in the G4 group. The PCT level in the muscle was not significantly different among the G1, G2, G3, and G4 groups (analysis of variance, P=0.693). Thus, PCT in the liver decreased at longer injection intervals, and PCT was no longer observed at injection intervals of more than 90 min. MET and FDG-PET examinations can be successfully performed on the same day without PCT between the studies if the injection interval is longer than 90 min. This method reduces the examination burden of patients and may be useful for performing multiple PET examinations while the patient's condition remains almost the same.

Clinical Validation of 18F-AZD4694, an Amyloid-β–Specific PET Radioligand

Pioneered with the invention of (11)C-Pittsburgh compound B, amyloid-β imaging using PET has facilitated research in Alzheimer disease (AD). This imaging approach has promise for diagnostic purposes and evaluation of disease-modifying therapies. Broad clinical use requires an (18)F-labeled amyloid-β radioligand with high specific and low nonspecific binding. The aim of the present PET study was to examine the radioligand (18)F-AZD4694 in human subjects. Six control subjects and 10 clinically diagnosed AD patients underwent PET examination with (18)F-AZD4694 and a structural MRI scan. Of these, 4 controls and 4 patients underwent a second PET examination for test-retest analysis. Arterial sampling was done to derive a metabolite-corrected plasma input function for traditional compartment modeling. Besides, several simplified quantitative approaches were applied, including the reference Logan approach and simple ratio methods. After intravenous injection of (18)F-AZD4694, radioactivity appeared rapidly in brain. In patients, radioactivity was high in regions expected to contain amyloid-β, whereas in controls, radioactivity was low and homogenously distributed. Binding in cerebellum, a reference region, was low and similar between the groups. Specific binding was reversible and peaked at about 27 min after injection in regions with high radioactivity. The time-activity curves could be described using the 2-tissue-compartment model. Distribution volume ratio estimates obtained using compartment models and simplified methods were highly correlated. Standardized uptake value ratios calculated at late times and distribution volume ratios estimated with the reference Logan approach were, in gray matter, significantly lower in control subjects (1.08 [11%] and 1.01 [6%], respectively) than in AD patients (2.15 [24%] and 1.62 [18%], respectively). Among noninvasive methods, the lowest test-retest variability was found with reference Logan, varying between 4% and 6% across brain regions. Noninvasive quantitative approaches provide valid estimates of amyloid-β binding. Because of the radioisotope ((18)F) used for labeling, the radioligand has potential for wide clinical application. (18)F-AZD4694 satisfies the requirements for a promising amyloid-β radioligand both for diagnostic use and for evaluation of disease-modifying therapies in AD.

Is There an Optimal Scan Time for 6-[F-18]Fluoro-L-DOPA PET in Pheochromocytomas and Paragangliomas?

To define the appropriate scan time for fluorine-18-labeled dihydroxyphenylalanine (F-18 DOPA) PET in oncological imaging of pheochromocytomas and paragangliomas. F-18 DOPA PET examinations were performed in 9 patients with 7 pheochromocytomas and 4 head and neck paragangliomas using a dedicated PET scanner. The acquisition started with a dynamic single-bed scan in the tumor region over the first 60 minutes after tracer injection followed by a late time whole-body scan at approximately 130 minutes. Standard uptake values (SUVs) were calculated in tumors, surrounding background, and adjacent normal tissues of relevance. Furthermore, kinetic analysis was performed using a 2-compartment model with rate constants for uptake (K1'), release (k2'), metabolism (k3'), and reverse reaction (k4') for region of interest and pixel-wise analysis. All tumors show a marked increased F-18 DOPA uptake, which was visually detectable and distinguishable from the surrounding tissue. The SUV is significantly lower in neck paraganglioma compared with abdominal pheochromocytomas. Mean time-activity curves of F-18 DOPA in tumors show a rapid uptake of the tracer. Already 2 minutes after the injection, the activity in the tumor is beyond that of the blood pool. The average maximum value (SUVmean = 8.2) has already been reached after 20 minutes. Afterward, a very slight decrease of the tumor SUV starts, which still amounts to 80% of the maximum value after 132 minutes. Due to the continuous decrease of activity in the background tissue, the tumor-to-background ratio of SUVs shows a constant increase within the entire period of examination. The mean values of apparent kinetic constants obtained by region of interest analysis averaged over all tumors are as follows: K1' = 2.89 ± 2.56 min(-1), k2' = 2.59 ± 2.81 min(-1), k3' = 0.301 ± 0.395 min(-1), and k4' = 0.044 ± 0.043 min(-1). Pheochromocytoma and paraganglioma take up F-18 DOPA very quickly. At best, the acquisition for static clinical PET imaging of paraganglioma with F-18 DOPA can start at 20 minutes postinjection for maximum uptake in tumors. Separation of tumor, background, and adjacent normal tissues is feasible due to their differences in SUV values and kinetics. The kinetic analysis demonstrates an F-18 DOPA accumulation within the tumor due to considerable differences between the rate constants of uptake and metabolism. Second, in contradiction to healthy brain, paraganglionic tumors show a reversible F-18 DOPA metabolism.

PET Imaging of Estrogen Receptors as a Diagnostic Tool for Breast Cancer Patients Presenting with a Clinical Dilemma

16α-(18)F-fluoro-17β-estradiol ((18)F-FES) is an estrogen receptor (ER)-specific PET tracer with various potential interesting applications. The precise contribution of this technique in current clinical practice, however, has yet to be determined. Therefore, the aim of this study was to evaluate the value of (18)F-FES PET in breast cancer patients presenting with a clinical dilemma. (18)F-FES PET examination could be requested by referring physicians for patients with a history of ER-positive breast cancer and the presence of a clinical dilemma despite complete standard work-up. All requests for (18)F-FES PET required a positive arbitration by a dedicated medical oncologist and nuclear medicine physician. The referring physician was asked to fill in validated questionnaires before, shortly after, and at more than 3 mo after (18)F-FES PET to determine indication, diagnostic value, and therapeutic consequences of (18)F-FES PET. To further validate (18)F-FES PET findings, (18)F-FES PET lesions were quantified and compared with centrally reviewed conventional imaging. Thirty-three patients underwent (18)F-FES PET between December 2008 and October 2010. (18)F-FES PET was requested to evaluate equivocal lesions on conventional work-up (n = 21), ER status in metastatic patients (n = 10), and the origin of metastases (n = 2). (18)F-FES-positive lesions were observed in 22 patients. (18)F-FES PET was especially sensitive for bone metastases, detecting 341 bone lesions, compared with 246 by conventional imaging. The sensitivity for liver metastases was poor, and quantification of (18)F-FES uptake in liver lesions was hampered by high physiologic background. (18)F-FES uptake was highly variable between all metastases (range of standardized uptake value, 1.20-18.81), and 45% of the patients with a positive (18)F-FES PET finding had both (18)F-FES-positive and (18)F-FES-negative metastases. (18)F-FES PET improved diagnostic understanding in 88% of the patients and led to therapy change in 48% of the patients. With the exception of liver metastases, whole-body imaging of ER expression with (18)F-FES PET can be a valuable additional diagnostic tool when standard work-up is inconclusive. (18)F-FES PET supported therapy decisions by improving diagnostic understanding and providing information on ER status of tumor lesions.