Jonathon A. Nye

Detection of Recurrent Prostate Carcinoma with anti-1-Amino-3-18F-Fluorocyclobutane-1-Carboxylic Acid PET/CT and 111In–Capromab Pendetide SPECT/CT

PURPOSE To compare the diagnostic performance of the synthetic amino acid analog radiotracer anti-1-amino-3-fluorine 18-fluorocyclobutane-1-carboxylic acid (anti-3-(18)F-FACBC) with that of indium 111 ((111)In)-capromab pendetide in the detection of recurrent prostate carcinoma. MATERIALS AND METHODS This prospective study was approved by the institutional review board and complied with HIPAA guidelines. Written informed consent was obtained. Fifty patients (mean age, 68.3 years ± 8.1 [standard deviation]; age range, 50-90 years) were included in the study on the basis of the following criteria: (a) Recurrence of prostate carcinoma was suspected after definitive therapy for localized disease, (b) bone scans were negative, and (c) anti-3-(18)F-FACBC positron emission tomography (PET)/computed tomography (CT) and (111)In-capromab pendetide single photon emission computed tomography (SPECT)/CT were performed within 6 weeks of each other. Studies were evaluated by two experienced interpreters for abnormal uptake suspicious for recurrent disease in the prostate bed and extraprostatic locations. The reference standard was a combination of tissue correlation, imaging, laboratory, and clinical data. Diagnostic performance measures were calculated and tests of the statistical significance of differences determined by using the McNemar χ(2) test as well as approximate tests based on the difference between two proportions. RESULTS For disease detection in the prostate bed, anti-3-(18)F-FACBC had a sensitivity of 89% (32 of 36 patients; 95% confidence interval [CI]: 74%, 97%), specificity of 67% (eight of 12 patients; 95% CI: 35%, 90%), and accuracy of 83% (40 of 48 patients; 95% CI: 70%, 93%). (111)In-capromab pendetide had a sensitivity of 69% (25 of 36 patients; 95% CI: 52%, 84%), specificity of 58% (seven of 12 patients; 95% CI: 28%, 85%), and accuracy of 67% (32 of 48 patients; 95% CI: 52%, 80%). In the detection of extraprostatic recurrence, anti-3-(18)F-FACBC had a sensitivity of 100% (10 of 10 patients; 95% CI: 69%, 100%), specificity of 100% (seven of seven patients; 95% CI: 59%, 100%), and accuracy of 100% (17 of 17 patients; 95% CI: 80%, 100%). (111)In-capromab pendetide had a sensitivity of 10% (one of 10 patients; 95% CI: 0%, 45%), specificity of 100% (seven of seven patients; 95% CI: 59%, 100%), and accuracy of 47% (eight of 17 patients; 95% CI: 23%, 72%). CONCLUSION anti-3-(18)F-FACBC PET/CT was more sensitive than (111)In-capromab pendetide SPECT/CT in the detection of recurrent prostate carcinoma and is highly accurate in the differentiation of prostatic from extraprostatic disease. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11102023/-/DC1.

MR‐based attenuation correction for hybrid PET‐MR brain imaging systems using deformable image registration

PURPOSE Realization of combined positron emission tomography (PET)--magnetic resonance (MR) scanners has the potential to significantly change healthcare and revolutionize clinical practice as it allows, simultaneously, visualization of molecular imaging and anatomical imaging. PET-MR, acquired in one imaging study, will likely become the advanced imaging modality of choice for neurological studies, certain forms of cancer, stroke, and the emerging study of stem cell therapy. A challenge toward the implementation and operation of combined PET-MR scanners is that attenuation corrections maps are not directly available due to space and cost constraints. This article presents a method to obtain accurate patient-specific PET attenuation coefficients maps in head imaging by warping an atlas computed tomography (CT) data set to the patient-specific MR data set using a deformable registration model. METHODS A multimodality optical flow deformable model has been developed that establishes a voxel-to-voxel correspondence between the CT atlas and patient MR images. Once the mapping is established, the atlas is warped with the deformation field obtained by the registration to create a simulated CT image study that matches the patient anatomy, which could be used for attenuation correction. RESULTS To evaluate the accuracy of the deformable-based attenuation correction, 17 clinical brain tumor cases were studied using acquired MR-CT images. A simulated CT was compared to the patients true CT to assess geometrical accuracy of the deformation module as well as voxel-to-voxel comparison of Hounsfield units (HUs). In all cases, mapping from the atlas CT to the individual MR was achieved with geometrical accuracy as judged using quantitative inspection tools. The mean distance between simulated and true CT external contour and bony anatomy was 1.26 and 2.15 mm, respectively. In terms of HU unit comparison, the mean voxel-to-voxel difference was less than 2 HU for all cases. CONCLUSIONS Attenuation correction for hybrid PET-MR scanners was easily achieved by individualizing an atlas CT to the MR data set using a deformable model without requiring user interaction. The method provided clinical accuracy while eliminating the need for an additional CT scan for PET attenuation correction.

Chronic Interferon- α Decreases Dopamine 2 Receptor Binding and Striatal Dopamine Release in Association with Anhedonia-Like Behavior in Nonhuman Primates

Neuroimaging studies in humans have demonstrated that inflammatory cytokines target basal ganglia function and presynaptic dopamine (DA), leading to symptoms of depression. Cytokine-treated nonhuman primates also exhibit evidence of altered DA metabolism in association with depressive-like behaviors. To further examine cytokine effects on striatal DA function, eight rhesus monkeys (four male, four female) were administered interferon (IFN)-α (20 MIU/m2 s.c.) or saline for 4 weeks. In vivo microdialysis was used to investigate IFN-α effects on DA release in the striatum. In addition, positron emission tomography (PET) with [11C]raclopride was used to examine IFN-α-induced changes in DA2 receptor (D2R) binding potential before and after intravenous amphetamine administration. DA transporter binding was measured by PET using [18F]2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane. Anhedonia-like behavior (sucrose consumption) was assessed during saline and IFN-α administration. In vivo microdialysis demonstrated decreased release of DA after 4 weeks of IFN-α administration compared with saline. PET neuroimaging also revealed decreased DA release after 4 weeks of IFN-α as evidenced by reduced displacement of [11C]raclopride following amphetamine administration. In addition, 4 weeks of IFN-α was associated with decreased D2R binding but no change in the DA transporter. Sucrose consumption was reduced during IFN-α administration and was correlated with decreased DA release at 4 weeks as measured by in vivo microdialysis. Taken together, these findings indicate that chronic peripheral IFN-α exposure reduces striatal DA release in association with anhedonia-like behavior in nonhuman primates. Future studies examining the mechanisms of cytokine effects on DA release and potential therapeutic strategies to reverse these changes are warranted.

Anti-3-[18F]FACBC Positron Emission Tomography-Computerized Tomography and 111In-Capromab Pendetide Single Photon Emission Computerized Tomography-Computerized Tomography for Recurrent Prostate Carcinoma: Results of a Prospective Clinical Trial

PURPOSE We prospectively evaluated the amino acid analogue positron emission tomography radiotracer anti-3-[(18)F]FACBC compared to ProstaScint® ((111)In-capromab pendetide) single photon emission computerized tomography-computerized tomography to detect recurrent prostate carcinoma. MATERIALS AND METHODS A total of 93 patients met study inclusion criteria who underwent anti-3-[(18)F]FACBC positron emission tomography-computerized tomography plus (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for suspected recurrent prostate carcinoma within 90 days. Reference standards were applied by a multidisciplinary board. We calculated diagnostic performance for detecting disease. RESULTS In the 91 of 93 patients with sufficient data for a consensus on the presence or absence of prostate/bed disease anti-3-[(18)F]FACBC had 90.2% sensitivity, 40.0% specificity, 73.6% accuracy, 75.3% positive predictive value and 66.7% negative predictive value compared to (111)In-capromab pendetide with 67.2%, 56.7%, 63.7%, 75.9% and 45.9%, respectively. In the 70 of 93 patients with a consensus on the presence or absence of extraprostatic disease anti-3-[(18)F]FACBC had 55.0% sensitivity, 96.7% specificity, 72.9% accuracy, 95.7% positive predictive value and 61.7% negative predictive value compared to (111)In-capromab pendetide with 10.0%, 86.7%, 42.9%, 50.0% and 41.9%, respectively. Of 77 index lesions used to prove positivity histological proof was obtained in 74 (96.1%). Anti-3-[(18)F]FACBC identified 14 more positive prostate bed recurrences (55 vs 41) and 18 more patients with extraprostatic involvement (22 vs 4). Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography correctly up-staged 18 of 70 cases (25.7%) in which there was a consensus on the presence or absence of extraprostatic involvement. CONCLUSIONS Better diagnostic performance was noted for anti-3-[(18)F]FACBC positron emission tomography-computerized tomography than for (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for prostate carcinoma recurrence. The former method detected significantly more prostatic and extraprostatic disease.

Biodistribution and Radiation Dosimetry of the Synthetic Nonmetabolized Amino Acid Analogue Anti-18F-FACBC in Humans

The synthetic leucine amino acid analog anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid (anti-18F-FACBC) is a recently developed ligand that permits the evaluation of the L-amino acid transport system. This study evaluated the whole-body radiation burden of anti-18F-FACBC in humans. Methods: Serial whole-body PET/CT scans of 6 healthy volunteers (3 male and 3 female) were acquired for 2 h after a bolus injection of anti-18F-FACBC (366 ± 51 MBq). Organ-specific time–activity curves were extracted from the reconstructed data and integrated to evaluate the individual organ residence times. A uniform activity distribution was assumed in the body organs with urine collection after the study. Estimates of radiation burden to the human body were calculated on the basis of the recommendations of the MIRD committee. The updated dynamic bladder model was used to calculate dose to the bladder wall. Results: All volunteers showed initially high uptake in the pancreas and liver, followed by rapid clearance. Skeletal muscle and bone marrow showed lower and prolonged uptake, with clearance dominated by the tracer half-life. The liver was the critical organ, with a mean absorbed dose of 52.2 μGy/MBq. The estimated effective dose was 14.1 μSv/MBq, representing less than 20% of the dose limit recommended by the Radioactive Drug Research Committee for a 370-MBq injection. Bladder excretion was low and initially observed 6 min after injection, well after peak tracer uptake in the body organs. Conclusion: The PET whole-body dosimetry estimates indicate that an approximately 370-MBq injection of anti-18F-FACBC yields good imaging and acceptable dosimetry. The nonmetabolized nature of this tracer is favorable for extraction of relevant physiologic parameters from kinetic models.

Minimizing artifacts resulting from respiratory and cardiac motion by optimization of the transmission scan in cardiac PET/CT

The introduction of positron emission/computed tomography (PET/CT) systems coupled with multidetector CT arrays has greatly increased the amount of clinical information in myocardial perfusion studies. The CT acquisition serves the dual role of providing high spatial anatomical detail and attenuation correction for PET. However, the differences between the interaction of respiratory and cardiac cycles in the CT and PET acquisitions presents a challenge when using the CT to determine PET attenuation correction. Three CT attenuation correction protocols were tested for their ability to produce accurate emission images: gated, a step mode acquisition covering the diastolic heart phase; normal, a high-pitch helical CT; and slow, a low-pitch, low-temporal-resolution helical CT. The amount of cardiac tissue in the emission image that overlaid lung tissue in the transmission image was used as the measure of mismatch between acquisitions. Phantom studies simulating misalignment of the heart between the transmission and emission sequences were used to correlate the amount of mismatch with the artificial defect changes in the emission image. Consecutive patients were studied prospectively with either paired gated (diastolic phase, 120 kVp, 280 mA, 2.6 s) and slow CT (0.562:1 pitch, 120 kVp, Auto-mA, 16 s) or paired normal (0.938:1 pitch, 120 kVp, Auto-mA, 4.8 s) and slow CT protocols, prior to a Rb-82 perfusion study. To determine the amount of mismatch, the transmission and emission images were converted to binary representations of attenuating tissue and cardiac tissue and overlaid using their native registration. The number of cardiac tissue pixels from the emission image present in the CT lung field yielded the magnitude of misalignment represented in terms of volume, of where a small volume indicates better registration. Acquiring a slow CT improved registration between the transmission and emission acquisitions compared to the gated and normal CT protocols. The volume of PET cardiac tissue in the CT lung field was significantly lower (p < 0.03) for the slow CT protocol in both the rest and stress emission studies. Phantom studies showed that an overlaying volume greater than 2.6 mL would produce significant artificial defects as determined by a quantitative software package that employs a normal database. The percentage of patient studies with overlaying volume greater than 2.6 mL was reduced from 71% with the normal CT protocol to 28% with the slow CT protocol. The remaining 28% exhibited artifacts consistent with heart drift and patient motion that could not be corrected by adjusting the CT acquisition protocol. The low pitch of the slow CT protocol provided the best match to the emission study and is recommended for attenuation correction in cardiac PET/CT studies. Further reduction in artifacts arising from cardiac drift is required and warrants an image registration solution.

Sex differences in mental stress-induced myocardial ischemia in young survivors of an acute myocardial infarction.

Objectives Emotional stress may disproportionally affect young women with ischemic heart disease. We sought to examine whether mental stress–induced myocardial ischemia (MSIMI), but not exercise-induced ischemia, is more common in young women with previous myocardial infarction (MI) than in men. Methods We studied 98 post-MI patients (49 women and 49 men) aged 38 to 60 years. Women and men were matched for age, MI type, and months since MI. Patients underwent technetium-99m sestamibi perfusion imaging at rest, after mental stress, and after exercise/pharmacological stress. Perfusion defect scores were obtained with observer-independent software. A summed difference score (SDS), the difference between stress and rest scores, was used to quantify ischemia under both stress conditions. Results Women 50 years or younger, but not older women, showed a more adverse psychosocial profile than did age-matched men but did not differ for conventional risk factors and tended to have less angiographic coronary artery disease. Compared with age-matched men, women 50 years or younger exhibited a higher SDS with mental stress (3.1 versus 1.5, p = .029) and had twice the rate of MSIMI (SDS ≥3; 52% versus 25%), whereas ischemia with physical stress did not differ (36% versus 25%). In older patients, there were no sex differences in MSIMI. The higher prevalence of MSIMI in young women persisted when adjusting for sociodemographic and life-style factors, coronary artery disease severity, and depression. Conclusions MSIMI post-MI is more common in women 50 years or younger compared with age-matched men. These sex differences are not observed in post-MI patients who are older than 50 years.

MR/PET quantification tools: Registration, segmentation, classification, and MR-based attenuation correction

PURPOSE Combined MR∕PET is a relatively new, hybrid imaging modality. A human MR∕PET prototype system consisting of a Siemens 3T Trio MR and brain PET insert was installed and tested at our institution. Its present design does not offer measured attenuation correction (AC) using traditional transmission imaging. This study is the development of quantification tools including MR-based AC for quantification in combined MR∕PET for brain imaging. METHODS The developed quantification tools include image registration, segmentation, classification, and MR-based AC. These components were integrated into a single scheme for processing MR∕PET data. The segmentation method is multiscale and based on the Radon transform of brain MR images. It was developed to segment the skull on T1-weighted MR images. A modified fuzzy C-means classification scheme was developed to classify brain tissue into gray matter, white matter, and cerebrospinal fluid. Classified tissue is assigned an attenuation coefficient so that AC factors can be generated. PET emission data are then reconstructed using a three-dimensional ordered sets expectation maximization method with the MR-based AC map. Ten subjects had separate MR and PET scans. The PET with [(11)C]PIB was acquired using a high-resolution research tomography (HRRT) PET. MR-based AC was compared with transmission (TX)-based AC on the HRRT. Seventeen volumes of interest were drawn manually on each subject image to compare the PET activities between the MR-based and TX-based AC methods. RESULTS For skull segmentation, the overlap ratio between our segmented results and the ground truth is 85.2 ± 2.6%. Attenuation correction results from the ten subjects show that the difference between the MR and TX-based methods was <6.5%. CONCLUSIONS MR-based AC compared favorably with conventional transmission-based AC. Quantitative tools including registration, segmentation, classification, and MR-based AC have been developed for use in combined MR∕PET.

Anti-1-Amino-3-18F-Fluorocyclobutane-1-Carboxylic Acid: Physiologic Uptake Patterns, Incidental Findings, and Variants That May Simulate Disease

Anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid (18F-FACBC) is a synthetic amino acid analog PET radiotracer undergoing clinical trials for the evaluation of prostate and other cancers. We aimed to describe common physiologic uptake patterns, incidental findings, and variants in patients who had undergone 18F-FACBC PET. Methods: Sixteen clinical trials involving 611 18F-FACBC studies from 6 centers, which included dosimetry studies on 12 healthy volunteers, were reviewed. Qualitative observations of common physiologic patterns, incidental uptake, and variants that could simulate disease were recorded and compared with similar observations in studies of the healthy volunteers. Quantitative analysis of select data and review of prior published reports and observations were also made. Results: The liver and pancreas demonstrated the most intense uptake. Moderate salivary and pituitary uptake and variable mild to moderate bowel activity were commonly visualized. Moderate bone marrow and mild muscle activity were present on early images, with marrow activity decreasing and muscle activity increasing with time. Brain and lungs demonstrated activity less than blood pool. Though 18F-FACBC exhibited little renal excretion or bladder uptake during the clinically useful early imaging time window, mild to moderate activity might accumulate in the bladder and interfere with evaluation of adjacent prostate bed and seminal vesicles in 5%–10% of patients. Uptake might also occur from benign processes such as infection, inflammation, prostatic hyperplasia, and metabolically active benign bone lesions such as osteoid osteoma. Conclusion: Common physiologic uptake patterns were similar to those noted in healthy volunteers. The activity in organs followed the presence of amino acid transport and metabolism described with other amino acid–based PET radiotracers. As with other PET radiotracers such as 18F-FDG, focal nonphysiologic uptake may represent incidental malignancy. Uptake due to benign etiologies distinct from physiologic background also occurred and could lead to misinterpretations if the reader is unaware of them.

Absent coronary artery calcium excludes inducible myocardial ischemia on computed tomography/positron emission tomography.

OBJECTIVE We set out to determine whether a coronary artery calcium (CAC) score of zero on computed tomography (CT) would predict a normal myocardial perfusion positron emission tomography (PET) in a population mostly at intermediate pretest likelihood of coronary artery disease (CAD). METHODS We enrolled 206 outpatients (36% men, mean age 60 ± 13 years) referred for Rb-82 myocardial perfusion PET/CT for suspected CAD. CAC scoring was performed by the Agatston method. The PET images were scored on a 5-point scale using a 17-segment left ventricular model. A summed stress score ≥ 2 was considered abnormal. Multivariable logistic regression analysis was used to test the independent predictive value of a CAC score of zero to exclude inducible myocardial ischemia. RESULTS Ninety-nine of 206 patients (48%) had a CAC score of zero and of these only 1 had inducible ischemia on PET. This yielded a negative predictive value of 99% (95% CI 95%-100%). CAC score of zero was the strongest independent predictor of a normal myocardial perfusion PET (OR = 0.05; 95% CI = 0.006-0.38; p = 0.004). CONCLUSION In a population of predominately intermediate likelihood of CAD, a CAC score of zero excludes inducible ischemia on myocardial perfusion PET.