Bennett B. Chin

111In oxine labelled mesenchymal stem cell SPECT after intravenous administration in myocardial infarction

Mesenchymal stem cells (MSCs) have shown therapeutic potential if successfully delivered to the intended site of myocardial infarction. The purpose of this pilot study was to test the feasibility of 111In oxine labelling of MSCs and single photon emission computed tomography (SPECT) imaging after intravenous administration in a porcine model of myocardial infarction. Adult farm pigs (n = 2) were subjected to closed chest experimental myocardial infarction. 111In oxine labelled MSCs (1×107 to 2×107 cells) were infused intravenously, and SPECT imaging was performed initially and on days 1, 2, 7 and 14. High quality SPECT images were obtained through 2 weeks of imaging. High initial MSC localization occurred in the lungs and slow progressive accumulation occurred in the liver, spleen and bone marrow. Renal activity was mild and persistent throughout imaging. No appreciable accumulation occurred in the myocardium. It is concluded that 111In oxine radiolabelling of MSCs is feasible, and in vivo imaging with SPECT provides a non-invasive method for sequentially monitoring cell trafficking with good spatial resolution. Because intravenous administration of MSCs results in significant lung activity that obscures the assessment of myocardial cell trafficking, alternative routes of administration should be investigated for this application.

Molecular imaging of small animals with a triple-head SPECT system using pinhole collimation

Pinhole collimation yields high sensitivity when the distance from the object to the aperture is small, as in the case of imaging small animals. Fine-resolution images may be obtained when the magnification is large since this mitigates the effect of detector resolution. Large magnifications in pinhole single-photon emission computed tomography (SPECT) may be obtained by using a collimator whose focal length is many times the radius of rotation. This may be achieved without truncation if the gamma camera is large. We describe a commercially available clinical scanner mated with pinhole collimation and an external linear stage. The pinhole collimation gives high magnification. The linear stage allows for helical pinhole SPECT. We have used the system to image radiolabeled molecules in phantoms and small animals.

The value of a baseline bone scan in patients with newly diagnosed prostate cancer.

PURPOSE This study evaluated the role of bone scans in managing newly diagnosed, untreated prostate cancer. METHODS Two hundred seventy consecutive staging bone scans in patients (mean age, 69 years) with newly diagnosed prostate cancer who had serum prostate-specific antigen (PSA) determinations and biopsies between January 1995 and October 1997 were evaluated retrospectively. RESULTS The bone scans were positive for metastatic bone disease in 24 patients and negative in 246. Serum PSA levels, the number of positive biopsy cores, the extent of tumor in the prostate gland, and Gleason scores were all significantly correlated with scintigraphic bone metastases (P < 0.0001 for each). Of the 177 patients with PSA levels less than 10 ng/ml, three had bone metastases. Bone metastases were found in 2 of 34 patients with PSA levels of 10.1 to 20 ng/ml, in 3 of 29 patients with PSA values of 20.1 to 50 ng/ml, and in 16 of 30 patients with PSA levels greater than 50.1 ng/ml. Only one patient had a bone metastasis when the prostate cancer involved fewer than 2 biopsy cores (1 of 135) or when disease was confined to one lobe (1 of 131), but the incidence increased significantly when the malignancy involved three or more biopsy cores (20 of 114) or disease was present in both prostate lobes (20 of 118). Four of 160 patients with Gleason scores less than 6 had bone metastases, whereas 20 of 110 patients with Gleason scores greater than 7 had bone metastases. CONCLUSIONS The likelihood of bone metastases is low in patients with newly diagnosed, untreated prostate cancer when the initial PSA level was less than 10 ng/ml, the number of positive biopsy cores was less than 2, tumor was confined to one lobe, or the Gleason score was less than 6. However, none of these criteria can be used to exclude metastatic bone disease. A baseline bone scan is an important staging procedure and should be obtained to provide maximum data for clinical management of the disease.

Anatomical loci of HIV-associated immune activation and association with viraemia

BACKGROUND Lymphocyte activation, associated with vaccination or infection, can be measured by positron emission tomography (PET). We investigated the ability of PET to detect and measure magnitude of lymph-node activation among asymptomatic HIV-1-infected individuals. METHODS Initially we assessed PET response in eight HIV-1-uninfected individuals who had received licensed killed influenza vaccine. In an urban teaching hospital, we recruited 12 patients recently infected with HIV-1 (<18 months since seroconversion) and 11 chronic long-term HIV-1 patients who had stable viraemia by RT-PCR (non-progressors). After injection with fluorine-18-labelled fluorodeoxyglucose, patients underwent PET. We correlated summed PET signal from nodes with viral load by linear regression on log-transformed values. FINDINGS Node activation was more localised after vaccination than after HIV-1 infection. In early and chronic HIV-1 disease, node activation was greater in cervical and axillary than in inguinal and iliac chains (p<0.0001), and summed PET signal correlated with viraemia across a 4 log range (r2=0.98, p<0.0001). Non-progressors had small numbers of persistently active nodes, most of which were surgically accessible. INTERPRETATION The anatomical restriction we noted may reflect microenvironmental niche selection, and tight correlation of PET signal with viraemia suggests target-cell activation determines steady-state viral replication.

PET/CT: artifacts caused by bowel motion.

Background and aimIn a combined positron emission tomography (PET) and computed tomography (CT) system, the CT images can be used for attenuation correction as well as for image fusion. However, quantitative and qualitative differences have been reported between CT based attenuation corrected PET and conventional transmission scan corrected PET images. The purpose of this study was to investigate potential differences in PET/CT caused by attenuation differences in bowel due to motion. MethodsTwelve patients had PET/CT scans performed using 68Ge transmission and CT attenuation correction methods. Three emission imaging datasets were generated including CT corrected PET, Ge corrected PET, and the difference images (CT corrected PET minus Ge corrected PET). PET difference images were used to identify regions of mismatch and to quantify possible discordance between images by using standardized uptake values (SUVs). Using the Ge corrected PET as the standard, differences in emission images were classified as an overestimation (pattern A) or an underestimation (pattern B) in these difference images. ResultsOne hundred and twenty-three mismatched areas were identified. Among them, overestimated areas in CT corrected image were detected in 36 regions (pattern A), while underestimated areas were evaluated in the remaining 87 regions (pattern B). The mean value of the difference in pattern A (mean±standard deviation=0.84±0.44) was slightly higher than that in pattern B (0.60±0.23), and statistically significant. Six of 36 regions in pattern A had an SUV of greater than 2.5 in CT corrected PET but less than 2.5 in Ge corrected PET; two of 87 regions with pattern B demonstrated an SUV greater than 2.5 in Ge corrected PET and less than 2.5 in CT corrected PET. ConclusionPhysiological bowel motion may result in attenuation differences and subsequent differences in SUVs. Overestimation of fluorodeoxyglucose uptake should not be misinterpreted as disease.

18F-Fluoro-2-deoxyglucose positron emission tomography in the evaluation of gastrointestinal malignancies

Positron emission tomography with 18F-fluoro-2-deoxyglucose is an imaging technology that is demonstrating increasing utility in the evaluation of gastrointestinal malignancies.

PET-CT evaluation of 2-deoxy-2-[18F]fluoro-D-glucose myocardial uptake: effect of respiratory motion.

PURPOSE Using combined positron emission tomography (PET) and computerized tomography (CT) instrumentation, PET measurements of myocardial tracer uptake performed with CT attenuation correction may differ from estimates using 68Germanium transmission correction due to differences in respiratory motion during acquisition. The purpose of this study is to evaluate the effects of respiratory motion on the CT acquisition and emission corrected images, and to evaluate the correlation of diaphragm position with regional differences in myocardial 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake in clinical studies. METHODS A canine myocardial FDG-PET study was performed with controlled ventilation. Attenuation correction was performed with CT scans acquired at end expiration and end inspiration, and throughout multiple respiratory cycles with conventional 68Germanium transmission scan. The mean myocardial FDG activity was evaluated in multiple short axis regions of interest (n=40) using each of these three AC maps. Differences in emission during CT acquisitions were identified and expressed as bias (%) compared to 68Germanium corrected data. Ten patient studies with high myocardial FDG uptake were retrospectively selected from a clinical population referred for whole body oncology studies. All subjects had both CT and 68Germanium AC. After analysis for diaphragm misregistration defined by imaging and diaphragm position, subjects were divided into two groups: Group A controls (n=5) with no or mild misregistration, and Group B (n=5) with moderate or severe diaphragm misregistration. Regional emission bias (n=400 regions) from CT correction was defined by using the 68Germanium attenuation corrected emission as the standard. RESULTS The canine study using end-expiration CT for attenuation correction showed regional overestimation of activity (1.8%+/-0.7% for inferior; 2.0%+/-0.5% for inferolateral) compared to the 68Germanium corrected images. Conversely, the study using end-inspiration CT attenuation correction showed underestimation (-3.9%+/-0.5% for inferior; -4.0%+/-0.6% for inferolateral) of myocardial activity compared to 68Germanium corrected images. In subjects, Group B showed significant relative underestimation of FDG myocardial activity compared to Group A in the regions adjacent to the diaphragm including the inferior (P=0.0003), inferoseptal (P=0.008), and inferolateral (P<0.0001) regions. CONCLUSIONS In canine myocardium, differences in respiration influenced CT attenuation maps and subsequent CT attenuation corrected PET images in the inferolateral and lateral regions. In clinical PET-CT studies, diaphragm misregistration is associated with relative decreased emission activity in inferior, inferoseptal, and inferolateral walls. Nonuniformity of bias in the emission data can affect quantitative accuracy, and therefore, the interpretation of myocardial viability. Further studies are required to determine if the frequency of these findings warrants the use of 68Germanium transmission attenuation correction in myocardial FDG-PET. The quantitative differences between these techniques were typically modest.

MRI detection of myocardial perfusion defects due to coronary artery stenosis with MS‐325

To assess the value of an intravascular, albumin‐targeted contrast agent, MS‐325, in visualizing myocardial ischemia with magnetic resonance imaging (MRI).

Somatostatin receptor scintigraphy and somatostatin therapy in the evaluation and treatment of malignant thymoma.

PURPOSE This report illustrates the potential diagnostic and therapeutic utility of somatostatin receptor scintigraphy and therapy with somatostatin. METHODS In-111 pentetreotide (In-111 octreotide), a somatostatin analog, was used to define the receptor status and the extent of disease in a case of malignant thymoma. RESULTS Subsequent treatment with nonradioactive somatostatin inhibited tumor growth. CONCLUSION In-111 octreotide may be useful to define tumor receptor status and may provide prognostic information useful in determining subsequent therapy.

Castration-Resistant Prostate Cancer Bone Metastasis Response Measured by 18F-Fluoride PET After Treatment with Dasatinib and Correlation with Progression-Free Survival: Results from American College of Radiology Imaging Network 6687

18F-fluoride PET quantitatively images bone metabolism and may serve as a pharmacodynamic assessment for systemic therapy such as dasatinib, a potent SRC kinase inhibitor, with activity in bone. Methods: This was an imaging companion trial (American College of Radiology Imaging Network [ACRIN] 6687) to a multicenter metastatic castration-resistant prostate cancer (CRPC) tissue biomarker–guided therapeutic trial (NCT00918385). Men with bone metastatic CRPC underwent 18F-fluoride PET before and 12 weeks after initiation of dasatinib (100 mg daily). Dynamic imaging was performed over a 15-cm field of view for trial assessments. The primary endpoint was to determine whether changes in 18F-fluoride incorporation in tumor and normal bone occurred in response to dasatinib. Other endpoints included differential effect of dasatinib between 18F-fluoride incorporation in tumor and normal bone, 18F-fluoride transport in bone metastases, correlation with progression-free survival (PFS), prostate-specific antigen, and markers of bone turnover. Results: Eighteen participants enrolled, and 17 underwent interpretable baseline 18F-fluoride PET imaging before initiation of dasatinib. Twelve of 17 patients underwent on-treatment PET imaging. Statistically significant changes in response to dasatinib were identified by the SUVmaxavg (average of maximum standardized uptake value [SUVmax] for up to 5 tumors within the dynamic field of view) in bone metastases (P = 0.0002), with a significant differential 18F-fluoride PET response between tumor and normal bone (P < 0.0001). Changes in 18F-fluoride incorporation in bone metastases had borderline correlation with PFS by SUVmaxavg (hazard ratio, 0.91; 95% confidence interval, 0.82–1.00; P = 0.056). Changes by SUVmaxavg correlated with bone alkaline phosphatase (P = 0.0014) but not prostate-specific antigen (P = 0.47). Conclusion: This trial provides evidence of the ability 18F-fluoride PET to delineate treatment response of dasatinib in CRPC bone metastases with borderline correlation with PFS.