Showing papers by "Kooresh I. Shoghi published in 2012"

Assessment of Progesterone Receptors in Breast Carcinoma by PET with 21-18F-Fluoro-16α,17α-[(R)-(1′-α-furylmethylidene)Dioxy]-19-Norpregn-4-Ene-3,20-Dione

Abstract: This first-in-human study was designed to evaluate the safety and dosimetry of the progesterone analog 21-18F-fluoro-16α,17α-[(R)-(1′-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione (18F-FFNP), as well the feasibility of imaging tumor progesterone receptors (PRs) by PET in breast cancer. Methods: Women with breast cancer underwent PET with 18F-FFNP. Tumor 18F-FFNP uptake was assessed semiquantitatively by determining maximum standardized uptake value and tumor-to-normal breast (T/N) activity ratio and by Logan graphical analysis. The PET results were correlated with estrogen receptor (ER) and PR status, assessed by in vitro assays of the tumor tissue. The biodistribution of 18F-FFNP was measured in patients by whole-body PET, and human dosimetry was estimated. Results: Twenty patients with 22 primary breast cancers (16 PR-positive [PR+] and 6 PR-negative [PR–]) were evaluated. Tumor maximum standardized uptake value was not significantly different in PR+ and PR− cancers (mean ± SD, 2.5 ± 0.9 vs. 2.0 ± 1.3, P = 0.386), but the T/N ratio was significantly greater in the PR+ cancers (2.6 ± 0.9 vs. 1.5 ± 0.3, P = 0.001). In addition, there was a significant correlation between distribution volume ratio and T/N ratio (r = 0.89; P = 0.001) but not between distribution volume ratio and either PR status or standardized uptake value, likely because of small sample size. On the basis of whole-body PET data in 12 patients, the gallbladder appeared to be the dose-limiting organ, with an average radiation dose of 0.113 mGy/MBq. The whole-body dose was 0.015 mGy/MBq, and the effective dose was 0.020 mSv/MBq. No adverse effects of 18F-FFNP were encountered. Conclusion:18F-FFNP PET is a safe, noninvasive means for evaluating tumor PRs in vivo in patients with breast cancer. The relatively small absorbed doses to normal organs allow for the safe injection of up to 440 MBq of 18F-FFNP.

Quantitative accuracy of MAP reconstruction for dynamic PET imaging in small animals

Abstract: Purpose: Iterative reconstruction algorithms are becoming more commonly employed in positron emission tomography (PET) imaging; however, the quantitative accuracy of the reconstructed images still requires validation for various levels of contrast and counting statistics. Methods: The authors present an evaluation of the quantitative accuracy of the 3D maximuma posteriori (3D-MAP) image reconstruction algorithm for dynamic PET imaging with comparisons to two of the most widely used reconstruction algorithms: the 2D filtered-backprojection (2D-FBP) and 2D-ordered subsets expectation maximization (2D-OSEM) on the Siemens microPET scanners. The study was performed for various levels of count density encountered in typical dynamic scanning as well as the imaging of cardiac activity concentration in small animal studies on the Focus 120. Specially designed phantoms were used for evaluation of the spatial resolution, image quality, and quantitative accuracy. A normal mouse was employed to evaluate the accuracy of the blood time activity concentration extracted from left ventricle regions of interest (ROIs) within the images as compared to the actual blood activity concentration measured from arterial blood sampling. Results: For MAP reconstructions, the spatial resolution and contrast have been found to reach a stable value after 20 iterations independent of the β values (i.e., hyper parameter which controls the weight of the penalty term) and count density within the frame. The spatial resolution obtained with 3D-MAP reaches values of ∼1.0 mm with a β of 0.01 while the 2D-FBP has value of 1.8 mm and 2D-OSEM has a value of 1.6 mm. It has been observed that the lower the hyper parameter β used in MAP, more iterations are needed to reach the stable noise level (i.e., image roughness). The spatial resolution is improved by using a lower β value at the expense of higher image noise. However, with similar noise level the spatial resolution achieved by 3D-MAP was observed to be better than that by 2D-FBP or 2D-OSEM. Using an image quality phantom containing hot spheres, the estimated activity concentration in the largest sphere has the expected concentration relative to the background area for all the MAP images. The obtained recovery coefficients have been also shown to be almost independent of the count density. 2D-FBP and 2D-OSEM do not perform as well, yielding recovery coefficients lower than those observed with 3D-MAP (approximately 33% lower for the smallest sphere). However, a small positive bias was observed in MAP reconstructed images for frames of very low count density. This bias is present in the uniform area for count density of less than 0.05 × 106 counts/ml. For the dynamic mouse study, it was observed that 3D-MAP (even gated at diastole) cannot predict accurately the blood activity concentration due to residual spill-over activity from the myocardium into the left ventricle (approximately 15%). However, 3D-MAP predicts blood activity concentration closer to blood sampling than 2D-FBP. Conclusions: The authors observed that 3D-MAP produces more accurate activity concentration estimates than 2D-FBP or 2D-OSEM at all practical levels of statistics and contrasts due to improved spatial resolution leading to lesser partial volume effect.

Feasibility and Dosimetry Studies for 18F-NOS as a Potential PET Radiopharmaceutical for Inducible Nitric Oxide Synthase in Humans

Abstract: Nitric oxide (NO), the end product of the inducible form of NO synthase (iNOS), is an important mediator of a variety of inflammatory diseases. Therefore, a radiolabeled iNOS radiopharmaceutical for assessing iNOS protein concentration as a marker for its activity would be of value to the study and treatment of NO-related diseases. We recently synthesized an 18F-radiolabeled analog of the reversible NOS inhibitor, 2-amino-4-methylpyridine (18F-NOS), and confirmed its utility in a murine model of lung inflammation. To determine its potential for use in humans, we measured 18F-NOS myocardial activity in patients after orthotopic heart transplantation (OHT) and correlated it with pathologic allograft rejection, tissue iNOS levels, and calculated human radiation dosimetry. Methods: Two groups were studied—a kinetic analysis group and a dosimetry group. In the kinetic analysis group, 10 OHT patients underwent dynamic myocardial 18F-NOS PET/CT, followed by endomyocardial biopsy. Myocardial 18F-NOS PET was assessed using volume of distribution; standardized uptake values at 10 min; area under the myocardial moment curve (AUMC); and mean resident time at 5, 10, and 30 min after tracer injection. Tissue iNOS levels were measured by immunohistochemistry. In the dosimetry group, the biodistribution and radiation dosimetry were calculated using whole-body PET/CT in 4 healthy volunteers and 12 OHT patients. The combined time–activity curves were used for residence time calculation, and organ doses were calculated with OLINDA. Results: Both AUMC at 10 min (P

Quantification of Skeletal Blood Flow and Fluoride Metabolism in Rats using PET in a Pre-Clinical Stress Fracture Model

Abstract: Purpose Blood flow is an important factor in bone production and repair, but its role in osteogenesis induced by mechanical loading is unknown. Here, we present techniques for evaluating blood flow and fluoride metabolism in a pre-clinical stress fracture model of osteogenesis in rats.

Artificial tissue bioreactor (ATB) for biological and imaging applications

Abstract: Three-dimensional (3D) culture systems are increasingly applied to study tissue biology. In this work, we report on the development of an artificial tissue bioreactor (ATB) designed to simulate the 3D structure and microenvironment of tissues in vivo, with multiple avenues of sampling, including the tissue chamber, for downstream analysis. Additionally, the ATB is integrated with the microPET Focus F220 for in-vivo imaging applications. As a proof-of-concept, we characterized the effects of lipids on glucose utilization using HepG2 cells. ATB studies were performed pre- and post- therapeutic intervention with the PPAR-γ agonist pioglitazone. In parallel, Glucose Tolerance Test (GTT) is performed on media samples to assess glucose uptake by cells as a measures of insulin signaling sensitivity. Fatty acid uptake in the ATB cell chamber is measured using [11C]Palmitate with microPET imaging. Overall, the ATB will facilitate the use of existing and novel radiopharmaceuticals in discovery of validating and translating insights derived from ATB studies to pre-clinical animal studies, to clinical evaluation.