Annarita Savi

Biodistribution of Tc-99m methoxy-isobutyl-isonitrile (MIBI) in humans

Hexakis (methoxyisobutilisonitrile) technetium(I), 99mTc-MIBI, has been proposed for myocardial perfusion studies. We have evaluated the biodistribution of this new agent in normal volunteers at rest and after stress. The biodistribution of 99mTc-MIBI is characterized by rapid blood clearance and a consequently early myocardial uptake. The initial intense hepatic activity is cleared into the gallbladder at 1 h after injection, and the best target to non target ratio is observed at 60–90 min after injection. Absorbed radiation dose calculations show that the thyroid is the critical target organ (230 mRad/mCi at rest), presumably because of 99mTc-pertechnetate generated in vivo. Our results indicate that 99mTc-MIBI is a promising tracer for myocardial perfusion imaging.

Scatter correction techniques in 3D PET: a Monte Carlo evaluation

In this work a Monte Carlo software package, PET-EGS, designed to simulate realistic PET clinical studies, was used to assess three different approaches to scatter correction in 3D PET: analytical (gaussian fitting technique), experimental (dual energy window technique), probabilistic (Monte Carlo technique). Phantom and clinical studies were performed by 3D PET and simulated by PET-EGS. Clinical studies were simulated assuming PET emission/transmission multivolume images as voxelized source objects describing the distribution of both the radioactivity and attenuation coefficients and accounting for out-of-field activity and media. The accuracy of PET-EGS in modeling the physical response of a 3D PET scanner was assessed by statistical comparison between measured and total (scatter+unscatter) simulated distributions (probability for the two distributions to be the same distribution: p>0.95). The accuracy of the scatter models, for each scatter correction technique, was evaluated on sinograms by statistical comparison between the estimated and the simulated scatter distributions (agreement <1 /spl sigma/). The accuracy of scatter correction was evaluated on sinograms by comparison between scatter corrected and simulated unscatter distributions (residual scatter fraction <13 %).

Correlation of SPECT and PET cardiac images by a surface matching registration technique

Complementary information provided by Single Photon and Positron Emission Tomography (SPECT and PET) in nuclear cardiology allows a better comprehension of the physiopathology of the heart. In this work a surface matching registration technique is evaluated in the spatial correlation of SPECT and PET cardiac images. The method is based on matching correspondent anatomical surfaces extracted from transmission (TR) SPECT and PET studies, usually performed for attenuation correction. The accuracy of the technique was evaluated by phantom experiments and on patient data (201Tl SPECT and 13NH3 PET perfusion studies). An application of the method is presented for the correlation of SPECT 201Tl perfusion and PET 18FDG metabolic studies in the evaluation of myocardial viability.

Spatial registration of echocardiographic and positron emission tomographic heart studies

A method has been developed to match corresponding heart regions from functional echocardiographic (Echo) and metabolic fluorine-l8-fluoro-2-deoxy-d-glucose ([18F]FDG) positron emission tomography (PET) studies in individual patients. Echo and PET images are spatially correlated by determining homologous anatomical landmarks (the two papillary muscles and the inferior junction of the right ventricle), identifiable in images obtained by both acquisition modalities. Echo-PET image registration is first performed in the plane identified by the three landmarks, using a rigid rotate-translate scale model. The registration parameters are then used to transform the whole PET volume. This allows a consistent Echo-PET regional analysis, according to a segmental subdivision of the heart. The technique was tested on patients. The overlay of Echo and PET registered images proved the reliability of realignment of the three markers and a good spatial correlation of myocardial walls. This approach to image registration could be applied to other acquisition modalities (such as magnetic resonance imaging and single-photon emission tomography), provided that the three anatomical landmarks are visualized.

Assessment of myocardial perfusion and viability with technetium-99m methoxyisobutylisonitrile and thallium-201 rest redistribution in chronic coronary artery disease

We compare thallium-201 rest redistribution and fluorine-18 fluorodeoxyglucose ([18F]FDG) for the assessment of myocardial viability within technetium-99m methoxyisobutylisonitrile (MIBI) perfusion defects in 27 patients with chronic stable coronary artery disease. The following studies were performed: (1) stress99mTc-MIBI, (2) rest99mTc-MIBI, (3)201T1 rest-redistribution single-photon emission tomography, (4) [18F]FDG positron emission tomography. The left ventricle was devided into 11 segments on matched tomographic images. The segment with the highest activity at stress was taken as the reference (activity=100%). Perfusion defects at99mTc-MIBI rest were classified as severe (activity<50%), moderate (activity 50%–60%) or mild (activity 60%–85%). Uptakes of [18F]FDG and rest-redistributed201Tl were recognized as significant if they exceeded 50% of that in the reference segment. Among the 33 segments with severe99mTc-MIBI rest perfusion defects, 21 had significant [18F]FDG and 10 significant rest-redistributed201Tl uptake. As regards the 37 segments with moderate defects, [18F]FDG was present in 29 and201Tl in 31, while of the 134 segments with mild defects, 128 showed [18F]FDG uptake, and 131,201Tl uptake. In conclusion, there is an inverse relationship between the severity of99mTc-MIBI perfusion defects and the uptake of rest-redistributed201Tl and [18F]FDG. Both tracers are adequate markers of viability in mild and moderate defects; in severe defects201Tl might underestimate the presence of viability as assessed by [18F]FDG.

Lesion detectability and quantification in PET/CT oncological studies by Monte Carlo simulations

The aim of this work was to assess lesion detectability and quantification in whole body oncological /sup 18/F-FDG studies performed by a state-of-the-art integrated Positron Emission Tomograph/computed tomography (PET/CT) system. Lesion detectability and quantification were assessed by a Monte Carlo (MC) simulation approach as a function of different physical factors (e.g., attenuation and scatter), image counting statistics, lesion size and position, lesion-to-background radioactivity concentration ratio (L/B), and reconstruction algorithms. The results of this work brought to a number of conclusions. The MC code PET-electron gamma shower (EGS) was accurate in simulating the physical response of the considered PET/CT scanner (>90%). PET-EGS and patient-derived phantoms can be used in simulating/sup 18/ F-FDG PET oncological studies. Counting statistics is a dominant factor in lesion detectability. Correction for scatter (from both inside and outside the field of view) is needed to improve lesion detectability. Iterative reconstruction and attenuation correction must be used to interpret clinical images. Re-binning algorithms are appropriate for whole-body oncological data. A MC-based method for correction of partial volume effect is feasible. For the considered PET/CT system, limits in lesion detectability were determined in situations comparable to those of real oncological studies: at a L/B=3 for lesions of 12 mm diameter and at a L/B=4 for lesions of 8 mm diameter.

Frequency weighted least squares reconstruction of truncated transmission SPECT data

A least squares technique for reconstructing truncated data is presented. The method involves including the ramp filter into the system matrix. The sinogram is extrapolated with zeros for filtering but extrapolated values are not considered during backward and forward projections. The new matrix leads to a frequency weighted least squares criterion. Tikhonov regularization and a priori information are considered. For the O-order regularization, the resulting images are biased but it is shown that this bias is recovered by a simple scaling process. First and second order regularizations provide true restoration. The technique is applied to simulated and real transmission SPECT data. Results show that the frequency least squares criterion is a valuable approach for efficiently reconstructing truncated sinograms.

In Vivo Demonstration of Insulin-Receptor Defect With 123I-Labeled Insulin and Scintigraphic Scanning in Severe Insulin Resistance

Objective Insulin-receptor function in humans is usually studied in vitro on readily available cells, e.g., erythrocytes and fibroblasts. Although these cells are not metabolically important targets for insulin action, information derived from them are often taken as representative of other tissues. The aim of this study was to investigate insulin receptors in vitro on erythrocytes and in vivo on one of the main insulin-target organs, the liver. Research Design and Methods A 16-yr-old girl affected by severe insulin resistance was identified. Insulin receptor binding was measured on the erythrocytes of the patient and of 6 nondiabetic volunteers. The biodistribution of 123I-labeled insulin was studied in vivo by scintigraphic scanning in the insulin-resistant patient and in 10 nondiabetic volunteers. Results Erythrocytes of this patient displayed a markedly reduced [125I]insulin binding. In vivo 123I-insulin biodistribution was characterized by lack of hormone uptake by the liver (4 vs. 21% of the injected dose in control subjects) contrasting with intense accumulation of radioactivity in the kidneys. Conclusions Our studies show that defects of insulin binding can be directly demonstrated in vivo on liver receptors with a noninvasive technique with low radiotoxicity.

First evaluation of PET based human biodistribution and dosimetry of 18F-FAZA, a tracer for imaging tumor hypoxia

18F-labeled fluoroazomycinarabinoside (18F-FAZA) is a PET biomarker for noninvasive identification of regional tumor hypoxia. The aim of the present phase I study was to evaluate the biodistribution and dosimetry of 18F-FAZA in non–small cell lung cancer patients. Methods: Five patients awaiting surgical resection of histologically proven or radiologically suspected non–small cell lung cancer were prospectively enrolled in the study. The patients underwent PET/CT after injection of 371 ± 32 MBq of 18F-FAZA. The protocol consisted of a 10-min dynamic acquisition of the heart to calculate the activity in blood, followed by 4 whole-body PET/CT scans, from the vertex to the mid thigh, at 10, 60, 120, and 240 min after injection. Urine samples were collected after each imaging session and at 360 min after injection. Volumes of interest were drawn around visually identifiable source organs to generate time–activity curves. Residence times were determined from time–activity curves, and effective doses to individual organs and the whole body were calculated using OLINDA/EXM 1.2 for the standard male and female phantoms. Results: Blood clearance was characterized by a rapid distribution followed by first-order elimination. The highest uptake was in muscle and liver, with respective percentage injected activity (%IA) peaks of 42.7 ± 5.3 %IA and 5.5 ± 0.6 %IA. The total urinary excretion was 15 %IA. The critical organ, with the highest absorbed radiation doses, was the urinary bladder wall, at 0.047 ± 0.008 and 0.067 ± 0.007 mGy/MBq for the 2- and 4-h voiding intervals, respectively. The effective doses for the standard male and female phantoms were 0.013 ± 0.004 and 0.014 ± 0.004 mSv/MBq, respectively, depending on the voiding schedule. Conclusion: With respect to the available literature, the biodistribution of 18F-FAZA in humans appeared to be slightly different from that in mice, with a low clearance in humans. Therefore, use of animal data may moderately underestimate radiation doses to organs in humans. Our dosimetry data showed that a 370-MBq injection of 18F-FAZA is safe for clinical use, similar to other widely used PET ligands. In particular, the effective dose is not appreciably different from those obtained with other hypoxia tracers, such as 18F-fluoromisonidazole.

99mTc-2GAM: a tracer for renal imaging.

We propose a renal imaging agent, the 99mTc complex of the bidentate-N,S chelate N-(mercaptoacetyl)glycine (99mTc-2GAM), with the imaging characteristics of 99mTc-DMSA but a faster kidney uptake; chemical evidence supports the formulation of 99mTc-2GAM as [Tc(v)(O)(GAM)2]-. After biodistribution and toxicity studies in animals, 99mTc-2GAM was evaluated in five normal volunteers. 99mTc-2GAM is rapidly cleared from the blood (t1/2 = 9 min) and 50% of the ID is excreted in the urine in the first 2 h. Dynamic data show a rapid renal uptake that increases up to 1 h with no significant wash-out between 1 and 8 h. The uptake in each kidney ranges from 11.3% to 20.7% ID. Low, stable liver uptake is observed. No significant activity is detected in other organs. We showed no differences between 99mTc-2GAM and 99mTc-DMSA compared in three patients with unilateral kidney disease. We conclude that 99mTc-2GAM has good practical and dosimetric features for renal imaging.