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Bennett B Chin,
Anita Hjelemand,
Jeremy Rich,
Haijing Song,
Christopher Lascola,
Robert Storms,
Roger McLendon,
Robert Reiman,
Kim L Greer,
Scott D Metzler,
Darryl McDougald,
Diana Dai,
Ganesan Vaidyanathan
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ABSTRACT: Chloroquine has demonstrated high affinity for aldehyde dehydrogenase 1A1 (ALDH1), an enzyme expressed in the highly tumorigenic CD133+ brain tumor initiating subpopulation. The purpose of this study is to report the novel synthesis of a chloroquine analogue, n.c.a. iodoquine, and the in vitro and in vivo uptake in cells with high ALDH1 content.
Iodoquine was synthesized in novel no-carrier-added forms (n.c.a.) for both 125I and 123I. I25I IQ and 18F FDG cell uptake assays were performed in the L1210 and L1210cpa (cyclophosphamide resistant), A549, and MG456 glioblastoma cell lines. Uptake was expressed as a percent of the administered activity. 125I IQ biodistribution studies assessed organ uptake at 1, 4, and 24 hours after IV administration (n= 15 total; 5 mice/timepoint). Radiation dosimetry estimates were calculated using standard OLINDA/EXM software. In vivo imaging of 123I IQ uptake in MG456 glioblastoma mouse model (n=10) was performed with small animal high resolution micro-SPECT. Autoradiography and histology co-localized radiotracer and tumor biodistribution. Uptake in MG456 glioblastoma tumors was quantified with gamma counting.
L1210 cpa (high ALDH1) showed significantly higher 125I IQ uptake compared to the parental L1210 (low ALDH1) for all time points through 4 hours (20.7% ± 1.4% versus 11.0% ± 0.5%; 21.3% ± 0.9% versus 11.0% ± 0.4%; 20.6% ± 0.7% versus 9.4% ± 0.3%; and 15.7% ± 0.7% versus 7.5% + 0.4% at 30 minutes, and 1, 2 and 4 hours, respectively; p < 0.001 for all time points). In the CD133+ fraction of MG456 glioblastoma cell line, IQ uptake was significantly higher compared to FDG at all time points through 4 hours (81.5% ± 0.9% versus 1.3% ± 0.1%; 88.8% ± 0.4% versus 1.3% ± 0.1%; 87.8% ± 2.1% versus 1.7% ± 0.2%; and 87.0% ± 2.4% versus 1.8% ± 0.1 at 30 minutes, and 1, 2 and 4 hours, respectively; p > 0.001 for all time points). The A549 lung cancer cell line also showed high IQ uptake through 4 hours. IQ normal biodistribution studies showed rapid renal excretion and very low normal background brain activity after IV administration. In vivo micro-SPECT images showed mild uptake in larger MG456 glioblastomas (n=6) as verified with autoradiography and histology. Gamma well counter uptake in large tumors was 2.3% ± 0.48% ID/g (n=5).
Iodoquine localizes to cells with high ALDH1 content. Cell assays show high 125I IQ uptake in the MG456 cell line, and in vivo micro-SPECT imaging showed mild 123I IQ uptake in MG456 glioblastomas. Further studies are necessary to investigate 131I IQ as a potential therapeutic agent targeting the highly tumorigenic CD133+ brain tumor stem cell subpopulation.
Current radiopharmaceuticals. 08/2011; 5(1):47-58.
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ABSTRACT: To advance the science and clinical application of stem cell therapy, the availability of a highly sensitive, quantitative and translational method for tracking stem cells would be invaluable. Because hematopoetic stem cells express high levels of the cytosolic enzyme aldehyde dehydrogenase-1A1 (ALDH1), we sought to develop an agent that is specific to ALDH1 and thus to cells expressing the enzyme. Such an agent might be also helpful in identifying tumors that are resistant to cyclophosphomide chemotherapy because ALDH1 is known to be responsible for this resistance.
We developed schemes for the synthesis of two radioiodinated aldehdyes - N-formylmethyl-5-[*I]iodopyridine-3-carboxamide ([*I]FMIC) and 4-diethylamino-3-[*I]iodobenzaldehyde ([*I]DEIBA)-at no-carrier-added levels from their respective tin precursors. These agents were evaluated using pure ALDH1 and tumor cells that expressed the enzyme.
The average radiochemical yields for the synthesis of [(125)I]FMIC and [(125)I]DEIBA were 70+/-5% and 47+/-14%, respectively. ALDH1 converted both compounds to respective acids suggesting their suitability as ALDH1 imaging agents. Although ability of ALDH1 within the cells to oxidize one of these substrates was shown, specific uptake in ALDH-expressing tumor cells could not be demonstrated.
To pursue this approach for ALDH1 imaging, radiolabeled aldehydes need to be designed such that, in addition to being good substrates for ALDH1, the cognate products should be sufficiently polar so as to be retained within the cells.
Nuclear Medicine and Biology 11/2009; 36(8):919-29. · 3.02 Impact Factor
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Bennett B Chin,
Scott D Metzler,
Anthony Lemaire,
Antonio Curcio,
Sreekanth Vemulapalli,
Kim L Greer,
Neil A Petry,
Timothy G Turkington,
R Edward Coleman,
Howard Rockman,
Ronald J Jaszczak
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ABSTRACT: To prospectively determine feasibility of evaluating murine left ventricular (LV) function with electrocardiographically (ECG)-gated blood pool single photon emission computed tomography (SPECT).
All animal studies had institutional animal care and use committee approval. SPECT was performed with conventional time-binned acquisition (eight frames per ECG cycle) in normal mice (normal group A, n = 6) and mice with myocardial infarction (MI) (n = 8). To determine feasibility of high temporal resolution and rapid data acquisition, another group of normal mice (normal group B, n = 4) underwent imaging with conventional (eight-frame) time-binned and list-mode (LM) acquisitions. LM acquisitions were reconstructed with eight and 16 frames per ECG cycle and 10 minutes of data (short LM). SPECT images were assessed visually, and LV-to-lung background activity ratios were calculated. LV end-systolic and end-diastolic volumes were defined with a phase analysis and threshold method. LV ejection fraction (LVEF) was calculated from LV volumes and count-based methods (n = 18 mice). Fractional shortening (FS) at echocardiography defined MI dysfunction (mild MI: FS > or = 50%; severe MI: FS < 50%). Group means were compared for significant differences with analysis of variance.
ECG-gated blood pool SPECT demonstrated normal, concentric LV contraction in all normal mice (n = 10). LV-to-lung background ratio was more than 10:1 (range, 10.3-29.4; n = 18). Focal wall motion abnormalities were detected at SPECT both visually and with phase analysis in all mice with severe MI (n = 5). Mice with severe MI had significantly lower LVEF than normal group A mice (32% +/- 14 [standard deviation] vs 64% +/- 8%; P < .001). All mice with mild MI (n = 3) had normal contraction and LVEF. In paired acquisitions in normal group B mice, all reconstructions (n = 16) showed normal LV contraction. LVEF was not significantly different (P = .88) between time-binned (71% +/- 12), eight-frame LM (71% +/- 12), 16-frame LM (77% +/- 10), and short LM (73% +/- 14) reconstructions.
Murine LV functional assessment is feasible with high spatial and temporal resolution ECG-gated blood pool SPECT. LV dysfunction can be quantified and focal wall motion abnormalities detected in the MI model of heart failure.
Radiology 12/2007; 245(2):440-8. · 5.73 Impact Factor
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Sreekanth Vemulapalli,
Scott D Metzler,
Gamal Akabani,
Neil A Petry,
Nelsen J Niehaus,
Xialin Liu,
Nikhil H Patil,
Kim L Greer,
Ronald J Jaszczak,
R Edward Coleman,
Chunming Dong,
Pascal J Goldschmidt-Clermont, Bennett B Chin
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ABSTRACT: To determine the feasibility of in vivo localization and quantification of indium 111 (111In)-oxine-labeled bone marrow (BM) with high-resolution whole-body helical single photon emission computed tomography (SPECT) in an established murine model of atherosclerosis and vascular repair.
The institutional animal care and use committee approved this study. BM from young B6 Rosa 26 Lac Z+/+ mice was radiolabeled with 111In-oxine. On days 1, 4, and 7 after administration of radiolabeled cells, five C57/BL6 apolipoprotein E-deficient mice and five wild-type (WT) control mice were imaged with whole-body high-resolution helical SPECT. Quantification with SPECT was compared with ex vivo analysis by means of gamma counting. Autoradiography and beta-galactosidase staining were used to verify donor cell biodistribution. Linear regression was used to assess the correlation between continuous variables. Two-tailed Student t test was used to compare values between groups, and paired two-tailed t test was used to assess changes within subjects at different time points.
SPECT image contrast was high, with clear visualization of BM, liver, and spleen 7 days after administration of radiolabeled cells. SPECT revealed that 42% and 58% more activity was localized to the aorta and BM (P<.05 for both), respectively, in apolipoprotein E-deficient mice versus WT mice. Furthermore, 28% and 27% less activity was localized to the liver and spleen (P<.05 for both), respectively, in apolipoprotein E-deficient mice versus WT mice. SPECT and organ gamma counts showed good quantitative correlation (r=0.9). beta-Galactosidase staining and microautoradiography of recipient aortas showed donor cell localization to the intima of visible atherosclerotic plaque but not to unaffected regions of the vessel wall.
High-resolution in vivo helical pinhole SPECT can be used to monitor and quantify early biodistribution of 111In-oxine-labeled BM in a murine model of progenitor cell therapy for atherosclerosis.
Radiology 02/2007; 242(1):198-207. · 5.73 Impact Factor
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ABSTRACT: (18)F-fluoro-2-deoxyglucose positron emission tomography has demonstrated high accuracy in the staging and evaluation of colorectal and esophageal carcinomas. FDG PET is demonstrating increasing utility in a number of other gastrointestinal tumours and clinical scenarios. The established clinical indications for its use, the diagnostic accuracy, and limitations will be reviewed. Data on the emerging indications and limitations for pancreatic, hepatocellular, and gastric carcinomas, as well as gastrointestinal stromal tumours, cholangiocarcinoma, and carcinoma of unknown primary will also be briefly discussed. The use of combined PET-CT is demonstrating further improvements in diagnostic accuracy.
Baillière' s Best Practice and Research in Clinical Gastroenterology 03/2006; 20(1):3-21. · 2.46 Impact Factor
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12/2005: pages 89-103;
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IEEE Trans. Med. Imaging. 01/2005; 24:853-862.
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ABSTRACT: In 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.
Twelve 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.
One 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.
Physiological bowel motion may result in attenuation differences and subsequent differences in SUVs. Overestimation of fluorodeoxyglucose uptake should not be misinterpreted as disease.
Nuclear Medicine Communications 04/2004; 25(3):221-5. · 1.40 Impact Factor
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ABSTRACT: TSH stimulates thyrocyte metabolism, glucose transport, and glycolysis. 2-Deoxy-2-[18F]fluoro-D-glucose (FDG) is a glucose analog used in positron emission tomography (PET) to detect occult well-differentiated thyroid carcinoma. The objective of this study was to examine the effects of recombinant human TSH (rTSH) on FDG PET uptake in patients with residual or recurrent disease. Seven patients with well-differentiated thyroid carcinoma, negative 131-I scintigraphy, and biochemical evidence of residual disease were randomized and prospectively studied with FDG PET both on thyroid hormone suppression and rTSH stimulation within 1 wk. All lesions seen on the TSH suppression scans were seen on the rTSH stimulation studies. rTSH stimulation studies identified four additional lesions not seen on TSH suppression. One patient was positive on rTSH stimulation alone. The mean (2.54 +/- 0.72 vs. 1.79 +/- 0.88) and maximum (2.49 +/- 0.95 vs. 1.74 +/- 0.81) lesion to background ratios were significantly higher with rTSH stimulation, compared with TSH suppression (P = 0.02 for both). rTSH stimulation improves the detectability of occult thyroid metastases with FDG PET, compared with scans performed on TSH suppression.
Journal of Clinical Endocrinology & Metabolism 02/2004; 89(1):91-5. · 6.50 Impact Factor
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Thyroid 01/2004; 13(12):1183-4. · 4.79 Impact Factor
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ABSTRACT: To investigate the effects of intravenous contrast agents on quantitative values obtained with a combined positron emission tomographic (PET) and computed tomographic (CT) scanner by using several phantoms and a dog.
Fluorine 18 fluorodeoxyglucose (FDG) was mixed with different concentrations of contrast agent with the same syringe (phantom 1), and the phantom was scanned. After image reconstruction with various attenuation maps, radioactivity concentrations were compared. Then, FDG solutions with (phantom 2) or surrounded by (phantom 3) various concentrations of contrast agent were scanned repeatedly, and radioactivity concentration was compared. Finally, PET and CT with and without contrast agent were performed in a dog. PET images were reconstructed by using different attenuation maps, and radioactivity concentrations were compared. The radioactivity concentration on germanium 68 (68Ge)-based corrected images was regarded as standard, and percentage bias, defined as difference divided by measured activity of 68Ge-based corrected images, was assessed. The relationship between the concentration of contrast agent and the percentage bias was assessed with the Pearson coefficient r, and the significance of correlations was evaluated with the Fisher z test.
All phantom studies demonstrated that presence of a contrast agent resulted in overestimation of emission data. CT numbers showed a strong positive correlation with the percentage bias in phantoms 2 (r = 0.999) and 3 (r = 0.987); the maximum percentage bias at 1,360 HU reached approximately 45%. These effects were independent of FDG concentration. In a canine model, presence of a contrast agent also increased emission activity, but the percentage bias was less than 15% in the liver and smaller in all other organs except the kidney (26%).
High concentrations of a contrast agent caused considerable overestimation of apparent tracer activity in phantom studies; however, the emission bias was relatively modest in vivo, except in areas with very high contrast agent concentrations.
Radiology 07/2003; 227(3):817-24. · 5.73 Impact Factor
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ABSTRACT: Fallopian tube carcinoma is a rare malignancy that commonly recurs after initial surgical resection. New combined instrumentation with co-registered PET and CT is a new technique that combines functional and anatomic imaging to detect metastatic disease that may be difficult to detect with either modality alone.
We present two cases of suspected fallopian tube carcinoma recurrence demonstrating the unique potential of combined PET-CT using 18F-fluoro-2-deoxyglucose (FDG). These cases demonstrate the unique capability to detect and localize metastatic disease when serum CA-125, laparoscopy, and CT scan alone were unable to detect recurrence.
PET-CT with FDG may prove to be a sensitive and accurate method for detection of metastatic disease and may influence the clinical management of recurrent fallopian tube carcinoma.
Gynecologic Oncology 01/2003; 87(3):323-6. · 3.89 Impact Factor
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ABSTRACT: To evaluate the ability of Gadomer-17 to depict perfusion defects in a closed-chest swine model of single-vessel coronary artery disease.
Twelve pigs underwent closed-chest placement of a flow reducer for 70%-90% luminal stenosis in the proximal left anterior coronary artery. Magnetic resonance (MR) perfusion imaging with Gadomer-17 and gadopentetate dimeglumine, microsphere blood flow (MBF) testing, and technetium 99m ((99m)Tc) 2 methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) were performed during dipyridamole vasodilation. Comparisons of percentage signal intensity (SI) increase (PSIC) in remote and ischemic myocardium were made with repeated measurements analysis of variance after injection of both tracers.
Perfusion defects and reduced PSIC in the anterior ischemic versus the inferior remote myocardium could be identified after injection of both Gadomer-17 (PSIC, 66% +/- 30 [mean +/- SD] vs 100% +/- 32, respectively; P <.001) and gadopentetate dimeglumine (PSIC, 49% +/- 31 vs 81% +/- 43, respectively; P <.005). The size of perfusion defect depicted with both tracers was highly correlated with defect size at (99m)Tc MIBI SPECT (r = 0.69, P <.05 for Gadomer-17 and r = 0.60, P =.05 for gadopentetate dimeglumine) and with areas of reduced MBF (r = 0.70, P <.05 for Gadomer-17 and r = 0.80, P <.05 for gadopentetate dimeglumine). PSIC also correlated with MBF (r = 0.89, P <.001 for Gadomer-17 and r = 0.75, P <.001 for gadopentetate dimeglumine). Gadomer-17 allowed differentiation of ischemic from nonischemic myocardium, as demonstrated by reduced PSIC (PSIC, 48% +/- 38 vs 72% +/- 31, respectively; P <.001) until 20 minutes after contrast material injection. In contrast, differentiation of ischemic from nonischemic myocardium was possible only until 55 seconds after injection of gadopentetate dimeglumine (PSIC, 36% +/- 24 vs 56% +/- 27, respectively; P <.005) but not at any time point thereafter.
With the study conditions, Gadomer-17 provided more prolonged differentiation of ischemic from remote myocardium than that with gadopentetate dimeglumine.
Radiology 11/2002; 225(1):104-12. · 5.73 Impact Factor
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ABSTRACT: Iterative reconstruction (IR) is a statistical reconstruction method that may be influenced by high background activity such as in the liver. Recently developed combined positron emission tomography (PET) and computerized tomography (CT) instrumentation utilizes CT attenuation correction that may also differ compared to 68Germanium (68Ge) segmented attenuation correction (IR SAC). Quantitative differences could affect the clinical interpretation of metastatic foci and subsequent response to therapy. The purpose of this study is to characterize potential quantitative differences specifically in hepatic metastases.
Thirty-three metastatic liver lesions in 23 patients were evaluated. Whole-body 2-deoxy-2[18F]fluoro-D-glucose(FDG) PET images were obtained on a dedicated PET-CT device and reconstructed with IR and CT measured attenuation correction (IR CT MAC), IR and 68Ge segmented attenuation correction, and also with filtered back-projection and segmented attenuation correction (FBP SAC). Regions of interest over the liver lesions (L) and liver background (B) were drawn on FBP SAC images and superimposed on the co-registered IR CT MAC and IR SAC images for comparison. To identify the individual effects of IR and CT attenuation correction, IR SAC was first compared to FBP SAC, followed by a comparison of IR CT MAC and IR SAC. Differences were expressed as bias (%) and compared to FBP SAC.
Compared to FBP SAC, IR SAC showed significantly lower liver lesion (mean bias -7.1%; P < 0.00001), significantly higher liver background (mean bias -3.5%; P = 0.005), and significantly lower L/B ratio (mean bias -10.1%; P < 0.00001). Compared to IR SAC, the IR CT MAC showed small but not statistically significant increases in liver lesion (mean bias 3.0%; P = 0.1) and liver background (mean bias 4.3%; P = 0.09), and no significant difference in L/B ratio (mean bias -1.3%; P = 0.5). The overall effect of IR CT MAC compared to FBP SAC was a significant decrease in liver lesion (mean bias -4.2%; P = 0.002), significant increase in liver background (mean bias 8.7%; P = 0.002), and significantly lower L/B (mean bias -11.1%; P < 0.00001) compared to FBP SAC.
Compared to FBP, IR resulted in significantly lower mean hepatic tumor activity, higher mean liver background activity, and lower L/B activity, but these differences were modest. These differences were similarly seen in the CT corrected IR CT MAC when compared to FBP SAC. CT attenuation correction did not result in significant differences when compared to 68Ge correction. Although the differences in IR CT MAC were modest, consistent reconstruction methods are important to decrease the measurement variability and improve reproducibility.
Molecular Imaging & Biology 11/2002; 4(6):399-409. · 3.84 Impact Factor
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ABSTRACT: To evaluate the clinical significance of differences in 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) lymph node standardized uptake values (SUV) in human immunodeficiency virus (HIV) infection using iterative reconstruction with segmented attenuation correction (IR SAC) compared to filtered back-projection with measured attenuation correction (FBP MAC).
Seven patients with HIV infection and multiple focal lymph node abnormalities were investigated with whole-body FDG-PET. Mean and maximum SUVs from lymph node regions of interest (n = 961) were compared for quantitative differences between reconstruction techniques.
IR MAC resulted in significantly lower mean SUV [0.06; 95% (confidence interval (CI)) = 0.04-0.07] and maximum SUV (0.82; 95% CI = 0.77-0.88) values compared to FBP MAC. With IR, segmentation of attenuation correction (AC) resulted in significantly higher mean SUV (0.12; 95% CI = 0.11-0.13) and maximum SUV (0.21; 95% CI = 0.18-0.23) values compared to IR MAC. The overall effect of both IR and SAC was a slight but significant increase in mean SUV (0.06; 95% CI = 0.06-0.08; bias = 2.1%) and a significant decrease in maximum SUV (0.62; 95% CI = 0.56-0.67) compared to FBP MAC.
With our reconstruction parameters, significant differences in mean and maximum SUV values were observed. The magnitude of the mean SUV difference, however, was small. IR SAC is a promising method to accurately quantify standardized uptake values for clinical use.
Molecular Imaging & Biology 08/2002; 4(4):294-300. · 3.84 Impact Factor
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ABSTRACT: Myocardial contractile reserve and resting perfusion scintigraphy provide independent information to assess myocardial viability. The purpose of this study was to simultaneously evaluate both with (99m)Tc-sestamibi SPECT and low-dose dobutamine in canine stunning and subendocardial infarction (SEMI).
Eighteen dogs were included in the study: 7 normal, 7 stunned, and 4 with SEMI. Closed-chest stunning and SEMI were produced by angioplasty balloon occlusion of the left anterior descending artery (20 and 90 min, respectively). Subsequent radiolabeled mircospheres confirmed reflow, and (99m)Tc-sestamibi was then administered at rest. Gated SPECT and MRI tagging were performed at rest and during low-dose dobutamine infusion (5 microg/kg/min). SPECT systolic wall thickening index (SWI) and MRI radial strain quantified myocardial contraction. Postmortem 2,3,5-triphenyltetrazolium chloride staining quantified SEMI.
Defect severity by SPECT in the anterior wall was mild and was not statistically different for the stunned versus SEMI groups (P = not significant). At rest, anterior wall SPECT SWI was significantly higher in the normal versus stunned groups (21.1 +/- 3.1 vs. 10.1 +/- 9.0; P = 0.0002) and the normal versus SEMI groups (21.1 +/- 3.1 vs. 2.6 +/- 6.0; P = 0.000002). With low-dose dobutamine, SWI increased significantly compared with rest for the stunned group (29.1 +/- 10.4 vs. 10.1 +/- 9.0; P = 0.000007) but did not increase significantly for the SEMI group (11.0 +/- 11.3 vs. 2.6 +/- 6.0; P = 0.09); SWI during low-dose dobutamine infusion for the stunned group was comparable to that for the normal group (29.1 +/- 10.4 vs. 28.2 +/- 7.0; P = 0.80). SWI also showed correlation with MRI radial strain (r = 0.42; P = 0.00015).
Defect severity for stunned myocardium and SEMI was mild and was not significantly different. Contractile reserve was significantly different in stunned myocardium and SEMI. (99m)Tc-Sestamibi SPECT at rest and with low-dose dobutamine is a promising new technique to simultaneously assess myocardial perfusion and contractile reserve.
Journal of Nuclear Medicine 05/2002; 43(4):540-50. · 6.38 Impact Factor
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ABSTRACT: To assess the value of an intravascular, albumin-targeted contrast agent, MS-325, in visualizing myocardial ischemia with magnetic resonance imaging (MRI). MATERIALS and
Left anterior descending coronary artery (LAD) stenosis was created in 19 pigs using a closed-chest modified angioplasty technique. Myocardial ischemia was detected by first-pass, contrast-enhanced MRI at peak dipyridamole stress and was compared to Technetium-99m (Tc-99m) sestamibi single photon emission computed tomography (SPECT). Regional coronary blood flow was determined using microspheres.
Inducible myocardial ischemia with >40% reduction in stress myocardial blood flow was created in eight animals. An MRI defect, classified as > or=75% reduction in peak myocardial signal intensity in the affected territory, was detected in 92.3% of these animals. In the presence of mild coronary stenosis, there was uniform enhancement with MRI and tracer uptake by SPECT. Concordance of MRI and SPECT for detecting perfusion defects was 85%.
The pattern of prolonged and persistent MR hypoenhancement of the ischemic myocardial bed using MS-325, which is retained primarily in the vascular bed due to its albumin-binding properties, facilitates the detection of myocardial perfusion defects.
Journal of Magnetic Resonance Imaging 03/2002; 15(2):149-58. · 2.70 Impact Factor
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ABSTRACT: The purpose of this study was to determine the frequency of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake in the intercostal respiratory muscles (ICM) of smokers versus nonsmokers using positron emission tomography (PET).
Ninety-six whole-body PET/computed tomography (CT) scans were retrospectively reviewed; 61 studies were from smokers and 35 from nonsmokers. The ICM uptake from the lung apices to the level of the carina was visually scored with respect to FDG intensity as follows: 0 = uptake less than or equal to lung uptake; 1 = greater than lung, but less than mediastinal blood pool; 2 = equal to mediastinal blood pool; and 3 = greater than mediastinal blood pool.
In smokers, 30 out of 61 (49.2%) PET/CT scans had uptake that localized to ICM, compared to 3/35 (8.6%) studies in nonsmokers. Average ICM uptake was significantly different between smokers and nonsmokers (0.787 +/- 0.933 and 0.143 +/- 0.494, respectively; P < 0.01).
Increased FDG uptake in ICM is a physiologic pattern of uptake that is frequently seen and is more common in smokers.
Molecular Imaging & Biology 6(6):405-10. · 3.84 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Molecular Imaging & Biology 5(2):57-64. · 3.84 Impact Factor
