Evaluating performance of a pixel array semiconductor SPECT system

Objectives: Small animal imaging has recently been focused on basic nuclear medicine. We have designed and built a small animal SPECT imaging system using a semiconductor camera and a newly designed collimator. We assess the performance of this system for small object imaging. Methods: We employed an MGC1500 (Acrorad Co.) camera including a CdTe semiconductor. The pixel size was 1.4 mm/pixel. We designed and produced a parallel-hole collimator with 20-mm hole length. Our SPECT system consisted of a semiconductor camera with the subject holder set on an electric rotating stage controlled by a computer. We compared this system with a conventional small animal SPECT system comprising a SPECT-2000H scanner with four Anger type cameras and pinhole collimators. The count rate linearity for estimation of the scatter was evaluated for a piechart phantom containing different concentrations of 99mTc. We measured the FWHM of the 99mTc SPECT line source along with scatter. The system volume sensitivity was examined using a flood source phantom which was 35 mm long with a 32-mm inside diameter. Additionally, an in vivo myocardial perfusion SPECT study was performed with a rat. Results: With regards to energy resolution, the semiconductor camera (5.6%) was superior to the conventional Anger type camera (9.8%). In the count rate linearity evaluation, the regression lines of the SPECT values were y = 0.019x + 0.031 (r2 = 0.999) for our system and y = 0.018x + 0.060 (r2 = 0.997) for the conventional system. Thus, the scatter count using the semiconductor camera was less than that using the conventional camera. FWHMs of our system and the conventional system were 2.9 ± 0.1 and 2.0 ± 0.1 mm, respectively. Moreover, the system volume sensitivity of our system [0.51 kcps/(MBq/ ml)/cm] was superior to that of the conventional system [0.44 kcps/(MBq/ml)/cm]. Our system provided clear images of the rat myocardium, sufficient for practical use in small animal imaging. Conclusions: Our SPECT system, utilizing a semiconductor camera, permits high quantitative analysis by virtue of its low scatter radiation and high sensitivity. Therefore, this system may contribute to molecular imaging of small animals and basic medical research

Prolonged High-Fat Feeding Enhances Aortic 18F-FDG and 99mTc-Annexin A5 Uptake in Apolipoprotein E-Deficient and Wild-Type C57BL/6J Mice

18F-FDG, a marker of the enhanced metabolism characteristic of activated inflammatory cells, and 99mTc-annexin A5, a marker of apoptosis, are both widely believed to be useful for the imaging of unstable atheroma (rupture-prone vulnerable plaques [VP]). Serum cholesterol functions as a proinflammatory factor, driving the formation of VP, and affects the immune responses of aortic tissues systemically. It is therefore reasonable to postulate that prolonged cholesterol loading may alter the aortic uptake of these tracers. Here, we evaluated the aortic uptake of 18F-FDG and 99mTc-annexin A5 in apolipoprotein E-deficient (apoE2/2) and wild-type mice placed on high-fat diets. Methods: Male apoE2/2 and wild-type (C57BL/6J) mice were maintained on high-fat diets after the age of 5 wk. Wild-type mice fed regular chow were used as controls. At the ages of 10, 18, and 25 wk (5–15 mice per group at each time point), mice were injected with 18F-FDG or 99mTc-annexin A5 after 12 h of fasting. At 1 h after 18F-FDG injection (or 2 h after 99mTc-annexin A5 injection), mice were sacrificed, and the aortas were removed for welltype scintillation counting of radioactivity. The results were expressed as percentage injected dose per gram of tissue and normalized by animal body weight [(ID%/g) · kg]. En face staining was then performed to assess the location and size (surface area) of the lipid pool within each aortic specimen. Concurrent blood samples were obtained to determine the plasma lipid profile of each group. Results: No atherosclerotic lesions were found in wild-type mice regardless of the diet, whereas the lesion area progressively increased with age in apoE2/2 mice. Mean plasma cholesterol levels remained stable with the regular diet in wild-type mice (73–78 mg/dL) but increased with cholesterol feeding in wild-type mice (143–179 mg/dL) and in apoE2/2 mice (.1,300 mg/dL). Aortic tracer uptake [(ID%/g) · kg] remained stable with the regular diet in wild-type mice (0.054– 0.053 and 0.021–0.023 for 99mTc-annexin A5) but increased with cholesterol feeding in wild-type mice (0.164 for 18F-FDG and 0.036 for 99mTc-annexin A5 at 25 wk) and in apoE2/2 mice (0.249 for 18F-FDG and 0.047 for 99mTc-annexin A5 at 25 wk). Conclusion: The accumulation of 18F-FDG and 99mTc-annexin A5 in aortic tissues is influenced not only by the progression of atherosclerotic disease but also by cholesterol loading over time

Performance characterization of the Inveon preclinical small-animal PET/SPECT/CT system for multimodality imaging

Purpose: We analyzed the performance of the Inveon for an integrated small-animal PET/SPECT/CT system and compared the imaging capabilities of the SPECT and the PET components. Methods: For SPECT, energy resolution, tomographic spatial resolution, and system sensitivity were evaluated with 99mTc solution using a single pinhole collimator. For PET, spatial resolution, absolute sensitivity, scatter fraction, and peak noise equivalent count (NEC) were evaluated. A micro-Derenzo phantom, cylindrical phantom, and National Electrical Manufacturers Association NU-4 image quality phantom were scanned to compare SPECT and PET image capabilities, and SPECT and PET bone imaging were performed on a normal rat in vivo. Results: SPECT spatial resolution was 0.84 mm full width at half maximum (FWHM) at a radius of rotation of 25 mm using the 0.5-mm pinhole aperture collimator, while PET spatial resolution was 1.63 mm FWHM at the center. SPECT system sensitivity at a radius of rotation of 25 mm was 35.3 cps/MBq (4 × 10^[-3]%) using 0.5-mm pinhole aperture, while PET absolute sensitivity was 3.2% for 350-650 keV and 3.432 ns. Accordingly, the volume sensitivity of PET was three orders of magnitude higher than that of SPECT. Conclusions: This integrated PET/SPECT/CT system provided high system performance with excellent spatial resolution for SPECT and sensitivity for PET. Based on tracer availability and system performance, SPECT and PET have complementary roles for multi-modality small-animal imaging

An ultra-high-energy collimator for small animal imaging in dual-isotope study of 18F and 99mTc

We have developed a pinhole collimator for small animal imaging using dual-isotopes, such as gamma and positron emitters. A lead cylinder containing a pinhole was placed around the subject (a small animal). The cylinder was equipped with a non-collimator gamma camera, and dual-isotope (99mTc-MIBI and 18F-FDG) SPECT was performed on a Wistar King Aptekman/hok (WKAH) rat. System planar sensitivity and Full-Width at Half-Maximum (FWHM) were measured for each radionuclide. System planar sensitivities for 99mTc and 18F SPECT were 2 and 7 cps/MBq, respectively. FWHMs for 99mTc and 18F SPECT were 2.0±0.5 and 2.7±0.5 mm, respectively. The collimator is relatively light (23 kg), and thus SPECT projection data could be acquired by rotating the gamma camera while the object remained stationary. The pinhole collimator can be used with a conventional rotating gamma camera. The present study demonstrated that it is possible to image organs in vivo in sufficient detail using the newly developed pinhole collimator. Further refinements to the experimental procedure may provide simultaneous high-resolution imaging of small animals using positron and gamma emitters with this collimator

Dynamic 11C-methionine PET analysis has an additional value for differentiating malignant tumors from granulomas : an experimental study using small animal PET

Purpose: We evaluated whether the dynamic profile of 11C-MET may have an additional value in differentiating malignant tumors from granulomas in experimental rat models by small animal PET. Methods: Rhodococcus aurantiacus and allogenic rat C6-glioma cells were inoculated respectively into the right and left calf muscles to generate a rat model bearing both granulomas and tumors (n = 6). Ten days after the inoculations, dynamic 11C-MET PET was performed by small-animal PET up to 120 min after injection of 11C-MET. The next day, after overnight fasting, the rats were injected with 18F-FDG, and dynamic 18F-FDG PET was performed up to 180 min. The time-activity curves, static images, and mean standardized uptake value (SUV) in the lesions were calculated. Results: 11C-MET uptake in the granuloma showed a slow exponential clearance after an initial distribution, while the uptake in the tumor gradually increased with time. The dynamic pattern of 11C-MET uptake in the granuloma was significantly different from that in the tumor (p < 0.001). In the static analysis of 11C-MET, visual assessment and SUV analysis could not differentiate the tumor from the granuloma in all cases, although the mean SUV in the granuloma (1.48 ± 0.09) was significantly lower than that in the tumor (1.72 ± 0.18, p < 0.01). The dynamic patterns, static images, and mean SUVs of 18F-FDG in the granuloma were similar to those in the tumor (p = NS). Conclusions: Dynamic 11C-MET PET has an additional value for differentiating malignant tumors from granulomatous lesions, which deserve further elucidation in clinical settings

Comparison of 99mTc-annexin A5 with 18F-FDG for detecting atherosclerosis in ApoE-/- mice

Purpose: 99mTc-annexin A5, a marker of ongoing apoptosis, and 18F-FDG, a marker of the increased metabolism of inflammatory cells, are supposed to be useful in the detection of metabolically active atheroma. This study reports a comparison of the intralesional distribution of these tracers in relation to lesion development in ApoE−/− mice. Methods: Male ApoE−/− mice (n = 12–14/group) were maintained on a Western-type diet after the age of 5 weeks. At 25 weeks, 99mTc-annexin A5 or 18F-FDG was injected and the aortas were harvested for autoradiography (ARG) and Oil Red O staining. Regional radioactivity accumulation was compared in relation to the Oil Red O staining score (ranging from 0 to 3, a semiquantitative parameter for evaluating lesion development). Results: Both 99mTc-annexin A5 and 18F-FDG showed preferential uptake into atherosclerotic lesions, with higher uptake levels for 18F-FDG (mean, 56.07 %ID×kg/m2) than for 99mTc-annexin A5 (mean, 10.38 %ID×kg/m2). The regional uptake levels of each tracer correlated with the Oil Red O staining score (r = 0.65, p 0.5) to early lesions (score <0.5) were significantly higher for 99mTc-annexin A5 than for 18F-FDG (f = 4.73, p = 0.03). Conclusion: Both 99mTc-annexin A5 and 18F-FDG accumulate in atherosclerotic lesions and correlate with the severity of each lesion. The higher absolute uptake levels of 18F-FDG may be advantageous for lesion detection, whereas the preferential uptake of 99mTc-annexin A5 in advanced lesions may be a useful indicator of late-stage lesions or vulnerable plaque transformation

Effects of feeding condition on the myocardial and hepatic accumulation of radioiodine-labeled BMIPP in mice

Objective I-123-15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid ([I-123]BMIPP), a fatty acid analog, is widely used for the diagnosis of cardiac diseases. Feeding condition is one of the important factors in the myocardial fatty acid uptake, which may also affect myocardial accumulation of [I-123]BMIPP and image quality of [I-123]BMIPP scintigraphy. However, the relationship between the myocardial accumulation of [I-123]BMIPP and the feeding condition is not entirely clear. Therefore, we determined the myocardial accumulation of [I-125]BMIPP in mice at various metabolic statuses induced by fasting in comparison with the hepatic accumulation. Methods Fed or fasted (6-, 12-, and 24-h fasted) mice were intravenously injected with [I-125]BMIPP (35.2-75.0 kBq, 4 nmol). Radioactivities in the heart and liver were measured at 1, 5, 10, 30, 60, and 120 min after the injection (n = 5-15/time point for each group), and then, the heart-to-liver (H/L) ratios were calculated. Results The myocardial accumulation level of [I-125]BMIPP in the fed group was almost the same as that in the 6-h-fasted group at each time point, although it was decreased by 12- and 24-h fasting. The H/L ratios of [I-125]BMIPP accumulation level were significantly decreased by fasting (1.92 +/- 0.22, 1.45 +/- 0.13, 1.12 +/- 0.13, and 0.91 +/- 0.15 at 10 min, and 3.30 +/- 0.62, 2.09 +/- 0.35, 1.79 +/- 0.34, and 1.27 +/- 0.06 at 30 min after the injection, respectively, for the fed group and the 6-, 12-, and 24-h-fasted groups;p < 0.0001), largely owing to the increase in the hepatic accumulation level in the fasting groups. Conclusion Although short-period (6 h) fasting did not affect the myocardial accumulation level of [I-125]BMIPP, the hepatic accumulation level was increased. The present results indicate that the fed condition may provide higher-contrast images in myocardial [I-123]BMIPP scintigraphy

Monitoring tumor proliferative response to radiotherapy using F-18-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67

Although radiotherapy is an important treatment strategy for head and neck cancers, it induces tumor repopulation which adversely affects therapeutic outcome. In this regard, fractionated radiotherapy is widely applied to prevent tumor repopulation. Evaluation of tumor proliferative activity using F-18-fluorothymidine (FLT), a noninvasive marker of tumor proliferation, may be useful for determining the optimal timing of and dose in the repetitive irradiation. Thus, to assess the potentials of FLT, we evaluated the sequential changes in intratumoral proliferative activity in head and neck cancer xenografts (FaDu) using FLT. FaDu tumor xenografts were established in nude mice and assigned to control and two radiation-treated groups (10 and 20 Gy). Tumor volume was measured daily. H-3-FLT was injected intravenously 2 h before killing. Mice were killed 6, 24, 48 h, and 7 days after the radiation treatment. Intratumoral H-3-FLT level was visually and quantitatively assessed by autoradiography. Ki-67 immunohistochemistry (IHC) was performed. In radiation-treated mice, the tumor growth was significantly suppressed compared with the control group, but the tumor volume in these mice gradually increased with time. In the visual assessment, intratumoral H-3-FLT level diffusely decreased 6 h after the radiation treatment and then gradually increased with time, whereas no apparent changes were observed in Ki-67 IHC. Six hours after the radiation treatment at 10 and 20 Gy, the intratumoral H-3-FLT level markedly decreased to 45 and 40 % of the control, respectively (P < 0.0001 vs control), and then gradually increased with time. In each radiation-treated group, the H-3-FLT levels at 48 h and on day 7 were significantly higher than that at 6 h. The intratumoral H-3-FLT levels in both treated groups were 68 and 60 % at 24 h (P < 0.001), 71 and 77 % at 48 h (P < 0.001), and 83 and 81 % on day 7 (P = NS) compared with the control group. Intratumoral FLT uptake level markedly decreased at 6 h and then gradually increased with time. Sequential evaluation of intratumoral proliferative activity using FLT can be beneficial for determining the optimal timing of and dose in repetitive irradiation of head and neck cancer

Relationship between biodistribution of a novel thymidine phosphorylase (TP) imaging probe and TP expression levels in normal mice

Objective: Thymidine phosphorylase (TP) is a key enzyme in the pyrimidine nucleoside salvage pathway and its expression is upregulated in a wide variety of solid tumors. In mice, we previously observed high and specific accumulation levels of our TP imaging probe, radioiodinated 5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil (IIMU) not only in high-TP-expressing tumors, but also in the liver and small intestine. To clarify the reason for the high accumulation levels of radioiodinated IIMU in the liver and small intestine, we investigated the expression levels of TP in mice in comparison with the biodistribution of radioiodinated IIMU (123I-IIMU). Methods: BALB/cCrSlc mice were injected with 123I-IIMU, and the radioactivity levels [%ID/g (normalized to a mouse of 25 g body weight)] in the tissues of interest were determined 0.5, 1, 3 and 24 h after the injection (n = 5, each time point). To determine the expression levels of TP, BALB/cCrSlc and ddy mice (n = 3/each strain) were euthanized, and the heart, liver, lung, spleen, kidney, stomach, small intestine, large intestine and brain were collected. The mRNA and protein expression levels of TP in these organs were examined by quantitative reverse transcription-polymerase chain reaction and western blot analyses, respectively. Results: In BALB/cCrSlc mice administered 123I-IIMU, markedly high radioactivity levels were observed in the liver [1.568 ± 0.237 (%ID/g)] and small intestine [0.506 ± 0.082 (%ID/g)], whereas those in the other tissues were fairly low [<0.010 ± 0.003 (%ID/g)] 30 min after the injection. The highest expression levels of TP mRNA were also observed in the liver and small intestine among the tissues tested. Immunoblotting showed intense immunoreactive bands of the TP protein for the liver and small intestine, whereas no notable bands were detected for other tissues. Similar expression profiles of TP mRNA and protein were observed in ddy mice. Conclusion: We confirmed TP expression in various tissues of mice at the mRNA and protein levels: high TP expression levels were observed in the liver and small intestine. These high TP expression levels are consistent with the high accumulation levels of 123I-IIMU in these tissues. Our results may provide important information about the physiological accumulation of 123I-IIMU, which may be useful for the clinical diagnostic imaging of TP