Single-photon Emission Computed Tomography Signal Research Articles

99mTc /SPIO-loaded polymeric micelles as MRI and SPECT imaging, cancer-targeted nanoprobe for liver cancer detection

Magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) imaging are combined to diagnose cancer with high physiological, anatomical, and metabolism sensitivity. For targeting hepatoma carcinoma, a drug delivery system is employed to carry drugs or chemicals to a specific area. Galactose is one of the sugar molecules which can be bound and increase uptake with asialoglycoprotein receptor (ASGP-R). In this study, superparamagnetic iron oxide nanoparticles (SPIONs), Galactose-functionalized poly(ethylene glycol)-block-poly(lactic acid) (Gal-PEG-b-PLA) and Diethylenetriaminepentaacetic acid-functionalized poly(ethylene glycol)-block-poly(lactic acid) (DTPA-PEG-b-PLA) were successfully synthesized and constructed to DTPA/Gal/SPIO micelles (targeting micelles) and DTPA/Met/SPIO micelles (non-targeting micelles). Technetium-99 m (99mTc) formed a complex with DTPA on the micelles as 99mTc/Gal/SPIO micelles by using stannous chloride and the pH was adjusted to acidic condition. The sizes of DTPA/Gal/SPIO micelles and DTPA/Met/SPIO micelles were lower than 100 nm with a spherical shape. In vitro study with HepG2-and L929-incubated micelles showed the intensity of blue staining of Prussian blue related to the amount of SPIO. 99mTc/Gal/SPIO micelles incubated with HepG2 exhibited signal intensity (SPECT signal) and relative R2* (MRI signal) higher than 99mTc/Met/SPIO micelles at the same time. According to these results, 99mTc-labeled Galactose-functionalized SPIO micelles have the potential for specific targeting to HepG2 and can aid in the diagnosis of cancer with MRI and SPECT dual imaging.

Radioisotope and anticancer agent incorporated layered double hydroxide for tumor targeting theranostic nanomedicine

Theranostic nanomedicine was successfully prepared using layered double hydroxide (LDH). By means of step-by-step incorporation of an anticancer drug, methotrexate (MTX), and a radioisotope, Co-57, into the interlayer space and lattice of LDH, respectively, theranostic hybrid Nanomedicine could be prepared. X-ray diffractometry, scanning electron microscopy, X-ray adsorption spectroscopy, and Fourier-transform infrared spectroscopy systematically showed that incorporating the Co2+ into the MTX-LDH did not alter the crystalline phase, size, morphology, or intact structure of the hybrid. The labeled Co-57 in MTX-LDH was highly stable in human serum, showing almost 90% retention after 48 h. In vitro cellular uptake of Co-57-labeled MTX-LDH was very high in mouse colon carcinoma CT-26 cells, with ~60 ID% at 4 h. The cytotoxicity assay of MTX-LDH showed high cancer-cell suppression on CT-26 cells. To evaluate the diagnostic ability of Co-57-labeled MTX-LDH, in vivo single-photon emission computed tomography (SPECT) images were investigated on CT-26 xenografted mouse model. The SPECT signal in tumor tissue began to appear within 1 h, and it increased for 3 h.

Single-Photon Emission Computed Tomography/Computed Tomography Imaging in a Rabbit Model of Emphysema Reveals Ongoing Apoptosis In Vivo.

Evaluation of lung disease is limited by the inability to visualize ongoing pathological processes. Molecular imaging that targets cellular processes related to disease pathogenesis has the potential to assess disease activity over time to allow intervention before lung destruction. Because apoptosis is a critical component of lung damage in emphysema, a functional imaging approach was taken to determine if targeting apoptosis in a smoke exposure model would allow the quantification of early lung damage in vivo. Rabbits were exposed to cigarette smoke for 4 or 16 weeks and underwent single-photon emission computed tomography/computed tomography scanning using technetium-99m-rhAnnexin V-128. Imaging results were correlated with ex vivo tissue analysis to validate the presence of lung destruction and apoptosis. Lung computed tomography scans of long-term smoke-exposed rabbits exhibit anatomical similarities to human emphysema, with increased lung volumes compared with controls. Morphometry on lung tissue confirmed increased mean linear intercept and destructive index at 16 weeks of smoke exposure and compliance measurements documented physiological changes of emphysema. Tissue and lavage analysis displayed the hallmarks of smoke exposure, including increased tissue cellularity and protease activity. Technetium-99m-rhAnnexin V-128 single-photon emission computed tomography signal was increased after smoke exposure at 4 and 16 weeks, with confirmation of increased apoptosis through terminal deoxynucleotidyl transferase dUTP nick end labeling staining and increased tissue neutral sphingomyelinase activity in the tissue. These studies not only describe a novel emphysema model for use with future therapeutic applications, but, most importantly, also characterize a promising imaging modality that identifies ongoing destructive cellular processes within the lung.

Distinct spatiotemporal patterns for disease duration and stage in Parkinson's disease.

To assess correlations between the degree of dopaminergic depletion measured using single-photon emission computed tomography (SPECT) and different clinical parameters of disease progression in Parkinson's disease (PD). This retrospective study included 970 consecutive patients undergoing (123)I-ioflupane SPECT scans in our institution between 2003 and 2013, from which we selected a study population of 411 patients according to their clinical diagnosis: 301 patients with PD (69.4 ± 11.0 years, of age, 163 men) and 110 patients with nondegenerative conditions included as controls (72.7 ± 8.0 years of age, 55 men). Comprehensive and operator-independent data analysis included spatial normalization into standard space, estimation of the mean uptake values in the striatum (caudate nucleus + putamen) and voxel-wise correlation between SPECT signal intensity and disease stage as well as disease duration in order to investigate the spatiotemporal pattern of the dopaminergic nigrostriatal degeneration. To compensate for potential interactions between disease stage and disease duration, one parameter was used as nonexplanatory coregressor for the other. Increasing disease stage was associated with an exponential decrease in (123)I-ioflupane uptake (R(2) = 0.1501) particularly in the head of the ipsilateral caudate nucleus (p < 0.0001), whereas increasing disease duration was associated with a linear decrease in (123)I-ioflupane uptake (p < 0.0001; R(2) = 0.1532) particularly in the contralateral anterior putamen (p < 0.0001). We observed two distinct spatiotemporal patterns of posterior to anterior dopaminergic depletion associated with disease stage and disease duration in patients with PD. The developed operator-independent reference database of 411 (123)I-ioflupane SPECT scans can be used for clinical and research applications.

Implications of CT noise and artifacts for quantitative 99mTc SPECT/CT imaging

This paper evaluates the effects of computed tomography (CT) image noise and artifacts on quantitative single-photon emission computed-tomography (SPECT) imaging, with the aim of establishing an appropriate range of CT acquisition parameters for low-dose protocols with respect to accurate SPECT attenuation correction (AC). SPECT images of two geometric and one anthropomorphic phantom were reconstructed iteratively using CT scans acquired at a range of dose levels (CTDIvol = 0.4 to 46 mGy). Resultant SPECT image quality was evaluated by comparing mean signal, background noise, and artifacts to SPECT images reconstructed using the highest dose CT for AC. Noise injection was performed on linear-attenuation (μ) maps to determine the CT noise threshold for accurate AC. High levels of CT noise (σ ∼ 200-400 HU) resulted in low μ-maps noise (σ ∼ 1%-3%). Noise levels greater than ∼ 10% in 140 keV μ-maps were required to produce visibly perceptible increases of ∼ 15% in (99m)Tc SPECT images. These noise levels would be achieved at low CT dose levels (CTDIvol = 4 μGy) that are over 2 orders of magnitude lower than the minimum dose for diagnostic CT scanners. CT noise could also lower (bias) the expected μ values. The relative error in reconstructed SPECT signal trended linearly with the relative shift in μ. SPECT signal was, on average, underestimated in regions corresponding with beam-hardening artifacts in CT images. Any process that has the potential to change the CT number of a region by ∼ 100 HU (e.g., misregistration between CT images and SPECT images due to motion, the presence of contrast in CT images) could introduce errors in μ140 keV on the order of 10%, that in turn, could introduce errors on the order of ∼ 10% into the reconstructed (99m)Tc SPECT image. The impact of CT noise on SPECT noise was demonstrated to be negligible for clinically achievable CT parameters. Because CT dose levels that affect SPECT quantification is low (CTDIvol ∼ 4 μGy), the low dose limit for the CT exam as part of SPECT/CT will be guided by CT image quality requirements for anatomical localization and artifact reduction. A CT technique with higher kVp in combination with lower mAs is recommended when low-dose CT images are used for AC to minimize beam-hardening artifacts.

Pulp Cell Tracking by Radionuclide Imaging for Dental Tissue Engineering

Pulp engineering with dental mesenchymal stem cells is a promising therapy for injured teeth. An important point is to determine the fate of implanted cells in the pulp over time and particularly during the early phase following implantation. Indeed, the potential engraftment of the implanted cells in other organs has to be assessed, in particular, to evaluate the risk of inducing ectopic mineralization. In this study, our aim was to follow by nuclear imaging the radiolabeled pulp cells after implantation in the rat emptied pulp chamber. For that purpose, indium-111-oxine (¹¹¹In-oxine)-labeled rat pulp cells were added to polymerizing type I collagen hydrogel to obtain a pulp equivalent. This scaffold was implanted in the emptied pulp chamber space in the upper first rat molar. Labeled cells were then tracked during 3 weeks by helical single-photon emission computed tomography (SPECT)/computed tomography performed on a dual modality dedicated small animal camera. Negative controls were performed using lysed radiolabeled cells obtained in a hypotonic solution. In vitro data indicated that ¹¹¹In-oxine labeling did not affect cell viability and proliferation. In vivo experiments allowed a noninvasive longitudinal follow-up of implanted living cells for at least 3 weeks and indicated that SPECT signal intensity was related to implanted cell integrity. Notably, there was no detectable systemic release of implanted cells from the tooth. In addition, histological analysis of the samples showed mitotically active fibroblastic cells as well as neoangiogenesis and nervous fibers in pulp equivalents seeded with entire cells, whereas pulp equivalents prepared from lysed cells were devoid of cell colonization. In conclusion, our study demonstrates that efficient labeling of pulp cells can be achieved and, for the first time, that these cells can be followed up after implantation in the tooth by nuclear imaging. Furthermore, it appears that grafted cells retained the label and are viable to follow the repair process. This technique is expected to be of major interest for monitoring implanted cells in innovative therapies for injured teeth.

Switching to Sulphonylureas in Children With iDEND Syndrome Caused by KCNJ11 Mutations Results in Improved Cerebellar Perfusion

OBJECTIVEActivating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit of the KATP channel, result in permanent neonatal diabetes mellitus. They also may cause neurologic symptoms such as mental retardation and motor problems (iDEND syndrome) and epilepsy (DEND syndrome). Sulphonylurea (SU) treatment is reported to alleviate both the neurologic symptoms and diabetes in such cases. The study aimed to establish the magnitude and functional basis of the effect of SUs on the neurologic phenotype in children with iDEND using neuroimaging before and after insulin replacement with glibenclamide.RESEARCH DESIGN AND METHODSTo localize and quantify the effect of glibenclamide administration, we performed single-photon emission computed tomography in seven patients with different mutations in KCNJ11. In five patients, measurements before and after initiation of SU treatment were performed.RESULTSSignificant changes in single-photon emission computed tomography signal intensity after transfer to SU therapy were restricted to the cerebellum, consistent with previous data showing high Kir6.2 expression in this brain region. Cerebellar perfusion improved for both left (P = 0.006) and right (P = 0.01) hemispheres, with the mean improvement being 26.7 ± 7.1% (n = 5). No patients showed deterioration of cerebellar perfusion on SU therapy. Electrophysiological studies revealed a good correlation between the magnitude of KATP channel dysfunction and the clinical phenotype; mutant channels with the greatest reduction in adenosine 5′-triphosphate inhibition were associated with the most severe neurologic symptoms.CONCLUSIONSWe conclude it is likely that at least some of the beneficial effects of SU treatment on neurodevelopment in iDEND patients result from improved cerebellar perfusion.

Changes of dopamine transporter function in striatum during acute morphine addiction and its abstinence in rhesus monkey

Although dopamine transporter (DAT) is essential for addiction, the effect of additive drugs on DAT function is still controversial, especially for opiates. We investigated the functional changes of dopamine transporter in striatum of rhesus monkeys during acute morphine injection and its abstinence. Four rhesus monkeys, 6 to 9 years old, two male and two female, were examined for 12 days. Single photon emission computed tomography (SPECT) was performed with (99)T(cm)-TRODAT-1 as the radiopharmaceutical dopamine transporter agent during different stages of acute morphine injection and its abstinence. The ratios of SPECT signal between striatum and cerebellum (ST/CB) were calculated. The ST/CB ratio declined significantly on the first day of morphine injection and continued declining with more morphine injections. After abstinence, the ratio increased with time, but was still significantly lower on the 5th day of abstinence than the normal level. In rhesus monkey, acute morphine injection has both rapid and lasting effects on DAT by downregulating its function. The decline was partially reversible following morphine abstinence. The results suggest that striatum is one effective target of morphine and that the DAT function in striatum is one indicator for morphine addiction.

Astrocytes as a predominant cellular site of (99m)Tc-HMPAO retention.

Technetium-99m-d,l-hexamethylpropylene amine oxime ((99m)Tc-HMPAO) retention in the brain monitored by single photon emission computed tomography (SPECT) is currently used as a marker of cerebral blood flow. The purported mechanism by which (99m)Tc-HMPAO accumulates in the brain is through its intracellular conversion from a lipophilic form to more hydrophilic derivatives within the brain parenchyma. The issue of the contribution of different cell types on (99m)Tc-HMPAO retention was investigated in vitro by studying the accumulation of (99m)Tc-HMPAO in primary cultures of mouse cortical astrocytes and neurons. Results show that (99m)Tc-HMPAO retention predominates in astrocytes over neurons by a factor of approximately 2.5 (0.26 +/- 0.05 vs. 0.095 +/- 0.042 fmol/mg protein after 120 minutes, respectively). Diethyl maleate (60 micromol/L), ethacrynic acid (1 mmol/L) and buthionine sulfoximine (1 mmol/L), 3 agents which significantly reduced glutathione levels also decreased (99m)Tc-HMPAO retention in both astrocytes (29%, 3%, and 46% of control, respectively) and neurons (69%, 11% and 63% of control). Decrease did not always correlate with glutathione levels, however, which suggests that other factors could be involved. The possibility that cell energy status determines (99m)Tc-HMPAO retention was also assessed. Agents that activate (glutamate, azide) or inhibit (cytochalasin B) glucose utilization in astrocytes, as measured by the (3)H-2-deoxyglucose method, were without effect on (99m)Tc-HMPAO retention. In conclusion, the data presented indicate that astrocytes may constitute a prominent site of (99m)Tc-HMPAO retention and most likely contribute significantly to the SPECT signal. In addition, the data also suggest that specific alterations in glial cell metabolism could explain flow-independent changes in (99m)Tc-HMPAO retention in the brain as observed by SPECT in some pathologies.