Emission Computed Tomography Imaging Studies Research Articles

99mTc-D(RGD): molecular imaging probe for diagnosis of αvβ3-positive tumors.

Arginine-glycine-aspartic acid (RGD) peptide with its specific binding affinity to integrin αvβ3, is widely investigated for the development of molecular imaging probes for diagnosis of αvβ3-positive tumors. The aim of this work was to evaluate the ability of Tc- HYNIC-D(RGD), a novel retro-inverso peptidomimetic derivative for U87MG tumor (αvβ3-positive) imaging. HYNIC-D(RGD) labeled with Tc using tricine/EDDA as an exchange coligands. Single-photon emission computed tomography imaging and biodistribution study were performed in nude mice bearing U87MG xenograft tumor. The labeling yield was >95%. The radiopeptide showed high uptake value in the U87MG tumor relative to muscle after 2 hours (1.43 ± 0.05 vs. 0.22 ± 0.11 %ID/g). The tumor/muscle ratio was 6.5. Blocking experiment showed specific binding towards tumor. Single-photon emission computed tomography imaging study revealed that radiopeptide had prominent uptake in U87MG tumor. The novel Tc HYNIC- D(RGD) was demonstrated to be a useful radiotracer for the assessment of αvβ3-positive tumor in animal model. Therefore, further clinical and preclinical studies are required.

Reduced serotonin receptors and transporters in normal aging adults: a meta-analysis of PET and SPECT imaging studies

Alterations in serotonin (5-HT) function have been hypothesized to underlie a range of physiological, emotional, and cognitive changes in older age. Here, we conducted a quantitative synthesis and comparison of the effects of age on 5-HT receptors and transporters from cross-sectional positron emission tomography and single-photon emission computed tomography imaging studies. Random-effects meta-analyses of 31 studies including 1087 healthy adults yielded large negative effects of age in 5-HT-2A receptors (largest in global cortex), moderate negative effects of age in 5-HT transporters (largest in thalamus), and small negative effects of age in 5-HT-1A receptors (largest in parietal cortex). Presynaptic 5-HT-1A autoreceptors in raphe/midbrain, however, were preserved across adulthood. Adult age differences were significantly larger in 5-HT-2A receptors compared with 5-HT-1A receptors. A meta-regression showed that 5-HT target, radionuclide, and publication year significantly moderated the age effects. The findings overall identify reduced serotonergic signal transmission in healthy aging. The evidence for the relative preservation of 5-HT-1A compared with 5-HT-2A receptors may partially explain psychological age differences, such as why older adults use more emotion-focused rather than problem-focused coping strategies.

Novel 99mTc-labelled complexes with thymidine isocyanide: radiosynthesis and evaluation as potential tumor imaging tracers.

A novel thymidine isocyanide (CN-TdR) functionalized at the N3 position of thymidine was synthesized and then radiolabelled with 99mTc(i) and [99mTc(i)(CO)3]+ cores to produce [99mTc(CN-TdR)6]+ and [99mTc(CO)3(CN-TdR)3]+, respectively. Both of them were prepared with high radiochemical purity and were stable over 6 h in saline at ambient temperature and in serum at 37 °C. The partition coefficient results demonstrated that they were hydrophilic. The cell internalization studies showed that their uptake might be mediated by nucleoside transporters. Biodistribution of these complexes in mice bearing the S180 tumor showed that they accumulated in the tumor with high uptake and cleared rapidly from blood and muscles, producing high tumor/blood and tumor/muscle ratios. Between them, [99mTc(CN-TdR)6]+ exhibited advantages concerning a higher tumor uptake, tumor/blood ratio and tumor/muscle ratio at 60 min post-injection. Single photon emission computed tomography imaging studies showed that there was a clear accumulation in tumor sites, suggesting that [99mTc(CN-TdR)6]+ could be a promising candidate for tumor imaging.

Synthesis and evaluation of a novel 99mTc nitrido radiopharmaceutical with alendronate dithiocarbamate as a potential bone‐imaging agent

Currently, a popular strategy for designing novel radioprobes as bone-imaging agents is based on the concept of bifunctional radiopharmaceuticals. Considering the dithiocarbamate ligand can act as a suitable bifunctional linking agent to attach technetium-99m (99m Tc) to corresponding target molecules, in this study, alendronate dithiocarbamate (ALNDTC) was synthesized and radiolabeled with [99m Tc≡N]2+ core by ligand exchange reaction to produce 99m TcN-ALNDTC complex, for the potential use as a novel probe for bone imaging. The radiochemical purity of the complex was over 90%. The complex was stable in vitro and could bind to hydroxyapatite. The partition coefficient result indicated it was hydrophilic, and an evaluation of biodistribution in mice indicated that the complex exhibited a higher bone uptake than did 99m Tc-labeled methylenediphosphonate (99m Tc-MDP). Further, single photon emission computed tomography imaging study indicated clear accumulation in bone, suggesting that 99m TcN-ALNDTC would be a promising candidate for bone imaging.

Residual striatal dopaminergic nerve terminals in very long-standing Parkinson's disease: A single photon emission computed tomography imaging study

Molecular imaging studies of Parkinson's disease (PD) progression mostly focus on the first 5 years after disease onset, demonstrating rapid initial nigrostriatal neuronal loss. The fate of residual functional dopaminergic nerve terminals in patients with long-standing PD has not yet been specifically explored. Therefore, we performed [(123)I]-FP-CIT single photon emission computed tomography (SPECT) in 15 patients with very long-standing PD (mean disease duration 20.6 ± 6.3 years). Measurable uptake of [(123)I]-FP-CIT was still detected in the striata of all patients. As seen in early stages, reduction of tracer uptake in the putamen was more prominent than in the caudate nucleus. Asymmetry in tracer uptake between the two putamen and caudate nuclei was preserved. These findings indicate that degeneration of dopaminergic neurons in PD is not total even after many years of illness. Data should be considered in exploring underlying causes of progressive loss of nigrostriatal dopaminergic neurons and development of future novel dopaminergic therapeutic strategies in PD.

Evaluation of an 111In-Radiolabeled Peptide as a Targeting and Imaging Agent for ErbB-2 Receptor–Expressing Breast Carcinomas

The cellular targeting and tumor imaging properties of a novel ErbB-2-avid peptide, discovered from bacteriophage display, were evaluated in human breast carcinoma cells and in breast carcinoma-xenografted mice. The affinity of the ErbB-2 targeting peptide KCCYSL and its alanine substituted counterparts for the extracellular domain (ECD) of purified recombinant ErbB-2 (ErbB-2-ECD) was assessed by fluorescence titration. Binding of the KCCYSL peptide to breast and prostate carcinoma cells was analyzed by confocal microscopy. A DOTA(GSG)-KCCYSL peptide conjugate was radiolabeled with 111In, and stability, target binding, and internalization were analyzed in vitro. In vivo biodistribution and single-photon emission computed tomography imaging studies were done with the radiolabeled peptide in MDA-MB-435 human breast tumor-bearing severe combined immunodeficient mice. KCCYSL peptide exhibited high affinity (295 +/- 56 nmol/L) to ErbB-2-ECD. Substitution of alanine for lysine, tryptophan, and cysteine reduced the peptide affinity approximately 1- to 2.4-fold, whereas replacing leucine completely abolished binding. Both biotin-KCCYSL and 111In-DOTA(GSG)-KCCYSL were capable of binding ErbB-2-expressing human breast carcinoma cells in vitro. Approximately 11% of the total bound radioactivity was internalized in the carcinoma cells. Competitive binding studies indicated that the radiolabeled peptide exhibited an IC(50) value of 42.5 +/- 2.76 nmol/L for the breast carcinoma cells. 111In-DOTA(GSG)-KCCYSL was stable in serum and exhibited rapid tumor uptake (2.12 +/- 0.32 %ID/g) at 15 min postinjection and extended retention coupled with rapid whole body disappearance, as observed by biodistribution and single-photon emission computed tomography imaging studies, respectively. The DOTA(GSG)-KCCYSL peptide has the potential to be used as a tumor-imaging agent and a vehicle for specific delivery of radionuclide or cytotoxic agents for tumors overexpressing ErbB-2.

SPECT myocardial perfusion imaging in morbidly obese patients: Image quality, hemodynamic response to pharmacologic stress, and diagnostic and prognostic value

Obesity is a growing epidemic in the United States, and little is known about the characteristics of the morbidly obese population (body mass index [BMI] > or = 40 kg/m2) undergoing stress myocardial perfusion imaging (MPI). We retrospectively reviewed all consecutive morbidly obese patients without known coronary artery disease presenting for a clinically indicated technetium 99m (Tc-99m) gated stress single photon emission computed tomography imaging study over a 42-month period. Studies were analyzed for image quality, for the contribution of attenuation correction to image interpretation, and for the hemodynamic response to pharmacologic stress. In patients who subsequently had cardiac catheterization, the results were compared with those from the initial MPI study, and the Social Security Death Index and hospital medical records were searched to the assess survival rate in the entire cohort. A total of 433 patients were identified with a mean BMI of 47.3 +/- 8 kg/m2 and a mean Tc-99m stress dose of 35.6 +/- 5.4 mCi. Image quality was good in 61% of the patients, adequate in 37%, and poor in 2%. It was found to be dependent on the stressor used (better with exercise) but did not correlate with increasing weight or BMI. Attenuation correction was used in 95% of the studies reviewed and was helpful for image interpretation in 60%. The heart rate response to dipyridamole and adenosine was more pronounced and the blood pressure response to dipyridamole was less pronounced in morbidly obese patients compared with nonobese control patients. In the 43 patients who underwent catheterization, stress MPI had a sensitivity of 95% and negative predictive value of 80%. Kaplan-Meier survival analysis at 1 year showed a significant difference in survival rate of 98.3% for normal MPI studies and 94.0% for abnormal MPI studies (P = .02). Diagnostic-quality single photon emission computed tomography imaging is feasible in the majority (98%) of morbidly obese patients with the use of a dual-head camera, attenuation correction, and high stress Tc-99m tracer doses. Exercise stress was associated with better image quality. The prognostic value of a normal MPI study in this population appears to be less favorable than in non-morbidly obese patients.

Effect of Platelet-Derived Growth Factor Receptor-β Inhibition with STI571 on Radioimmunotherapy

Whereas radioimmunotherapy of hematologic malignancies has evolved into a viable treatment option, the responses of solid tumors to radioimmunotherapy are discouraging. The likely cause of this problem is the interstitial hypertension inherent to all solid tumors. Remarkable improvements in tumor responses to radioimmunotherapy were discovered after the inclusion of STI571 in the therapy regimen. A combination of the tumor stroma-reactive STI571, a potent platelet-derived growth factor receptor-beta (PDGFr-beta) antagonist, and the tumor-seeking radiolabeled antibody B72.3 yielded long-lasting growth arrest of the human colorectal adenocarcinoma LS174T grown as s.c. xenografts in athymic mice. The interaction of STI571 with the stromal PDGFr-beta reduced tumor interstitial fluid pressure (P(IF)) by >50% and in so doing improved the uptake of B72.3. The attenuation of P(IF) also had a positive effect on the homogeneity of antibody distribution. These effects were dose-dependent and under optimized dosing conditions allowed for a 2.45 times increase in the tumor uptake of B72.3 as determined in the biodistribution studies. Single-photon emission computed tomography imaging studies substantiated these results and indicated that the homogeneity of the radioisotope distribution was also much improved when compared with the control mice. The increased uptake of radioimmunotherapy into the tumor resulted in >400% increase in the tumor absorbed radiation doses in STI571 + radioimmunotherapy-treated mice compared with PBS + radioimmunotherapy-treated mice. The improved antibody uptake in response to the attenuation of tumor P(IF) was identified as the primary reason for the growth arrest of the STI571 + radioimmunotherapy-treated tumors. Two related causes were also identified: (a) the improved homogeneity of monoclonal antibody distribution in tumor and (b) the increased tumor radiosensitivity resulting from the improved tumor oxygenation.

Cerebral Blood Flow Effects of Pain and Acupuncture: A Preliminary Single-Photon Emission Computed Tomography Imaging Study

Background. The purpose of this study was to investigate the cerebral blood flow changes associated with the analgesic effect of acupuncture in patients with chronic pain. Methods. Seven patients presenting with a chronic pain syndrome and 5 healthy controls were included. All single-photon emission com puted tomography (SPECT) scans were acquired with a uniform protocol. The patient group was injected with the radioisotope hexamethyl propyleneamine oxime (HMPAO) while experienc ing their usual level of pain. A baseline scan was acquired approximately 20 minutes after administration of the HMPAO. The patient then underwent acupuncture therapy with needles placed in points specifically selected to relieve pain. When the pain improved, as determined by a 10-digit score for pain assessment, the patient was reinjected with HMPAO and imaged 20 minutes later for the acupuncture scan. The refer ence group also had a baseline and acupuncture scan, although the acupuncture itself was performed using a stan dardized set of needle points. Results. The reference group par ticipants were found to have significant increases in the thalamic and prefrontal cortex activity on the acupuncture scan compared to the baseline. The baseline scans of the pain patients showed significant asymmetric uptake in the thalami compared to controls. This asymmetry reversed or normalized after the acupuncture therapy. Significant correlations were observed between the change of activity in the prefrontal cortex and ipsilateral sensorimotor area. Conclusion. The results from these cases show that HMPAO-SPECT is capable of detecting changes in cerebral blood flow associated with pain and that acupuncture analgesia is associated with changes in the activity of the frontal lobes, brain stem, and thalami.

Cerebral Blood Flow Effects of Pain and Acupuncture: A Preliminary Single-Photon Emission Computed Tomography Imaging Study

The purpose of this study was to investigate the cerebral blood flow changes associated with the analgesic effect of acupuncture in patients with chronic pain. Seven patients presenting with a chronic pain syndrome and 5 healthy controls were included. All single-photon emission computed tomography (SPECT) scans were acquired with a uniform protocol. The patient group was injected with the radioisotope hexamethyl propyleneamine oxime (HMPAO) while experiencing their usual level of pain. A baseline scan was acquired approximately 20 minutes after administration of the HMPAO. The patient then underwent acupuncture therapy with needles placed in points specifically selected to relieve pain. When the pain improved, as determined by a 10-digit score for pain assessment, the patient was reinjected with HMPAO and imaged 20 minutes later for the acupuncture scan. The reference group also had a baseline and acupuncture scan, although the acupuncture itself was performed using a standardized set of needle points. The reference group participants were found to have significant increases in the thalamic and prefrontal cortex activity on the acupuncture scan compared to the baseline. The baseline scans of the pain patients showed significant asymmetric uptake in the thalami compared to controls. This asymmetry reversed or normalized after the acupuncture therapy. Significant correlations were observed between the change of activity in the prefrontal cortex and ipsilateral sensorimotor area. The results from these cases show that HMPAO-SPECT is capable of detecting changes in cerebral blood flow associated with pain and that acupuncture analgesia is associated with changes in the activity of the frontal lobes, brain stem, and thalami.

A Single-Photon Emission Computed Tomography Imaging Study of Driving Impairment in Patients with Alzheimer’s Disease

Single-photon emission computed tomography (SPECT) was used in this study to examine the neurophysiologic basis of driving impairment in 79 subjects with dementia. Driving impairment, as measured by caregiver ratings, was significantly related to regional reduction of right hemisphere cortical perfusion on SPECT, particularly in the temporo-occipital area. With increased severity of driving impairment, frontal cortical perfusion was also reduced. Clock drawing was more significantly related to driving impairment than the Mini-Mental State Examination (MMSE). Driving impairment in Alzheimer’s disease is related to changes in cortical function which vary according to the severity of the disease. Cognitive tests of visuoperceptual and executive functions may be more useful screening tools for identifying those at greatest risk for driving problems than examinations like the MMSE that are weighted toward left-hemisphere-based verbal tasks.

The preclinical pharmacologic study of dopamine transporter imaging agent [ 99mTc]TRODAT-1

The purpose of this study was to investigate the pharmacologic characteristics of TRODAT-1 (2β-((N,N′-bis(2-mercaptoethyl)ethylene diamino)methyl), 3β-(4-chlorophenyl)tropane) labeled with [ 99mTc] as an imaging agent for dopamine transporter (DAT). Radiochemical purity of [ 99mTc]TRODAT-1 was over 90%. The partition coefficients in octanol and buffer were 2.12 and 2.19 at pH 7.0 and 7.4, respectively. Animal studies have been performed in rats, rabbits, and normal and hemi-Parkinsonian model monkeys. Biodistribution displayed moderate uptake in rat brain (0.28 %ID/organ at 2 min) and the striatal uptake was 0.193, 0.142, and 0.136 %ID/g at 2, 60, and 120 min, respectively. The ratios of striatal/cerebellar (ST/CB) uptake were 2.4, 4.45, and 2.45 %ID/g at 60, 120, and 240 min, respectively. The major radioactivity was excreted by the hepatobiliary system. Blood clearance kinetics was performed in rabbits, and the initial half-life of 1.18 min and late half-life of 367.8 min were obtained. Brain single photon emission computed tomography imaging studies in normal monkeys showed the ratios of ST/CB uptake were 1.56–2.0 %ID/g and indicated that both uptake and retention in the striatal area were associated with the DAT. The imaging of hemi-Parkinsonian model monkeys also displayed the expected selectivity, the highest uptake being observed in the basal ganglia area of the normal side. Thereby, it is suggested that [ 99mTc]TRODAT-1 is a safe and useful imaging agent for localization of the presynaptic DAT in the brain.