scholarly journals Quantitative Accuracy of Low-Count SPECT Imaging in Phantom and In Vivo Mouse Studies

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Ciara M. Finucane ◽  
Iain Murray ◽  
Jane K. Sosabowski ◽  
Julie M. Foster ◽  
Stephen J. Mather

We investigated the accuracy of a single photon emission computed tomography (SPECT) system in quantifying a wide range of radioactivity concentrations using different scan times in both phantom and animal models. A phantom containing various amounts of In-111 or Tc-99m was imaged until the activity had decayed close to background levels. Scans were acquired for different durations, employing different collimator pinhole sizes. VOI analysis was performed to quantify uptake in the images and the values compared to the true activity. The phantom results were then validated in tumour-bearing mice. The use of an appropriate calibration phantom and disabling of a background subtraction feature meant that absolute errors were within 12% of the true activity. Furthermore, a comparison of in vivo imaging and biodistribution studies in mice showed a correlation of 0.99 for activities over the 200 kBq to 5 MBq range. We conclude that the quantitative information provided by the NanoSPECT camera is accurate and allows replacement of dissection studies for assessment of radiotracer biodistribution in mouse models.

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 237 ◽  
Author(s):  
Ana Castro-Balado ◽  
Cristina Mondelo-García ◽  
Miguel González-Barcia ◽  
Irene Zarra-Ferro ◽  
Francisco J Otero-Espinar ◽  
...  

Classical methodologies used in ocular pharmacokinetics studies have difficulties to obtain information about topical and intraocular distribution and clearance of drugs and formulations. This is associated with multiple factors related to ophthalmic physiology, as well as the complexity and invasiveness intrinsic to the sampling. Molecular imaging is a new diagnostic discipline for in vivo imaging, which is emerging and spreading rapidly. Recent developments in molecular imaging techniques, such as positron emission tomography (PET), single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI), allow obtaining reliable pharmacokinetic data, which can be translated into improving the permanence of the ophthalmic drugs in its action site, leading to dosage optimisation. They can be used to study either topical or intraocular administration. With these techniques it is possible to obtain real-time visualisation, localisation, characterisation and quantification of the compounds after their administration, all in a reliable, safe and non-invasive way. None of these novel techniques presents simultaneously high sensitivity and specificity, but it is possible to study biological procedures with the information provided when the techniques are combined. With the results obtained, it is possible to assume that molecular imaging techniques are postulated as a resource with great potential for the research and development of new drugs and ophthalmic delivery systems.


2003 ◽  
Vol 42 (04) ◽  
pp. 173-180 ◽  
Author(s):  
M. P. Law ◽  
K. Kopka ◽  
St. Wagner ◽  
S. Luthra ◽  
V. W. Pike ◽  
...  

Summary: Aim: As results of cardiac biopsies suggest, myocardial β1-adrenoceptor density is reduced in patients with chronic heart failure. However, changes in cardiac β2-adrenoceptors vary. With suitable radiopharmaceuticals single photon emission computed tomography (SPECT) and positron emission tomography (PET) offer the opportunity to assess β-adrenoceptors non-invasively. Among the novel racemic analogues of the established β1-selective adrenoceptor antagonist ICI 89.406 the iodinated 2-I-ICI-H showed high affinity and selectivity to β1-adrenoceptors in murine ventricular membranes. The aim of this study was its evaluation as a putative sub-type selective β1-adrenergic radioligand in cardiac imaging. Methods: Competition studies in vitro and in vivo were used to investigate the kinetics of 2-I-ICI-H binding to cardiac β-adrenoceptors in mice and rats. In addition, the radiosynthesis of 2-125I-ICI-H from the silylated precursor 2-SiMe3-ICI-H was established. The specific activity was 80 GBq/µmol, the radiochemical yield ranged from 70 to 80%. Results: The unlabelled compound 2-I-ICI-H showed high β1-selectivity and -affinity in the in vitro competition studies. In vivo biodistribution studies apparently showed low affinity to cardiac β-adrenoceptors. The radiolabelled counterpart 2-125I-ICI-H showed a high degree of non-specific binding in vitro and no specific binding to cardiac β1-adrenoceptors in vivo. Conclusion: Because of its high non-specific binding 2-125I-ICI-H is no suitable radiotracer for imaging in vivo.


2020 ◽  
Vol 13 (10) ◽  
pp. 272
Author(s):  
Falco Reissig ◽  
David Bauer ◽  
Martin Ullrich ◽  
Martin Kreller ◽  
Jens Pietzsch ◽  
...  

Barium-131 is a single photon emission computed tomography (SPECT)-compatible radionuclide for nuclear medicine and a promising diagnostic match for radium-223/-224. Herein, we report on the sufficient production route 133Cs(p,3n)131Ba by using 27.5 MeV proton beams. An average of 190 MBq barium-131 per irradiation was obtained. The SR Resin-based purification process led to barium-131 in high radiochemical purity. An isotopic impurity of 0.01% barium-133 was detectable. For the first time, radiolabeling of the ligand macropa with barium-131 was performed. Radiolabeling methods under mild conditions and reaction controls based on TLC systems were successfully applied. Small animal SPECT/ computed tomography (CT) measurements and biodistribution studies were performed using [131Ba]Ba(NO3)2 as reference and 131Ba-labeled macropa in healthy mice for the first time. Biodistribution studies revealed the expected rapid bone uptake of [131Ba]Ba2+, whereas 131Ba-labeled macropa showed a fast clearance from the blood, thereby showing a significantly (p < 0.001) lower accumulation in the bone. We conclude that barium-131 is a promising SPECT radionuclide and delivers appropriate imaging qualities in small animals. Furthermore, the relative stability of the 131Ba-labeled macropa complex in vivo forms the basis for the development of sufficient new chelators, especially for radium isotopes. Thereby, barium-131 will attain its goal as a diagnostic match to the alpha emitters radium-223 and radium-224.


2016 ◽  
Vol 94 (9) ◽  
pp. 773-780 ◽  
Author(s):  
Stephanie M. Rathmann ◽  
Nancy Janzen ◽  
John F. Valliant

Molecular probes that target specific markers expressed in solid tumours are in demand for cancer imaging and radionuclide therapy applications. The synthesis, characterization, and in vivo evaluation of radioiodinated triazoles designed as probes to target melanoma are described here. Compounds were prepared using a thermal click reaction between ethynylstannane and methyl 2-azidoacetate, resulting in preferential formation of the corresponding 1,4-tin triazole. The primary amine of various targeting vectors was then coupled to the resulting tin triazole methyl ester. These precursors were labelled with no carrier added 123I or 125I and purified by high performance liquid chromatography to give isolated radiochemical yields between 6% and 51% and radiochemical purities of >95% in all cases. Among the evaluated compounds, N-(2-diethylamino-ethyl)-2-(4-iodo-[1,2,3]triazol-1-yl)acetamide (7a) and N-(1-benzylpiperidin-4-yl)-2-(4-iodo-1H-1,2,3-triazol-1-yl)acetamide (7d) showed the most promising in vivo data, and their 123I-labelled forms were used in single photon emission computed tomography computed tomography (SPECT–CT) imaging studies. The imaging data showed excellent tumour visualization with a very high signal to noise ratio.


2019 ◽  
Vol 19 (12) ◽  
pp. 950-960
Author(s):  
Soghra Farzipour ◽  
Seyed Jalal Hosseinimehr

Tumor-targeting peptides have been generally developed for the overexpression of tumor specific receptors in cancer cells. The use of specific radiolabeled peptide allows tumor visualization by single photon emission computed tomography (SPECT) and positron emission tomography (PET) tools. The high affinity and specific binding of radiolabeled peptide are focusing on tumoral receptors. The character of the peptide itself, in particular, its complex molecular structure and behaviors influence on its specific interaction with receptors which are overexpressed in tumor. This review summarizes various strategies which are applied for the expansion of radiolabeled peptides for tumor targeting based on in vitro and in vivo specific tumor data and then their data were compared to find any correlation between these experiments. With a careful look at previous studies, it can be found that in vitro unblock-block ratio was unable to correlate the tumor to muscle ratio and the success of radiolabeled peptide for in vivo tumor targeting. The introduction of modifiers’ approaches, nature of peptides, and type of chelators and co-ligands have mixed effect on the in vitro and in vivo specificity of radiolabeled peptides.


Author(s):  
Lidia Bellés ◽  
Andrea Dimiziani ◽  
Stergios Tsartsalis ◽  
Philippe Millet ◽  
François R Herrmann ◽  
...  

Abstract Background Impulsivity and novelty preference are both associated with an increased propensity to develop addiction-like behaviors, but their relationship and respective underlying dopamine (DA) underpinnings are not fully elucidated. Methods We evaluated a large cohort (n = 49) of Roman high- and low-avoidance rats using single photon emission computed tomography to concurrently measure in vivo striatal D2/3 receptor (D2/3R) availability and amphetamine (AMPH)-induced DA release in relation to impulsivity and novelty preference using a within-subject design. To further examine the DA-dependent processes related to these traits, midbrain D2/3-autoreceptor levels were measured using ex vivo autoradiography in the same animals. Results We replicated a robust inverse relationship between impulsivity, as measured with the 5-choice serial reaction time task, and D2/3R availability in ventral striatum and extended this relationship to D2/3R levels measured in dorsal striatum. Novelty preference was positively related to impulsivity and showed inverse associations with D2/3R availability in dorsal striatum and ventral striatum. A high magnitude of AMPH-induced DA release in striatum predicted both impulsivity and novelty preference, perhaps owing to the diminished midbrain D2/3-autoreceptor availability measured in high-impulsive/novelty-preferring Roman high-avoidance animals that may amplify AMPH effect on DA transmission. Mediation analyses revealed that while D2/3R availability and AMPH-induced DA release in striatum are both significant predictors of impulsivity, the effect of striatal D2/3R availability on novelty preference is fully mediated by evoked striatal DA release. Conclusions Impulsivity and novelty preference are related but mediated by overlapping, yet dissociable, DA-dependent mechanisms in striatum that may interact to promote the emergence of an addiction-prone phenotype.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 770
Author(s):  
Patrick M. Perrigue ◽  
Richard A. Murray ◽  
Angelika Mielcarek ◽  
Agata Henschke ◽  
Sergio E. Moya

Nanoformulations offer multiple advantages over conventional drug delivery, enhancing solubility, biocompatibility, and bioavailability of drugs. Nanocarriers can be engineered with targeting ligands for reaching specific tissue or cells, thus reducing the side effects of payloads. Following systemic delivery, nanocarriers must deliver encapsulated drugs, usually through nanocarrier degradation. A premature degradation, or the loss of the nanocarrier coating, may prevent the drug’s delivery to the targeted tissue. Despite their importance, stability and degradation of nanocarriers in biological environments are largely not studied in the literature. Here we review techniques for tracing the fate of nanocarriers, focusing on nanocarrier degradation and drug release both intracellularly and in vivo. Intracellularly, we will discuss different fluorescence techniques: confocal laser scanning microscopy, fluorescence correlation spectroscopy, lifetime imaging, flow cytometry, etc. We also consider confocal Raman microscopy as a label-free technique to trace colocalization of nanocarriers and drugs. In vivo we will consider fluorescence and nuclear imaging for tracing nanocarriers. Positron emission tomography and single-photon emission computed tomography are used for a quantitative assessment of nanocarrier and payload biodistribution. Strategies for dual radiolabelling of the nanocarriers and the payload for tracing carrier degradation, as well as the efficacy of the payload delivery in vivo, are also discussed.


2018 ◽  
Vol 78 (2) ◽  
pp. 218-227 ◽  
Author(s):  
Janine Schniering ◽  
Martina Benešová ◽  
Matthias Brunner ◽  
Stephanie Haller ◽  
Susan Cohrs ◽  
...  

ObjectiveTo evaluate integrin αvβ3 (alpha-v-beta-3)-targeted and somatostatin receptor 2 (SSTR2)-targeted nuclear imaging for the visualisation of interstitial lung disease (ILD).MethodsThe pulmonary expression of integrin αvβ3 and SSTR2 was analysed in patients with different forms of ILD as well as in bleomycin (BLM)-treated mice and respective controls using immunohistochemistry. Single photon emission CT/CT (SPECT/CT) was performed on days 3, 7 and 14 after BLM instillation using the integrin αvβ3-targeting 177Lu-DOTA-RGD and the SSTR2-targeting 177Lu-DOTA-NOC radiotracer. The specific pulmonary accumulation of the radiotracers over time was assessed by in vivo and ex vivo SPECT/CT scans and by biodistribution studies.ResultsExpression of integrin αvβ3 and SSTR2 was substantially increased in human ILD regardless of the subtype. Similarly, in lungs of BLM-challenged mice, but not of controls, both imaging targets were stage-specifically overexpressed. While integrin αvβ3 was most abundantly upregulated on day 7, the inflammatory stage of BLM-induced lung fibrosis, SSTR2 expression peaked on day 14, the established fibrotic stage. In agreement with the findings on tissue level, targeted nuclear imaging using SPECT/CT specifically detected both imaging targets ex vivo and in vivo, and thus visualised different stages of experimental ILD.ConclusionOur preclinical proof-of-concept study suggests that specific visualisation of molecular processes in ILD by targeted nuclear imaging is feasible. If transferred into clinics, where imaging is considered an integral part of patients’ management, the additional information derived from specific imaging tools could represent a first step towards precision medicine in ILD.


Diagnostics ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 145
Author(s):  
Sergey Gavrilov ◽  
Anatoly Karalkin ◽  
Nadezhda Mishakina ◽  
Oksana Efremova ◽  
Anastasia Grishenkova

The causes of chronic pelvic pain (CPP) in patients with pelvic venous disorder (PeVD) are not completely understood. Various authors consider dilation of pelvic veins (PeVs) and pelvic venous reflux (PVR) as the main mechanisms underlying symptomatic forms of PeVD. The aim of this study was to assess relationships of pelvic vein dilation and PVR with clinical manifestations of PeVD. This non-randomized comparative cohort study included 80 female patients with PeVD who were allocated into two groups with symptomatic (n = 42) and asymptomatic (n = 38) forms of the disease. All patients underwent duplex scanning and single-photon emission computed tomography (SPECT) of PeVs with in vivo labeled red blood cells (RBCs). The PeV diameters, the presence, duration and pattern of PVR in the pelvic veins, as well as the coefficient of pelvic venous congestion (CPVC) were assessed. Two groups did not differ significantly in pelvic vein diameters (gonadal veins (GVs): 7.7 ± 1.3 vs. 8.5 ± 0.5 mm; parametrial veins (PVs): 9.8 ± 0.9 vs. 9.5 ± 0.9 mm; and uterine veins (UVs): 5.6 ± 0.2 vs. 5.5 ± 0.6 mm). Despite this, CPVC was significantly higher in symptomatic versus asymptomatic patients (1.9 ± 0.4 vs. 0.7 ± 0.2, respectively; p = 0.008). Symptomatic patients had type II or III PVR, while asymptomatic patients had type I PVR. The reflux duration was found to be significantly greater in symptomatic versus asymptomatic patients (median and interquartile range: 4.0 [3.0; 5.0] vs. 1.0 [0; 2.0] s for GVs, p = 0.008; 4.0 [3.0; 5.0] vs. 1.1 [1.0; 2.0] s for PVs, p = 0.007; and 2.0 [2.0; 3.0] vs. 1.0 [1.0; 2.0] s for UVs, p = 0.04). Linear correlation analysis revealed a strong positive relationship (Pearson’s r = 0.78; p = 0.007) of CPP with the PVR duration but not with vein diameter. The grade of PeV dilation may not be a determining factor in CPP development in patients with PeVD. The presence and duration of reflux in the pelvic veins were found to be predictors of the development of symptomatic PeVD.


2002 ◽  
Vol 22 (9) ◽  
pp. 1035-1041 ◽  
Author(s):  
Brian J. Bacskai ◽  
William E. Klunk ◽  
Chester A. Mathis ◽  
Bradley T. Hyman

Alzheimer disease (AD) is an illness that can only be diagnosed with certainty with postmortem examination of brain tissue. Tissue samples from afflicted patients show neuronal loss, neurofibrillary tangles (NFTs), and amyloid-β plaques. An imaging technique that permitted in vivo detection of NFTs or amyloid-β plaques would be extremely valuable. For example, chronic imaging of senile plaques would provide a readout of the efficacy of experimental therapeutics aimed at removing these neuropathologic lesions. This review discusses the available techniques for imaging amyloid-β deposits in the intact brain, including magnetic resonance imaging, positron emission tomography, single photon emission computed tomography, and multiphoton microscopy. A variety of agents that target amyloid-β deposits specifically have been developed using one or several of these imaging modalities. The difficulty in developing these tools lies in the need for the agents to cross the blood-brain barrier while recognizing amyloid-β with high sensitivity and specificity. This review describes the progress in developing reagents suitable for in vivo imaging of senile plaques.


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