scholarly journals Biological Distribution of Orally Administered [123I]MIBG for Estimating Gastrointestinal Tract Absorption

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 61
Author(s):  
Masato Kobayashi ◽  
Asuka Mizutani ◽  
Yuka Muranaka ◽  
Kodai Nishi ◽  
Hisakazu Komori ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Organic Cation ◽  
Organic Anion ◽  
Photon Emission ◽  
Experimental Colitis ◽  
Organic Cation Transporter ◽  
Spect Imaging ◽  
Whole Body ◽  
Emission Computed Tomography ◽  
Whole Body Imaging

Gastrointestinal tract absorption of cationic anticancer drugs and medicines was estimated using whole-body imaging following oral [123I]MIBG administration. [123I]MIBG was added to cultures of human embryonic kidney (HEK)293 cells expressing human organic anion transporting polypeptide (OATP)2B1, carnitine/organic cation transporter (OCTN)1 and OCTN2, and organic cation transporter (OCT)1, OCT2, and OCT3 with and without cimetidine (an OCTN and OCT inhibitor) and L-carnitine (an OCTN inhibitor). Biodistribution analyses and single-photon emission computed tomography (SPECT) imaging in normal and dextran sodium sulfate (DSS)-induced experimental colitis mice were conducted using [123I]MIBG with and without cimetidine. [123I]MIBG uptake was significantly higher in HEK293/OCTN1, 2, and OCT1-3 cells than in mock cells. Uptake via OCTN was inhibited by L-carnitine, whereas OCT-mediated uptake was inhibited by cimetidine. Biodistribution analyses and SPECT imaging studies showed significantly lower accumulation of [123I]MIBG in the blood, heart, liver, and bladder in DSS-induced experimental colitis mice and mice with cimetidine loading compared with normal mice, whereas significantly higher accumulation in the stomach and kidney was observed after [123I]MIBG injection. [123I]MIBG imaging after oral administration can be used to estimate gastrointestinal absorption in the small intestine via OCTN and/or OCT by measuring radioactivity in the heart, liver, and bladder.

scholarly journals Radionuclide, magnetic resonance and computed tomography imaging in European round back slugs (Arionidae) and leopard slugs (Limacidae)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicola Beindorff ◽  
Fabian Schmitz-Peiffer ◽  
Daniel Messroghli ◽  
Winfried Brenner ◽  
Janet F. Eary
Keyword(s):  
Computed Tomography ◽  
Magnetic Resonance ◽  
Kidney Function ◽  
Single Photon ◽  
Photon Emission ◽  
Functional Anatomy ◽  
Whole Body ◽  
Emission Computed Tomography ◽  
Whole Body Imaging ◽  
Imaging Protocol

AbstractOther than in animal models of human disease, little functional imaging has been performed in most of the animal world. The aim of this study was to explore the functional anatomy of the European round back slug (Arionidae) and leopard slug (Limacidae) and to establish an imaging protocol for comparative species study. Radionuclide images with single photon emission computed tomography (SPECT) and positron emission tomography (PET) were obtained after injections of standard clinical radiopharmaceuticals 99mtechnetium dicarboxypropane diphosphonate (bone scintigraphy), 99mtechnetium mercaptoacetyltriglycine (kidney function), 99mtechnetium diethylenetriaminepentaacetic acid (kidney function), 99mtechnetium pertechnetate (mediated by the sodium-iodide symporter), 99mtechnetium sestamibi (cardiac scintigraphy) or 18F-fluoro-deoxyglucose (glucose metabolism) in combination with magnetic resonance imaging (MRI) and computed tomography (CT) for uptake anatomic definition. Images were compared with anatomic drawings for the Arionidae species. Additionally, organ uptake data was determined for a description of slug functional anatomy in comparison to human tracer biodistribution patterns identifying the heart, the open circulatory anatomy, calcified shell remnant, renal structure (nephridium), liver (digestive gland) and intestine. The results show the detailed functional anatomy of Arionidae and Limacidae, and describe an in vivo whole-body imaging procedure for invertebrate species.

scholarly journals Single photon emission computed tomography (SPECT)/computed tomography using Iodine-123 in patients with differentiated thyroid cancer: additional value over whole body planar imaging and SPECT

2010 ◽  
Vol 162 (6) ◽  
pp. 1131-1139 ◽  
Author(s):  
Tara Barwick ◽  
Iain Murray ◽  
Hakim Megadmi ◽  
William M Drake ◽  
P Nick Plowman ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Thyroid Cancer ◽  
Single Photon ◽  
Photon Emission ◽  
Spect Imaging ◽  
Whole Body ◽  
Emission Computed Tomography ◽  
Iodine 123 ◽  
Single Photon Emission Computed ◽  
Photon Emission Computed Tomography

ObjectiveThe aim of the study was to assess the diagnostic performance of co-registered single photon emission computed tomography (SPECT)/computed tomography (CT) compared to Iodine-123 whole body gamma camera (WBGC) imaging and to SPECT alone in patients with differentiated thyroid cancer.MethodsWBGC and SPECT/CT (n=85) imaging of the neck and thorax was performed in 79 consecutive patients. Three experienced observers reviewed: i) WBGC images followed by ii) SPECT alone, and iii) co-registered SPECT/CT. Foci of increased radioiodine uptake were classified on a five-point scale. Biopsy, other imaging modalities, and clinical follow-up served as the reference standard.ResultsTwenty-two patients had local recurrence or metastatic thyroid cancer (11 were radioiodine negative), 9 had remnant thyroid tissue, and 54 had no evidence of disease. When classifying equivocal, probably, and definitely malignant findings as positive for malignancy, the sensitivity, specificity, positive predictive value, and negative predictive value were as follows: 41, 68, 31, and 77% for WBGC imaging; 45, 89, 59, and 82% for WBGC plus SPECT imaging; and 50, 100, 100, and 85% for WBGC plus SPECT/CT imaging respectively. The specificity was improved by the addition of SPECT (P=0.0002) and SPECT/CT (P<0.0001) than to WBGC imaging. SPECT/CT was also more specific than WBGC plus SPECT imaging (P=0.016). In a study-based analysis, SPECT/CT provided additional diagnostic information in 42% (36/85) of cases. SPECT/CT provided further characterization in 70% (63/90) of foci and improved the diagnostic confidence of all three observers.ConclusionThe addition of SPECT/CT significantly improved the diagnostic information over Iodine-123 WBGC imaging and WBGC plus SPECT imaging alone.

scholarly journals GEP-NETs update: Functional localisation and scintigraphy in neuroendocrine tumours of the gastrointestinal tract and pancreas (GEP-NETs)

2014 ◽  
Vol 170 (5) ◽  
pp. R173-R183 ◽  
Author(s):  
Wouter W de Herder
Keyword(s):  
Gastrointestinal Tract ◽  
Functional Imaging ◽  
Health Care Professionals ◽  
Neuroendocrine Tumours ◽  
Single Photon ◽  
Primary Tumour ◽  
Photon Emission ◽  
Whole Body ◽  
Whole Body Imaging ◽  
Sampling Procedures

For patients with neuroendocrine tumours (NETs) of the gastrointestinal tract and pancreas (GEP) (GEP-NETs), excellent care should ideally be provided by a multidisciplinary team of skilled health care professionals. In these patients, a combination of nuclear medicine imaging and conventional radiological imaging techniques is usually mandatory for primary tumour visualisation, tumour staging and evaluation of treatment. In specific cases, as in patients with occult insulinomas, sampling procedures can provide a clue as to where to localise the insulin-hypersecreting pancreatic NETs. Recent developments in these fields have led to an increase in the detection rate of primary GEP-NETs and their metastatic deposits. Radiopharmaceuticals targeted at specific tumour cell properties and processes can be used to provide sensitive and specific whole-body imaging. Functional imaging also allows for patient selection for receptor-based therapies and prediction of the efficacy of such therapies. Positron emission tomography/computed tomography (CT) and single-photon emission CT/CT are used to map functional images with anatomical localisations. As a result, tumour imaging and tumour follow-up strategies can be optimised for every individual GEP-NET patient. In some cases, functional imaging might give indications with regard to future tumour behaviour and prognosis.

scholarly journals Inhibition of the Hepatic Uptake of 99mTc-Tetrofosmin Using an Organic Cation Transporter Blocker

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1073
Author(s):  
Kodai Nishi ◽  
Masato Kobayashi ◽  
Minori Kikuchi ◽  
Asuka Mizutani ◽  
Yuka Muranaka ◽  
...  
Keyword(s):  
Organic Cation ◽  
Organic Anion ◽  
Specific Inhibitor ◽  
In Vitro Study ◽  
Organic Cation Transporter ◽  
Vitro Study ◽  
Hek293 Cells ◽  
Emission Computed Tomography ◽  
99Mtc Tetrofosmin

The accumulation of high levels of 99mTc-tetrofosmin (99mTc-TF) in the hepatobiliary system can lead to imaging artifacts and interference with diagnosis. The present study investigated the transport mechanisms of 99mTc-TF and attempted to apply competitive inhibition using a specific inhibitor to reduce 99mTc-TF hepatic accumulation. In this in vitro study, 99mTc-TF was incubated in HEK293 cells expressing human organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, OATP2B1, organic anion transporter 2 (OAT2), organic cation transporter 1 (OCT1), OCT2, and Na+-taurocholate cotransporting polypeptide with or without each specific inhibitor to evaluate the contribution of each transporter to 99mTc-TF transportation. In vivo studies, dynamic planar imaging, and single photon emission computed tomography (SPECT) experiments with rats were performed to observe alterations to 99mTc-TF pharmacokinetics using cimetidine (CMT) as an OCT1 inhibitor. Time–activity curves in the liver and heart were acquired from dynamic data, and the 99mTc-TF uptake ratio was calculated from SPECT. From the in vitro study, 99mTc-TF was found to be transported by OCT1 and OCT2. When CMT-preloaded rats and control rats were compared, the hepatic accumulation of the 99mTc-TF was reduced, and the time to peak heart count shifted to an earlier stage. The hepatic accumulation of 99mTc-TF was markedly suppressed, and the heart-to-liver ratio increased 1.6-fold. The pharmacokinetics of 99mTc-TF were greatly changed by OCT1 inhibitor. Even in humans, the administration of OCT1 inhibitor before cardiac SPECT examination may reduce 99mTc-TF hepatic accumulation and contribute to the suppression of artifacts and the improvement of SPECT image quality.

scholarly journals Correlation of an Index-Lesion-Based SPECT Dosimetry Method with Mean Tumor Dose and Clinical Outcome after 177Lu-PSMA-617 Radioligand Therapy

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 428
Author(s):  
Friederike Völter ◽  
Lena Mittlmeier ◽  
Astrid Gosewisch ◽  
Julia Brosch-Lenz ◽  
Franz Josef Gildehaus ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Single Photon ◽  
Photon Emission ◽  
Whole Body ◽  
Biochemical Response ◽  
Emission Computed Tomography ◽  
Radioligand Therapy ◽  
Index Lesion ◽  
Recist 1.1 ◽  
Psma Pet

Background: Dosimetry can tailor prostate-specific membrane-antigen-targeted radioligand therapy (PSMA-RLT) for metastatic castration-resistant prostate cancer (mCRPC). However, whole-body tumor dosimetry is challenging in patients with a high tumor burden. We evaluate a simplified index-lesion-based single-photon emission computed tomography (SPECT) dosimetry method in correlation with clinical outcome. Methods: 30 mCRPC patients were included (median 71 years). The dosimetry was performed for the first cycle using quantitative 177Lu-SPECT. The response was evaluated using RECIST 1.1 and PERCIST criteria, as well as changes in PSMA-positive tumor volume (PSMA-TV) in post-therapy PSMA-PET and biochemical response according to PSA changes after two RLT cycles. Results: Mean tumor doses as well as index-lesion doses were significantly higher in PERCIST responders compared to non-responders (10.2 ± 12.0 Gy/GBq vs. 4.0 ± 2.9 Gy/GBq, p = 0.03 and 13.7 ± 14.2 Gy/GBq vs. 5.9 ± 4.4 Gy/GBq, p = 0.04, respectively). No significant differences in mean tumor and index lesion doses were observed between responders and non-responders according to RECIST 1.1, PSMA-TV, and biochemical response criteria. Conclusion: Compared to mean tumor doses on a patient level, single index-lesion-based SPECT dosimetry correlates equally well with the response to PSMA-RLT according to PERCIST criteria and may represent a fast and feasible dosimetry approach for clinical routine.

scholarly journals PET and SPECT Imaging of the EGFR Family (RTK Class I) in Oncology

2021 ◽  
Vol 22 (7) ◽  
pp. 3663
Author(s):  
Sara S. Rinne ◽  
Anna Orlova ◽  
Vladimir Tolmachev
Keyword(s):  
Single Photon ◽  
Photon Emission ◽  
Growth Factor Receptor ◽  
Spect Imaging ◽  
Emission Tomography ◽  
Class I ◽  
Whole Body ◽  
Her Family ◽  
Endogenous Expression ◽  
Egfr Family

The human epidermal growth factor receptor family (EGFR-family, other designations: HER family, RTK Class I) is strongly linked to oncogenic transformation. Its members are frequently overexpressed in cancer and have become attractive targets for cancer therapy. To ensure effective patient care, potential responders to HER-targeted therapy need to be identified. Radionuclide molecular imaging can be a key asset for the detection of overexpression of EGFR-family members. It meets the need for repeatable whole-body assessment of the molecular disease profile, solving problems of heterogeneity and expression alterations over time. Tracer development is a multifactorial process. The optimal tracer design depends on the application and the particular challenges of the molecular target (target expression in tumors, endogenous expression in healthy tissue, accessibility). We have herein summarized the recent preclinical and clinical data on agents for Positron Emission Tomography (PET) and Single Photon Emission Tomography (SPECT) imaging of EGFR-family receptors in oncology. Antibody-based tracers are still extensively investigated. However, their dominance starts to be challenged by a number of tracers based on different classes of targeting proteins. Among these, engineered scaffold proteins (ESP) and single domain antibodies (sdAb) show highly encouraging results in clinical studies marking a noticeable trend towards the use of smaller sized agents for HER imaging.

SPECT Scan in Somatization Disorder Patients: An Exploratory Study of Eleven Cases

2001 ◽  
Vol 35 (3) ◽  
pp. 359-363 ◽  
Author(s):  
Javier Garcia-Campayo ◽  
Concepcion Sanz-Carrillo ◽  
Teresa Baringo ◽  
Concepción Ceballos
Keyword(s):  
Computed Tomography ◽  
Single Photon ◽  
Photon Emission ◽  
Spect Imaging ◽  
The Other ◽  
University Hospital ◽  
Somatization Disorder ◽  
Emission Computed Tomography ◽  
Axis I ◽  
Pain Symptoms

Objective: There are no previous studies using single photon emission computed tomography (SPECT) scans in somatization disorder (SD) patients. The aim of this paper is to assess SPECT imaging abnormalities in SD patients and study any relation to laterality. Method: Eleven SD patients from the Somatization Disorder Unit of Miguel Servet University Hospital, Zaragoza, Spain, not fulfilling criteria for any other psychiatric disorder and showing normal computed tomography (CT) and magnetic resonance imaging (MRI) images were studied with SPECT. Patients with DSM-IV axis I comorbidity were ruled out because it has been demonstrated that SPECT scans can show abnormalities in patients with depression and anxiety disorders. The technique used for SPECT was 99mTc-D,1,hexamethylpropyleneamide- oxime (99mTc-HMPAO) in four patients and 99mTc-bicisate in the other seven. The SPECT scans were evaluated without knowledge of clinical data and entirely by visual inspection. Results: Seven out of 11 (63.6%) SD patients showed hypoperfusion in SPECT imaging. In four cases there was hypoperfusion in the non-dominant hemisphere and the predominance of pain symptoms took place in the contralateral hemibody. In the other three patients hypoperfusion was bilateral. The anatomical regions affected were cerebellum (four cases), frontal and prefrontal areas (three cases), temporoparietal areas (two cases) and the complete hemisphere (one case). Conclusions: A proportion of SD patients may present hypoperfusion in SPECT images, uni- or bilaterally, in different brain areas. Possible aetiological explanations for this finding are discussed. Controlled studies are necessary to confirm or refute this hypothesis.

scholarly journals Renal secretion of hydrochlorothiazide involves organic anion transporter 1/3, organic cation transporter 2, and multidrug and toxin extrusion protein 2-K

2019 ◽  
Vol 317 (4) ◽  
pp. F805-F814
Author(s):  
Jia Yin ◽  
David J. Wagner ◽  
Bhagwat Prasad ◽  
Nina Isoherranen ◽  
Kenneth E. Thummel ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Organic Cation ◽  
Organic Anion ◽  
Organic Cation Transporter ◽  
Tubular Secretion ◽  
Organic Anion Transporter ◽  
Anion Transporters ◽  
Anion Transporter ◽  
Organic Cation Transporter 2 ◽  
Toxin Extrusion

Hydrochlorothiazide (HCTZ) is the most widely used thiazide diuretic for the treatment of hypertension either alone or in combination with other antihypertensives. HCTZ is mainly cleared by the kidney via tubular secretion, but the underlying molecular mechanisms are unclear. Using cells stably expressing major renal organic anion and cation transporters [human organic anion transporter 1 (hOAT1), human organic anion transporter 3 (hOAT3), human organic cation transporter 2 (hOCT2), human multidrug and toxin extrusion 1 (hMATE1), and human multidrug and toxin extrusion 2-K (hMATE2-K)], we found that HCTZ interacted with both organic cation and anion transporters. Uptake experiments further showed that HCTZ is transported by hOAT1, hOAT3, hOCT2, and hMATE2-K but not by hMATE1. Detailed kinetic analysis coupled with quantification of membrane transporter proteins by targeted proteomics revealed that HCTZ is an excellent substrate for hOAT1 and hOAT3. The apparent affinities ( Km) for hOAT1 and hOAT3 were 112 ± 8 and 134 ± 13 μM, respectively, and the calculated turnover numbers ( kcat) were 2.48 and 0.79 s−1, respectively. On the other hand, hOCT2 and hMATE2-K showed much lower affinity for HCTZ. The calculated transport efficiency ( kcat/ Km) at the single transporter level followed the rank order of hOAT1> hOAT3 > hOCT2 and hMATE2-K, suggesting a major role of organic anion transporters in tubular secretion of HCTZ. In vitro inhibition experiments further suggested that HCTZ is not a clinically relevant inhibitor for hOAT1 or hOAT3. However, strong in vivo inhibitors of hOAT1/3 may alter renal secretion of HCTZ. Together, our study elucidated the molecular mechanisms underlying renal handling of HCTZ and revealed potential pathways involved in the disposition and drug-drug interactions for this important antihypertensive drug in the kidney.

Functional Neuroimaging: A Transformative Tool for Integrative Psychiatry

2018 ◽  
Author(s):  
Abass Alavi ◽  
Andrew B. Newberg
Keyword(s):  
Psychiatric Disorders ◽  
Functional Neuroimaging ◽  
Single Photon ◽  
Cerebral Metabolism ◽  
Photon Emission ◽  
Spect Imaging ◽  
Emission Computed Tomography ◽  
Positron Emission ◽  
Integrative Psychiatry ◽  
Integrative Therapies

Functional neuroimaging with positron emission tomography (PET), single photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI) can be highly useful in the evaluation and management of patients with psychiatric disorders. PET and SPECT imaging typically evaluate cerebral metabolism and blood flow, respectively, and can determine patterns associated with different disorders such as depression or schizophrenia. PET and SPECT imaging can also evaluate neurotransmitter changes such as dopamine or serotonin associated with different psychiatric disorders. fMRI is an excellent tool for studying the effects of psychiatric disorders on specific brain processes related to cognition and mood. fMRI activations studies allow researchers to present various stimuli to a subject in order to determine how the brain reacts and whether psychiatric disorders are associated with different brain reactivity patterns. Functional neuroimaging with PET, SPECT, and fMRI can be highly useful in the investigation of the mechanism of action of integrative therapies for psychiatric disorders.

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