Kinetics, Redistribution And Fate Of Indium-111-Labelled-Platelets In Patients With Aortic Aneurysms

1981 ◽  
Author(s):  
A duP Heyns ◽  
M G Lötter ◽  
P N Badenhorst ◽  
F de Kock ◽  
H Pieters ◽  
...  
Keyword(s):  
Imaging System ◽  
Reticuloendothelial System ◽  
Aortic Aneurysms ◽  
Whole Body ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Normal Limits ◽  
Geometrical Mean ◽  
Indium 111

Platelets of 7 patients with abdominal aortic aneurysms were labelled with In-lll-oxine prior to surgery. The platelets were reinjected with the patient positioned under a scintillation camera with a computer assisted imaging system. Images were acquisitioned daily, areas of interest selected with the computer, organ radioactivity- quantitated with a geometrical mean method and expressed as a percentage of whole body radioactivity. Platelet survival (PS) in the circulation was determined, and disappearance curves fitted to a gamma function “multiple hit” model.Mean PS was shorthened to 143,2 ± 47h (normal 232<17); the dissappearance curves were exponential in all but the two patients who had PS within normal limits. The surgically removed aneurysms were dissected and radioactivity of different layers measured. In-111-activity was confined to the superficial layers of the aneurysm.These techniques allow quantitative studies of the in vivo distribution of labelled platelets. Platelets are deposited in the aneurysms, this shortens PS, the disappearance curves become exponential, and the major sites of deposition of In-111-activity are in the liver and spleen. This indicates that although platelets are damaged and deposited in the aneurysm, the reticuloendothelial system remains a major site of platelet sequestration.

Kinetics And Sites Of Destruction Of Indium-111-Oxine Labelled Platelets In Immune Thrombocytopenic Purpura

1981 ◽  
Author(s):  
A duP Heyns ◽  
P N Badenhorst ◽  
M G Lötter ◽  
F de Kock ◽  
C Herbst ◽  
...  
Keyword(s):  
Imaging System ◽  
Kinetic Studies ◽  
Reticuloendothelial System ◽  
Whole Body ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Thrombocytopenic Purpura ◽  
Indium 111 ◽  
System Acquisition ◽  
In Parenthesis

Kinetics and quantification of the sites of destruction of In-111-oxine labelled autologous platelets was investigated in eight patients with idiopathic thrombocytopenic purpura. The mean platelet count was 17 9 × 109/l; platelets were separated by differential centrifugation and labelled with 5,6 ±2,5 MBq In-111. Whole body and organ In-111-platelet distribution was quantitated with a scintillation camera and a computer assisted imaging system acquisition matrix. Areas of interest were selected with the computer and organ In-111-radioactivity expressed as a percentage of whole body activity. Mean platelet survival was 49,5+29,6h, and the survival curves exponential. Equilibrium percentage organ In-111-radioactivity was (normal values in parenthesis): spleen 33,7±8,8 (31,1 ± 10,2); liver 16,1 ± 9,5 (13,1 ± 1,3); thorax 22,8 ± 3,7 (28,8 ± 5,6). Percentage organ In-111-activity at the time when labelled platelets had been removed from the circulation was: spleen 44,5 ± 16,4 (40 ± 16); liver 16,0 ± 11,5 (32,4 ± 7,2); thorax 19,7±6,0 (17,7 ± 10,3). Thorax activity corresponds to radioactivity in the bony cage of the thorax. Three patterns of platelet sequestration were evident. Three patients had mainly splenic sequestration; two, mainly hepatic sequestration; and three, diffuse reticuloendothelial system sequestration with a major component of platelets destroyed in the bone marrow. Splenectomy was performed in two patients. The pattern of In-111-platelet sequestration was not predictive of response to glucocorticoid therapy or indicative of the necessity for splenectomy. Quantitative In-111-labelled autologous platelet kinetic studies provide a new tool for the investigation of platelet disorders.

scholarly journals Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr- labeled platelets differ

Blood ◽  
1986 ◽  
Vol 67 (1) ◽  
pp. 86-92 ◽  
Author(s):  
P Heyns A du ◽  
PN Badenhorst ◽  
MG Lotter ◽  
H Pieters ◽  
P Wessels ◽  
...  
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Severe Disease ◽  
Reticuloendothelial System ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Antiplatelet Antibody ◽  
Thrombocytopenic Purpura ◽  
Computer Assisted Image ◽  
The Difference

Abstract Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr- labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP.

Kinetics and in Vivo Redistribution of 111Indium-Labelled Human Platelets after Intravenous Protamine Sulphate

1980 ◽  
Vol 44 (02) ◽  
pp. 065-068 ◽  
Author(s):  
A duP Heyns ◽  
M G Lötter ◽  
P N Badenhorst ◽  
H Kotze ◽  
F C Killian ◽  
...  
Keyword(s):  
Imaging System ◽  
Human Platelets ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Protamine Sulphate ◽  
Normal Volunteers ◽  
Activated Platelets ◽  
Platelet Survival ◽  
Platelet Aggregates

SummaryThe pathogenesis of thrombocytopenia induced by intravenous protamine sulphate was studied in six patients who underwent cardiopulmonary bypass surgery, and in three normal volunteers. Autologous platelets were labelled with 111Indium-oxine. Platelet lifespan was determined. In vivo 111In-platelet localization, organ redistribution and sites of destruction were quantitated with a scintillation camera and a computer-assisted imaging system. Protamine induced a transient thrombocytopenia, maximal 5-10 min after injection, and 30-40 min in duration. The thrombocytopenia was accompanied by a transient accumulation of platelets in the liver. The splenic platelet pool remained unaltered and no platelets accumulated in the lungs. Platelet survival, measured in two volunteers, was slightly longer than normal and fitted a linear function best. There was a severe transient neutropenia during the period of thrombocytopenia. We conclude that protamineinduced thrombocytopenia is caused by hepatic accumulation of "activated" platelets or platelet aggregates, the process is reversible, and in the two normal volunteers studied, platelet survival was not affected.

THE EFFECT OF INTRAVENOUS IMMUNOGLOBULIN ON PLATELET KINETICS IN CHRONIC IMMUNE THROMBOCYTOPAENIC PURPURA (ITP)

1987 ◽  
Author(s):  
P N Badenhorst ◽  
H F Kotze ◽  
A duP Heyns ◽  
M G Lotter ◽  
P Wessels ◽  
...  
Keyword(s):  
Intravenous Immunoglobulin ◽  
Kinetic Studies ◽  
Ivig Therapy ◽  
Reticuloendothelial System ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Significant Difference ◽  
Before And After ◽  
High Doses

Most patients with ITP respond to high doses of intravenous immunoglobulin (IVIg) with a transient increase in platelet count. The effect of IVIg on platelet kinetics was studied in 5 patients with chronic ITP. Autologous platelets were labelled with In-111 and mean platelet lifespan (MPLS) calculated; in vivo distribution and sites of platelet sequestration were determined with a scintillation camera and computer assisted image analysis. The studies were performed before and after treatment with 2 g/kg Sandoglobulin. Two groups of patients were identified: those with a splenic platelet sequestration pattern (spleen-liver In-111-activity ratio >1.4) and those with diffuse sequestration of platelets in the reticuloendothelial system (RES).There was a significant difference in mean platelet counts before and after treatment (p<0.05). Patients with a splenic sequestration pattern responded better to IVIg: the MPLS lengthened and the high spleen-liver ratio decreased. In the diffuse RES sequestration pattern group, IVIg had almost no effect on platelet kinetics. We conclude that platelet kinetic studies identify a subgroup of patients with ITP who will respond to IVIg therapy.

scholarly journals Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr- labeled platelets differ

Blood ◽  
1986 ◽  
Vol 67 (1) ◽  
pp. 86-92
Author(s):  
P Heyns A du ◽  
PN Badenhorst ◽  
MG Lotter ◽  
H Pieters ◽  
P Wessels ◽  
...  
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Severe Disease ◽  
Reticuloendothelial System ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Antiplatelet Antibody ◽  
Thrombocytopenic Purpura ◽  
Computer Assisted Image ◽  
The Difference

Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr- labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP.

In Vivo Thromboscintigraphy With Indium-111-Labeled Platelets In A Dog-Catheter Model

1981 ◽  
Author(s):  
D C Price ◽  
M J Lipton ◽  
J A Hartmeyer ◽  
R J Prager
Keyword(s):  
Carotid Artery ◽  
Computer Processing ◽  
Catheter Insertion ◽  
Scintillation Camera ◽  
Data Points ◽  
Indium 111 ◽  
Quantitative Uptake

Autologous platelets from mongrel dogs have been labeled with 200-400 μCi Indium-111 complexed to oxine using the technique of Thakur, McAfee and others. Intraarterial thrombogenesis was studied in vivo by advancing a polyethylene angiographic catheter from a femoral into a carotid artery, then serially imaging the catheter over periods of 0.5-3 hours by scintillation camera with interfaced computer. Quantitative uptake was derived from computer processing of the studies, and compared with in vitro In-111 counts and clot weight obtained at various times by catheter excision. Labeled platelets were injected prior to or at periods of 2 or 24 hours after catheter insertion in order to evaluate both forming and preformed thrombus. Platelet In-111 radioactivity was found to peak at 30-80 minutes in newly forming thrombus and to fall thereafter. In vitro In-111 activity correlated well with wet clot weight.In-111 (% inj. dose) = 0.00209 × (mgm clot) + 0.00091 (r = 0.882) (n = 24)In vivo correlation was also linear, but with a broader scatter of data points. At the peak, In-111 uptake was 0.06044). 019% of i.d. per cm of catheter by in vitro measurement, and clot weight was 27.9±5.6 mgm per cm. Preformed thrombus picked up substantially less of the label (2 hr: 0.017±0.011% i.d./cm; 24 hr: 0.00245).001% i.d./cm) (n=6) and was not imageable in vivo. The study documents the effectiveness of this new platelet radiolabel for quantitative in vivo scintigraphy of newly forming thrombus, which can be useful for comparison of different anti-thrombogenic regimens and different biomaterials. It also indicates, however, the problems that can be anticipated in attempting to image established thrombus in vivo.

scholarly journals Whole-BodyIn VivoMonitoring of Inflammatory Diseases Exploiting Human Interleukin 6-Luciferase Transgenic Mice

2015 ◽  
Vol 35 (20) ◽  
pp. 3590-3601 ◽  
Author(s):  
Makiko Hayashi ◽  
Jun Takai ◽  
Lei Yu ◽  
Hozumi Motohashi ◽  
Takashi Moriguchi ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Genetic Model ◽  
Imaging System ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Disease ◽  
Whole Body ◽  
Disease Models ◽  
Bac Clone ◽  
Inflammatory Status

Chronic inflammation underlies the pathological progression of various diseases, and thus many efforts have been made to quantitatively evaluate the inflammatory status of the diseases. In this study, we generated a highly sensitive inflammation-monitoring mouse system using a bacterial artificial chromosome (BAC) clone containing extended flanking sequences of the human interleukin 6 gene (hIL6) locus, in which the luciferase (Luc) reporter gene is integrated (hIL6-BAC-Luc). We successfully monitored lipopolysaccharide-induced systemic inflammation in various tissues of thehIL6-BAC-Lucmice using anin vivobioluminescence imaging system. When two chronic inflammatory disease models, i.e., a genetic model of atopic dermatitis and a model of experimental autoimmune encephalomyelitis (EAE), were applied to thehIL6-BAC-Lucmice, luciferase bioluminescence was specifically detected in the atopic skin lesion and central nervous system, respectively. Moreover, the Luc activities correlated well with the disease severity. Nrf2 is a master transcription factor that regulates antioxidative and detoxification enzyme genes. Upon EAE induction, the Nrf2-deficient mice crossed with thehIL6-BAC-Lucmice exhibited enhanced neurological symptoms concomitantly with robust luciferase luminescence in the neuronal tissue. Thus, whole-bodyin vivomonitoring using thehIL6-BAC-Luctransgenic system (WIM-6 system) provides a new and powerful diagnostic tool for real-timein vivomonitoring of inflammatory status in multiple different disease models.

Kinetics and Fate of 111Indium-Oxine Labelled Blood Platelets in Asplenic Subjects

1980 ◽  
Vol 44 (02) ◽  
pp. 100-104 ◽  
Author(s):  
Anthon duP Heyns ◽  
Matthys G Lötter ◽  
Philip N Badenhorst ◽  
Otto van Reenen ◽  
Henry Pieters ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Blood Platelets ◽  
Normal Subjects ◽  
Lower Limbs ◽  
Whole Body ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Survival Curves ◽  
Platelet Recovery ◽  
Body Activity

SummaryThe survival, tissue distribution and fate of 111Indium-oxine labelled autologous platelets was studied in four asplenic subjects with serial blood sampling, scintillation camera and computer-assisted imaging. Mean 111In-platelet recovery in the circulation was 89 ± 13% (± 1 SD). Platelet survival curves fitted a linear function best and was 238 ± 41 h. The shape of the survival curves of normal and asplenic subjects differed: in the asplenic subjects the curve was linear whereas that of normal subjects was significantly more curvilinear if analyzed by least squares computer fitting to a gamma function. Early hepatic 111In-activity was significant and transient and ascribed to the "collection injury". As labelled platelets disappeared from the circulation, 111Inactivity in the liver increased progressively and linearly to reach 42.5 ± 14.1 % of whole body activity at 240 h. Radioactivity also accumulated in the bone marrow, but could not be demonstrated in the vasculature of the lower limbs. These results would indicate that in asplenic subjects the major sites of destruction of senescent platelets are the liver and bone marrow.

Abstract 14935: Targeted Optical Molecular Imaging of Atheroma Calcification Using Novel Aldendronate-based Probe

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Dong Oh Kang ◽  
Yong Geun Lim ◽  
Joon Woo Song ◽  
Ye Hee Park ◽  
Hyun Jung Kim ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
High Resolution ◽  
Murine Model ◽  
Calcium Binding ◽  
Laser Scanning ◽  
Near Infrared ◽  
Imaging System ◽  
Whole Body ◽  
Imaging Results

Background/Objectives: Vascular spotty calcification is an actively regulated biological process resulting in plaque vulnerability. We investigated the feasibility of a novel alendronate-based near-infrared fluorescence (NIRF)-emitting probe to specifically target atherosclerotic calcification in a murine model in vivo using our customized high-resolution multichannel intravital molecular imaging system (IVFM). Methods/Results: We have fabricated a calcium-binding NIRF probe by chemically coupling alendronate, a specific targeting ligand, and NIRF-emitting Cy5.5 to the ends of azide-PEG-NHS ester (Al-Cy5.5). Prepared Al-Cy5.5 has high affinity for calcium phosphate-containing bone minerals. In vitro, Al-Cy5.5 specifically binds to RANKL-induced osteogenic-macrophages as compared to macrophages (p<0.01). On whole body fluorescence imaging to assess time-dependent excretion, NIRF signals remained visible up to 48 hrs. Then, in mice with calcified plaque induced by a combination diet of high-cholesterol and warfarin, Al-Cy5.5 (2.5 mg/kg) was intravenously injected. 48 hrs after administration, murine calcified atheroma was assessed using a customized high-resolution multichannel IVFM, which demonstrated highly enhanced NIRF signals in vivo in the calcified areas of murine carotid plaques (p<0.01, Figure). Ex vivo laser scanning fluorescence microscopic and immune-histological findings from the corresponding sister sections well corroborated the in vivo imaging results, which demonstrated the co-localization of NIRF signals with plaque calcifications (von-Kossa stain). Conclusions: Our novel calcification targeted probe, Al-Cy5.5, was able to selectively target atheroma calcification in vivo in a murine model as assessed by optical IVFM. This novel targetable strategy is expected to provide a promising theranostic basis for calcified high-risk plaques by integration with multimodal customized catheter imaging system.

First-in-human imaging of nanoparticle entrapped docetaxel (CPC634) in patients with advanced solid tumors using 89Zr-Df-CPC634 PET/CT.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3093-3093 ◽  
Author(s):  
Iris H.C. Miedema ◽  
Gerben J.C. Zwezerijnen ◽  
Daniela E. Oprea-Lager ◽  
Henk M.W. Verheul ◽  
Danielle J. Vugts ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Prolonged Exposure ◽  
Reticuloendothelial System ◽  
Whole Body ◽  
Tracer Injection ◽  
Epr Effect ◽  
Focal Uptake ◽  
Pet Ct ◽  
Tumor Retention

3093 Background: CPC634 is a nanoparticle entrapping docetaxel designed to improve tumor accumulation and tolerability compared to conventionally administered docetaxel by taking advantage of the presumed enhanced permeability and retention (EPR) effect. In vivo imaging with zirconium-89 (89Zr)-desferal (Df)-CPC634 will provide valuable information on its biodistribution and will quantify tumor retention. Methods: Patients with solid tumors not amenable to standard therapy received 37 MBq, 0.1-2mg of 89Zr-Df-CPC634 tracer and whole body PET/CT scans were obtained at 2, 24 and 96h post-injection (p.i.). Patients were administered CPC634 (60mg/m2) two weeks later followed by a second tracer injection and scans at 24 and 96h p.i. Biodistribution was quantified by delineating organs of interest and calculating mean %ID/kg. Visual tumor retention was defined as focal uptake in tumor lesions exceeding local background and quantified as standardized uptake peak values (SUVpeak) in volumes of interest. Results: Five patients were included. Biodistribution of 89Zr-Df-CPC634 showed significant retention in healthy liver, and spleen compared to lung (respectively 2.54, 1.61 and 0.56 mean %ID/kg at 96h p.i.), supporting apparent opsonization of nanoparticles in cells of the reticuloendothelial system. Visual retention was observed in 16/37 evaluable tumor lesions with the highest intensity at 96h p.i, compatible with the assumed EPR effect. Tumor retention showed intra- and interpatient heterogeneity, with a mean %ID/kg of 3.43 [1.14-9.32]. Pre-administering unlabeled CPC634 did not change the mean tumor retention of 89Zr-Df-CPC634 (at 96h p.i. mean 3.50 %ID/kg [1.64-9.97]), however, four additional lesions were visible in comparison to tracer only. Conclusions: The biodistribution of 89Zr-Df-CPC634 was consistent with a prolonged exposure of nanoparticle containing docetaxel. 89Zr-Df-CPC634 showed high retention in tumors confirming the EPR effect of these nanoparticle in humans, and supporting their further development for tumor targeting of therapeutic agents. A Phase II efficacy study in platinum resistant ovarian cancer (NTC03742713) is currently ongoing. Clinical trial information: NCT03712423.

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