In Vivo Dissolution Measurement with Indium-111 Summation Peak Ratios

1985 ◽  
Vol 74 (10) ◽  
pp. 1131-1133 ◽  
Author(s):  
Michael Jay ◽  
Michael A. Woodward ◽  
Kenneth R. Brouwer
Keyword(s):  
Indium 111 ◽  
In Vivo Dissolution

Preparation of a Viable Population of Indium-111- Labelled Human Blood Platelets

1979 ◽  
Vol 42 (05) ◽  
pp. 1473-1482 ◽  
Author(s):  
A Dup Heyns ◽  
P N Badenhorst ◽  
H Pieters ◽  
M G Lötter ◽  
P C Minnaar ◽  
...  
Keyword(s):  
Platelet Rich Plasma ◽  
Blood Platelets ◽  
Kinetic Studies ◽  
Physiological Saline ◽  
Human Platelets ◽  
Autologous Plasma ◽  
Platelet Suspension ◽  
Viable Population ◽  
Indium 111

SummaryFactors influencing labelling of human platelets with 111Indium-8-hydroxyquinoline ([111In]-oxine) in a physiological saline medium were investigated. The efficiency of labelling is influenced by time of incubation, concentration of oxine, and pH of the incubating medium. It was found that a viable platelet population could be labelled under the following conditions: (1) centrifugation of platelet rich plasma in polystyrene conical tubes at 800 g for 15 min; (2) resuspension of the platelet pellet in saline, pH 5.5; (3) incubating for 30 min at 22°C with [111In]-oxine at a concentration of 6.25 mg oxine/litre platelet suspension; (4) washing once with platelet poor autologous plasma (PPP); and (5) finally resuspending the platelets in PPP. The labelled platelets aggregated normally with collagen and ADP. Electron microscopy, done immediately after labelling, showed internal organelle reorganization characteristic of activated platelets. These ultrastructural features were reversible on incubation in PPP at 37°C for 30 min. The 111In is not released from aggregated platelets and the label does not elute from incubated platelets for at least five hr. We conclude that human platelets thus labelled are suitable for in vivo kinetic studies.

scholarly journals Humanization, Radiolabeling and Biodistribution Studies of an IgG1-Type Antibody Targeting Uncomplexed PSA for Theranostic Applications

2021 ◽  
Vol 14 (12) ◽  
pp. 1251
Author(s):  
Joanna Strand ◽  
Kjell Sjöström ◽  
Urpo J. Lamminmaki ◽  
Oskar Vilhelmsson Timmermand ◽  
Sven-Erik Strand ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Binding ◽  
Hek293 Cells ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Biodistribution Studies ◽  
Indium 111 ◽  
Hormone Refractory ◽  
Theranostic Applications

Metastatic castration-resistant prostate cancer is today incurable. Conventional imaging methods have limited detection, affecting their ability to give an accurate outcome prognosis, and current therapies for metastatic prostate cancer are insufficient. This inevitably leads to patients relapsing with castration-resistant prostate cancer. Targeting prostate-specific antigens whose expression is closely linked to the activity in the androgen receptor pathway, and thus the pathogenesis of prostate cancer, is a possible way to increase specificity and reduce off-target effects. We have humanized and evaluated radioimmunoconjugates of a previously murine antibody, m5A10, targeting PSA intended for theranostics of hormone-refractory prostate cancer. The humanized antibody h5A10 was expressed in mammalian HEK293 cells transfected with the nucleotide sequences for the heavy and light chains of the antibody. Cell culture medium was filtered and purified by Protein G chromatography, and the buffer was changed to PBS pH 7.4 by dialysis. Murine and humanized 5A10 were conjugated with p-SCN-Bn-CHX-A”-DTPA. Surface plasmon resonance was used to characterize the binding to PSA of the immunoconjugates. Immunoconjugates were labeled with either indium-111 or lutetium-177. Biodistribution studies of murine and humanized 5A10 were performed in mice with LNCaP xenografts. 5A10 was successfully humanized, and in vivo targeting showed specific binding in xenografts. The results thus give an excellent platform for further theranostic development of humanized 5A10 for clinical applications.

Locating And Monitoring The Activity Of Intracardiac Thrombi With Indium-111 Platelet Scintigraphy

1981 ◽  
Author(s):  
M D Ezekowitz ◽  
E O Smith ◽  
A C Cox ◽  
S W Herren ◽  
F B Taylor
Keyword(s):  
Artery Bypass ◽  
Inhibitory Response ◽  
Left Ventricular ◽  
Platelet Recovery ◽  
Platelet Scintigraphy ◽  
Indium 111 ◽  
Induced Aggregation ◽  
Intracardiac Thrombi

Indium-III is 2.8 day half-life gamma emitting radionuclide which is suitable for scintigraphic study and has been used to label platelets without causing significant attenuation of function. The purpose of this study was to utilize this technique for localization of left ventricular mural thrombi in patients with regional LV dysfunction. The patient population consisted of 55 patients between the ages of 24 and 77 (53.4 ± 11.3, mean ± 1SD). Twenty-four required coronary artery bypass surgery with aneurysmectomy for intractable angina and/or heart failure. This provided an opportunity to validate the preoperative findings at surgery. Platelets were separated from 43 ml blood in ACD solution by centrifugation and were labelled in ACD:saline (1:7) solution at a pH of 6.5-7.0. A total of 3.8 ± 2.9 × 109 (mean ± 1SD) platelets labelled with 451.9 ± 111.6 μCi with a final labelling efficiency of 72.1±14.1% were injected IV. Platelet recovery at 15 minutes was 51.1 ± 17.7% (mean ± 1SD). EM studies before and after labelling showed no morphological change due to the labelling procedure. Aggregation of platelets in response to ADP and collagen was not altered significantly during the labelling process. Patients on aspirin showed the expected inhibitory effect of aspirin on collagen and ADP induced aggregation. Patients were imaged in multiple views on at least alternate days for a maximum of 8 days. Seventeen had positive studies. In those patients in which surgical confirmation of the scintigraphic studies was possible, a sensitivity of 72% and specificity of 100% was found. We conclude that: 1) Indium-111 platelet scintigraphy promises to be a reliable method of identifying intracardiac thrombi. 2) It may also be useful in monitoring thrombus activity in vivo. 3) Patients on aspirin incorporated platelets onto the thrombus surface in spite of showing the expected inhibitory response to ADP and collagen induced aggregation in vitro.

scholarly journals Physiologically Relevant In Vitro-In Vivo Correlation (IVIVC) Approach for Sildenafil with Site-Dependent Dissolution

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 251 ◽  
Author(s):  
Tae Hwan Kim ◽  
Soyoung Shin ◽  
Seok Won Jeong ◽  
Jong Bong Lee ◽  
Beom Soo Shin
Keyword(s):  
Dissolution Kinetics ◽  
Immediate Release ◽  
Relative Bioavailability ◽  
Wet Granulation ◽  
Population Pharmacokinetic ◽  
Beagle Dogs ◽  
Concentration Time ◽  
In Vivo Dissolution

This study aimed to establish a physiologically relevant in vitro-in vivo correlation (IVIVC) model reflecting site-dependent dissolution kinetics for sildenafil based on population-pharmacokinetic (POP-PK) modeling. An immediate release (IR, 20 mg) and three sustained release (SR, 60 mg) sildenafil tablets were prepared by wet granulation method. In vitro dissolutions were determined by the paddle method at pH 1.2, 4.5, and 6.8 media. The in vivo pharmacokinetics were assessed after oral administration of the prepared IR and SR formulations to Beagle dogs (n = 12). The dissolution of sildenafil from SR formulations was incomplete at pH 6.8, which was not observed at pH 1.2 and pH 4.5. The relative bioavailability was reduced with the decrease of the dissolution rate. Moreover, secondary peaks were observed in the plasma concentration-time curves, which may result from site-dependent dissolution. Thus, a POP-PK model was developed to reflect the site-dependent dissolution by separately describing the dissolution and absorption processes, which allowed for estimation of the in vivo dissolution of sildenafil. Finally, an IVIVC was established and validated by correlating the in vitro and in vivo dissolution rates. The present approach may be applied to establish IVIVC for various drugs with complex dissolution kinetics for the development of new formulations.

Comparison of in vivo dissolution processes in hydroxyapatite and silicon-substituted hydroxyapatite bioceramics

Biomaterials ◽  
2003 ◽  
Vol 24 (25) ◽  
pp. 4609-4620 ◽  
Author(s):  
A.E. Porter ◽  
N. Patel ◽  
J.N. Skepper ◽  
S.M. Best ◽  
W. Bonfield
Keyword(s):  
In Vivo Dissolution

A Non-Invasive Method For Measuring Platelet Aggregation In Vivo

1981 ◽  
Author(s):  
J Morley ◽  
P M Hoyle ◽  
J Leyton ◽  
O J Davies
Keyword(s):  
Graphical Form ◽  
Functional Disturbance ◽  
Non Invasive ◽  
Hind Limbs ◽  
Minute Period ◽  
Invasive Method ◽  
Crystal Scintillation ◽  
Indium 111 ◽  
Aggregation And Disaggregation

In experimental animals, intravenous injection of ADP produces platelet accumulation in the lungs, together with thrombocytopenia. Since platelets can be isotopically labelled without gross functional disturbance, we have sought to develop a method for measurement of aggregation and disaggregation of labelled platelets in vivo.Guinea-pig platelets are labelled with Indium-111 and injected into narcotised animals (Sagital, 37 mg/kg). Two collimated crystal scintillation probes are used to monitor the thoracic region (heart and lung) (Cl) and the vascular compartment (hind limbs) (C2). An indwelling cannula (25 SWG) is inserted into a foot vein and kept patent by small volumes of heparin (100 u/ml). Intravenous ADP (10 mg/kg) causes transient accumulation of platelets within the lung, as well as thrombocytopenia, within a two minute period. During a response, counts are monitored from both probes and retained in a dedicated microcomputer, so as to permit rapid display of results in tabular and graphical form. Usually, ninety consecutive 4 sec. counts are recorded, results being expressed both as a paired difference (C1-C2) and as a ratio (C1/C2). Repeated challenge can be made with ADP and a dose-related response is obtained over the range 10-30 mg/kg. Treatment with sulphinpyrazone or prostacyclin inhibits aggregation.

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