scholarly journals Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 4012
Author(s):  
Romain Eychenne ◽  
Christelle Bouvry ◽  
Mickael Bourgeois ◽  
Pascal Loyer ◽  
Eric Benoist ◽  
...  
Keyword(s):  
Half Life ◽  
Therapeutic Strategy ◽  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Whole Body ◽  
Pharmacokinetic Properties ◽  
Indium 111 ◽  
The Stability ◽  
Gallium 68 ◽  
Metabolic Radiotherapy

Identified in 1973, somatostatin (SST) is a cyclic hormone peptide with a short biological half-life. Somatostatin receptors (SSTRs) are widely expressed in the whole body, with five subtypes described. The interaction between SST and its receptors leads to the internalization of the ligand–receptor complex and triggers different cellular signaling pathways. Interestingly, the expression of SSTRs is significantly enhanced in many solid tumors, especially gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). Thus, somatostatin analogs (SSAs) have been developed to improve the stability of the endogenous ligand and so extend its half-life. Radiolabeled analogs have been developed with several radioelements such as indium-111, technetium-99 m, and recently gallium-68, fluorine-18, and copper-64, to visualize the distribution of receptor overexpression in tumors. Internal metabolic radiotherapy is also used as a therapeutic strategy (e.g., using yttrium-90, lutetium-177, and actinium-225). With some radiopharmaceuticals now used in clinical practice, somatostatin analogs developed for imaging and therapy are an example of the concept of personalized medicine with a theranostic approach. Here, we review the development of these analogs, from the well-established and authorized ones to the most recently developed radiotracers, which have better pharmacokinetic properties and demonstrate increased efficacy and safety, as well as the search for new clinical indications.

Indium-111-DTPA-octreotide Scintigraphy Modulation by Treatment with Unlabelled Somatostatin Analogue in Smali-Cell Lung Cancer

1995 ◽  
Vol 81 (2) ◽  
pp. 125-127 ◽  
Author(s):  
Enzo Soresi ◽  
Emilio Bombardieri ◽  
Arturo Chiti ◽  
Roberto Boffi ◽  
Giovanni Invernizzi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Lung Cancer ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Whole Body ◽  
Somatostatin Analogue ◽  
Normal Tissues ◽  
Before And After ◽  
Octreotide Scintigraphy ◽  
Indium 111

Aims and background Small-cell lung cancer (SCLC) tissue expresses somatostatin receptors and can be visualized by means of the indium-111-labelled somatostatin analogue DTPA-D-Pheoctreotide. The aim of the study was to investigate whether treatment with a cold somatostatin analogue can affect the imaging of somatostatin receptor scintigraphy. Methods Three patients with SCLC were treated with 200 μg of cold octreotide three times a day subcutaneously for 7 days. Whole body and planar scintigraphy was performed before and after the treatment. Results 111In-DTPA-octreotide uptake was increased in cancer lesions, whereas fixation in normal tissues (liver, spleen, kidneys) decreased. Conclusions This is the first demonstration of an enhancement of SCLC imaging following unlabelled somatostatin analogue administration. Similar results have been described by other authors in a limited number of carcinoid tumors.

Kinetics of Various 99mTc-Sn-Pyrophosphate Compounds in the Rat

1977 ◽  
Vol 16 (04) ◽  
pp. 157-162 ◽  
Author(s):  
C. Schümichen ◽  
B. Mackenbrock ◽  
G. Hoffmann
Keyword(s):  
Normal Saline ◽  
Half Life ◽  
Compound A ◽  
Short Half Life ◽  
Low Concentrations ◽  
The Stability ◽  
Kinetics Of ◽  
In Vitro Stability

SummaryThe bone-seeking 99mTc-Sn-pyrophosphate compound (compound A) was diluted both in vitro and in vivo and proved to be unstable both in vitro and in vivo. However, stability was much better in vivo than in vitro and thus the in vitro stability of compound A after dilution in various mediums could be followed up by a consecutive evaluation of the in vivo distribution in the rat. After dilution in neutral normal saline compound A is metastable and after a short half-life it is transformed into the other 99mTc-Sn-pyrophosphate compound A is metastable and after a short half-life in bone but in the kidneys. After dilution in normal saline of low pH and in buffering solutions the stability of compound A is increased. In human plasma compound A is relatively stable but not in plasma water. When compound B is formed in a buffering solution, uptake in the kidneys and excretion in urine is lowered and blood concentration increased.It is assumed that the association of protons to compound A will increase its stability at low concentrations while that to compound B will lead to a strong protein bond in plasma. It is concluded that compound A will not be stable in vivo because of a lack of stability in the extravascular space, and that the protein bond in plasma will be a measure of its in vivo stability.

In-vitro Kinetic Hydrolysis Study of Metronidazole Derivatives with Carvacrol and Eugenol Using Validated RP-HPLC Method

2020 ◽  
Vol 16 ◽  
Author(s):  
M. Alarjah
Keyword(s):  
Half Life ◽  
Hplc Method ◽  
Hydrolysis Rate ◽  
First Order ◽  
First Order Kinetics ◽  
Rp Hplc ◽  
Pharmacokinetic Properties ◽  
Pseudo First Order ◽  
Kinetic Hydrolysis

Background: Prodrugs principle is widely used to improve the pharmacological and pharmacokinetic properties of some active drugs. Much effort was made to develop metronidazole prodrugs to enhance antibacterial activity and or to improve pharmacokinetic properties of the molecule or to lower the adverse effects of metronidazole. Objective: In this work, the pharmacokinetic properties of some of monoterpenes and eugenol pro metronidazole molecules that were developed earlier were evaluated in-vitro. The kinetic hydrolysis rate constants and half-life time estimation of the new metronidazole derivatives were calculated using the validated RP-HPLC method. Method: Chromatographic analysis was done using Zorbbax Eclipse eXtra Dense Bonding (XDB)-C18 column of dimensions (250 mm, 4.6 mm, 5 μm), at ambient column temperature. The mobile phase was a mixture of sodium dihydrogen phosphate buffer of pH 4.5 and methanol in gradient elution, at 1ml/min flow rate. The method was fully validated according to the International Council for Harmonization (ICH) guidelines. The hydrolysis process carried out in an acidic buffer pH 1.2 and in an alkaline buffer pH 7.4 in a thermostatic bath at 37ºC. Results: The results followed pseudo-first-order kinetics. All metronidazole prodrugs were stable in the acidic pH, while they were hydrolysed in the alkaline buffer within a few hours (6-8 hr). The rate constant and half-life values were calculated, and their values were found to be 0.082- 0.117 hr-1 and 5.9- 8.5 hr., respectively. Conclusion: The developed method was accurate, sensitive, and selective for the prodrugs. For most of the prodrugs, the hydrolysis followed pseudo-first-order kinetics; the method might be utilised to conduct an in-vivo study for the metronidazole derivatives with monoterpenes and eugenol.

scholarly journals Systemic exposure following intravitreal administration of therapeutic agents: an integrated pharmacokinetic approach. 2. THR-687

2021 ◽  
Author(s):  
Marc Vanhove ◽  
Jean-Marc Wagner ◽  
Bernard Noppen ◽  
Bart Jonckx ◽  
Elke Vermassen ◽  
...  
Keyword(s):  
General Circulation ◽  
Pharmacokinetic Model ◽  
Systemic Exposure ◽  
Age Related Macular Degeneration ◽  
Whole Body ◽  
Pharmacological Agents ◽  
Age Related ◽  
Pharmacokinetic Properties ◽  
High Concentrations ◽  
Systemic Compartment

AbstractIntravitreal (IVT) injection remains the preferred administration route of pharmacological agents intended for the treatment of back of the eye diseases such as diabetic macular edema (DME) and neovascular age-related macular degeneration (nvAMD). The procedure enables drugs to be delivered locally at high concentrations whilst limiting whole body exposure and associated risk of systemic adverse events. Nevertheless, intravitreally-delivered drugs do enter the general circulation and achieving an accurate understanding of systemic exposure is pivotal for the evaluation and development of drugs administered in the eye. We report here the full pharmacokinetic properties of THR-687, a pan RGD integrin antagonist currently in clinical development for the treatment of DME, in both rabbit and minipig. Pharmacokinetic characterization included description of vitreal elimination, of systemic pharmacokinetics, and of systemic exposure following IVT administration. For the latter, we present a novel pharmacokinetic model that assumes clear partition between the vitreous humor compartment itself where the drug is administered and the central systemic compartment. We also propose an analytical solution to the system of differential equations that represent the pharmacokinetic model, thereby allowing data analysis with standard nonlinear regression analysis. The model accurately describes circulating levels of THR-687 following IVT administration in relevant animal models, and we suggest that this approach is relevant to a range of drugs and analysis of subsequent systemic exposure.

Stability as a constraint in sagittal plane human force exertion modeling

1998 ◽  
Vol 1 (1) ◽  
pp. 23-39
Author(s):  
Carter J. Kerk ◽  
Don B. Chaffin ◽  
W. Monroe Keyserling
Keyword(s):  
Muscle Strength ◽  
Ankle Joint ◽  
Coefficient Of Friction ◽  
Sagittal Plane ◽  
Biomechanical Model ◽  
Whole Body ◽  
The Stability ◽  
Joint Center ◽  
Static Conditions ◽  
Stability Limits

The stability constraints of a two-dimensional static human force exertion capability model (2DHFEC) were evaluated with subjects of varying anthropometry and strength capabilities performing manual exertions. The biomechanical model comprehensively estimated human force exertion capability under sagittally symmetric static conditions using constraints from three classes: stability, joint muscle strength, and coefficient of friction. Experimental results showed the concept of stability must be considered with joint muscle strength capability and coefficient of friction in predicting hand force exertion capability. Information was gained concerning foot modeling parameters as they affect whole-body stability. Findings indicated that stability limits should be placed approximately 37 % the ankle joint center to the posterior-most point of the foot and 130 % the distance from the ankle joint center to the maximal medial protuberance (the ball of the foot). 2DHFEC provided improvements over existing models, especially where horizontal push/pull forces create balance concerns.

scholarly journals Investigation of the Stability of Yeast rad52 Mutant Proteins Uncovers Post-translational and Transcriptional Regulation of Rad52p

Genetics ◽  
2003 ◽  
Vol 163 (1) ◽  
pp. 91-101 ◽  
Author(s):  
Erin N Asleson ◽  
Dennis M Livingston
Keyword(s):  
Half Life ◽  
Translational Regulation ◽  
Cellular Level ◽  
Missense Mutations ◽  
Wild Type ◽  
Mutant Proteins ◽  
Gal1 Promoter ◽  
Rad52 Protein ◽  
The Stability ◽  
Mutant Forms

Abstract We investigated the stability of the Saccharomyces cerevisiae Rad52 protein to learn how a cell controls its quantity and longevity. We measured the cellular levels of wild-type and mutant forms of Rad52p when expressed from the RAD52 promoter and the half-lives of the various forms of Rad52p when expressed from the GAL1 promoter. The wild-type protein has a half-life of 15 min. rad52 mutations variably affect the cellular levels of the protein products, and these levels correlate with the measured half-lives. While missense mutations in the N terminus of the protein drastically reduce the cellular levels of the mutant proteins, two mutations—one a deletion of amino acids 210-327 and the other a missense mutation of residue 235—increase the cellular level and half-life more than twofold. These results suggest that Rad52p is subject to post-translational regulation. Proteasomal mutations have no effect on Rad52p half-life but increase the amount of RAD52 message. In contrast to Rad52p, the half-life of Rad51p is >2 hr, and RAD51 expression is unaffected by proteasomal mutations. These differences between Rad52p and Rad51p suggest differential regulation of two proteins that interact in recombinational repair.

Photoinhibition of Electron Transport Activity of Photosystem II in Isolated Thylakoids Studied by Thermoluminescence and Delayed Luminescence

1988 ◽  
Vol 43 (11-12) ◽  
pp. 871-876 ◽  
Author(s):  
Imre Vass ◽  
Narendranath Mohanty ◽  
Sándor Demeter
Keyword(s):  
Electron Transport ◽  
Photosystem Ii ◽  
Photosystem I ◽  
Half Life ◽  
Delayed Luminescence ◽  
Transport Activity ◽  
Primary Target ◽  
Electron Transport Activity ◽  
The Stability ◽  
Spinach Thylakoids

Abstract The effect of photoinhibition on the primary (QA) and secondary (QB) quinone acceptors of photosystem I I was investigated in isolated spinach thylakoids by the methods of thermoluminescence and delayed luminescence. The amplitudes of the Q (at about 2 °C) and B (at about 30 °C) thermoluminescence bands which are associated with the recombination of the S2QA- and S2QB charge pairs, respectively, exhibited parallel decay courses during photoinhibitory treatment. Similarly, the amplitudes of the flash-induced delayed luminescence components ascribed to the recombination of S20A and S2OB charge pairs and having half life-times of about 3 s and 30 s, respectively, declined in parallel with the amplitudes of the corresponding Q and B thermoluminescence bands. The course of inhibition of thermoluminescence and delayed luminescence intensity was parallel with that of the rate of oxygen evolution. The peak positions of the B and Q thermoluminescence bands as well as the half life-times of the corresponding delayed luminescence components were not affected by photoinhibition. These results indicate that in isolated thylakoids neither the amount nor the stability of the reduced OB acceptor is preferentially decreased by photoinhibition. We conclude that either the primary target of photodamage is located before the O b binding site in the reaction center of photosystem II or QA and OB undergo simultaneous damage.

Rate of loss of radioiron from mouse and man

1960 ◽  
Vol 198 (4) ◽  
pp. 784-786 ◽  
Author(s):  
John D. Bonnet ◽  
Alan L. Orvis ◽  
Albert B. Hagedorn ◽  
Charles A. Owen
Keyword(s):  
Life Span ◽  
Half Life ◽  
Whole Body ◽  
Entire Body ◽  
Rapid Loss ◽  
Male And Female ◽  
Female Mice ◽  
Steady Rate ◽  
Normal Man ◽  
The Difference

Forty-two male and female mice, 8 weeks old, were given radioiron (Fe59) in doses of 0.006–0.1 µc, containing 0.013–0.17 µg of iron, by intraperitoneal or intravenous routes. Assays of the radioactivity of the whole body revealed an initial rapid loss of Fe59 (15–20%) lasting about 6 days. Thereafter the Fe59 left the mice at a steady rate of 0.39%/day (half-life 180 days). One 34-year-old normal man was given 10.6 µc of Fe59, containing 8.2 µg of iron, intravenously. Based on counts from the entire body, the biologic rate of loss of the Fe59 was about 0.14%/day (half-life 500 days), and there was little or no initial loss such as occurred in the mouse. The Fe59 in the circulating erythrocytes was essentially unchanged for the first 3 months. It then fell to a new level of about 90% of the previous one; the mid-point of the fall was about 120 days after the administration of the radioiron. The difference in the rates of loss of radioiron from mice and man seems to be related primarily to the life span of the circulating red cells.

scholarly journals A Flexible Synthesis of 68Ga-Labeled Carbonic Anhydrase IX (CAIX)-Targeted Molecules via CBT/1,2-Aminothiol Click Reaction

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 23 ◽  
Author(s):  
Kuo-Ting Chen ◽  
Kevin Nguyen ◽  
Christian Ieritano ◽  
Feng Gao ◽  
Yann Seimbille
Keyword(s):  
Carbonic Anhydrase ◽  
Half Life ◽  
Reaction Rate ◽  
Click Reaction ◽  
Tumor Hypoxia ◽  
Carbonic Anhydrase Ix ◽  
Reaction Conditions ◽  
Positron Emitter ◽  
Radiochemical Yields ◽  
Gallium 68

We herein describe a flexible synthesis of a small library of 68Ga-labeled CAIX-targeted molecules via an orthogonal 2-cyanobenzothiazole (CBT)/1,2-aminothiol click reaction. Three novel CBT-functionalized chelators (1–3) were successfully synthesized and labeled with the positron emitter gallium-68. Cross-ligation between the pre-labeled bifunctional chelators (BFCs) and the 1,2-aminothiol-acetazolamide derivatives (8 and 9) yielded six new 68Ga-labeled CAIX ligands with high radiochemical yields. The click reaction conditions were optimized to improve the reaction rate for applications with short half-life radionuclides. Overall, our methodology allows for a simple and efficient radiosynthetic route to produce a variety of 68Ga-labeled imaging agents for tumor hypoxia.

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