scholarly journals Radiopharmaceutical Validation for Clinical Use

2021 ◽  
Vol 11 ◽  
Author(s):  
Charles A. Kunos ◽  
Rodney Howells ◽  
Aman Chauhan ◽  
Zin W. Myint ◽  
Mark E. Bernard ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Early Phase ◽  
Target Antigen ◽  
Clinical Use ◽  
Biodistribution Studies ◽  
Early Phase Trials ◽  
Near Term ◽  
Four Levels

Radiopharmaceuticals are reemerging as attractive anticancer agents, but there are no universally adopted guidelines or standardized procedures for evaluating agent validity before early-phase trial implementation. To validate a radiopharmaceutical, it is desirous for the radiopharmaceutical to be specific, selective, and deliverable against tumors of a given, molecularly defined cancer for which it is intended to treat. In this article, we discuss four levels of evidence—target antigen immunohistochemistry, in vitro and in vivo preclinical experiments, animal biodistribution and dosimetry studies, and first-in-human microdose biodistribution studies—that might be used to justify oncology therapeutic radiopharmaceuticals in a drug-development sequence involving early-phase trials. We discuss common practices for validating radiopharmaceuticals for clinical use, everyday pitfalls, and commonplace operationalizing steps for radiopharmaceutical early-phase trials. We anticipate in the near-term that radiopharmaceutical trials will become a larger proportion of the National Cancer Institute Cancer Therapy Evaluation Program (CTEP) portfolio.

scholarly journals PLANT-DERIVED CHEMOTHERAPEUTICS DRUGS FOR CANCER CHEMOTHERAPY

2021 ◽  
Vol 1 (1) ◽  
pp. 28-37
Author(s):  
Alexandra Dragoi ◽  
Oana Alexandru
Keyword(s):  
Anticancer Agents ◽  
Natural Compounds ◽  
Clinical Use ◽  
Vinca Alkaloids ◽  
Chemotherapeutic Drugs ◽  
Malignant Cells ◽  
In Vivo Experiments ◽  
Whole Plant

Cancer chemotherapeutic drugs acts in different manner to kill malignant cells. Most of the anticancer drugs available in clinical practice to treat cancer patients, are natural products including whole plant extract, crude plant extracts, isolated constituents, plant –based drug formulations etc. These natural compounds have been a basis for the development of several drugs against cancer. Agents such as topotecan, taxol, vinca alkaloids (vincristine, vinblastine, vinorelbine and vindesine), are important anticancer agents in widespread clinical use. Other agents, such as combretastatin, flavopiridol, betulinic acid were shown to have anti-tumor effects in both in vitro and in vivo experiments. In this review, we aim to make a brief description of classical plant-derived chemotherapeutics drugs and also to highlight the importance of these natural compounds in the development of new potential drugs in cancer treatment.

scholarly journals 124I-Radiolabeling of a Au(III)-NHC Complex for in Vivo Biodistribution Studies

2020 ◽  
Author(s):  
Federica Guarra ◽  
Alessio Terenzi ◽  
Christine Pirker ◽  
Rossana Passannante ◽  
Dina Baier ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Direct Evidence ◽  
Heterocyclic Carbenes ◽  
Emission Tomography ◽  
Direct Oxidation ◽  
In Vivo Biodistribution ◽  
Biodistribution Studies ◽  
Positron Emission

Au(III) complexes with N-Heterocyclic Carbenes (NHCs) ligands have shown remarkable potential as anticancer agents, yet their fate in vivo has not been thoroughly examined and understood. Herein we report on the synthesis of new Au(III)-NHC complexes via direct oxidation with radioactive [124I]I2 as a valuable strategy to monitor the in vivo biodistribution of this class of compounds using positron emission tomography (PET) and, in combination with in vitro analyses, to provide direct evidence of the importance of Au(III)-to-Au(I) reduction for achieving full anticancer activity.

scholarly journals 124I-Radiolabeling of a Au(III)-NHC Complex for in Vivo Biodistribution Studies

2020 ◽  
Author(s):  
Federica Guarra ◽  
Alessio Terenzi ◽  
Christine Pirker ◽  
Rossana Passannante ◽  
Dina Baier ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Direct Evidence ◽  
Heterocyclic Carbenes ◽  
Emission Tomography ◽  
Direct Oxidation ◽  
In Vivo Biodistribution ◽  
Biodistribution Studies ◽  
Positron Emission

Au(III) complexes with N-Heterocyclic Carbenes (NHCs) ligands have shown remarkable potential as anticancer agents, yet their fate in vivo has not been thoroughly examined and understood. Herein we report on the synthesis of new Au(III)-NHC complexes via direct oxidation with radioactive [124I]I2 as a valuable strategy to monitor the in vivo biodistribution of this class of compounds using positron emission tomography (PET) and, in combination with in vitro analyses, to provide direct evidence of the importance of Au(III)-to-Au(I) reduction for achieving full anticancer activity.

scholarly journals Organometallic iron complexes as potential cancer therapeutics.

2014 ◽  
Vol 61 (4) ◽  
Author(s):  
Gabriela Mojžišová ◽  
Ján Mojžiš ◽  
Janka Vašková
Keyword(s):  
Anticancer Agents ◽  
Acquired Resistance ◽  
Cancer Therapeutics ◽  
Iron Complexes ◽  
Cytotoxic Agents ◽  
In Vitro Tests ◽  
Clinical Use ◽  
In Vivo Experiments

Metal-containing drugs have long been used for medicinal purposes in more or less empirical way. The potential of these anticancer agents has only been fully realised and explored since the discovery of the biological activity of cisplatin. Cisplatin and carboplatin have been two of the most successful anti-cancer agents ever developed, and are currently used to treat ovarian, lung and testicular cancers. They share certain side effects, so their clinical use is severely limited by dose-limiting toxicity. Inherent or acquired resistance is a second problem often associated with platinum-based drugs, with further limits of their clinical use. These problems have prompted chemists to employ different strategies in development of the new metal-based anticancer agents with different mechanisms of action. There are various metal complexes still under development and investigation for the future cancer treatment use. In the search for novel bio-organometallic molecules, iron containing anti-tumoral agents are enjoying an increasing interest and appear very promising as the potential drug candidates. Iron, as an essential cofactor in a number of enzymes and physiological processes, may be less toxic than non essential metals, such as platinum. Up to now, some of iron complexes have been tested as cytotoxic agents and found to be endowed with an antitumor activity in several in vitro tests (on cultured cancer cell lines) and few in vivo experiments (e. g. on Ehrlich's ascites carcinoma). Although the precise molecular mechanism is yet to be defined, a number of observations suggest that the reactive oxygen species can play important role in iron-induced cytotoxicty. This review covers some relevant examples of research on the novel iron complexes.

scholarly journals 124I-Radiolabeling of a Au(III)-NHC Complex for in Vivo Biodistribution Studies

2020 ◽  
Author(s):  
Federica Guarra ◽  
Alessio Terenzi ◽  
Christine Pirker ◽  
Rossana Passannante ◽  
Dina Baier ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Direct Evidence ◽  
Heterocyclic Carbenes ◽  
Emission Tomography ◽  
Direct Oxidation ◽  
In Vivo Biodistribution ◽  
Biodistribution Studies ◽  
Positron Emission

Au(III) complexes with N-Heterocyclic Carbenes (NHCs) ligands have shown remarkable potential as anticancer agents, yet their fate in vivo has not been thoroughly examined and understood. Herein we report on the synthesis of new Au(III)-NHC complexes via direct oxidation with radioactive [124I]I2 as a valuable strategy to monitor the in vivo biodistribution of this class of compounds using positron emission tomography (PET) and, in combination with in vitro analyses, to provide direct evidence of the importance of Au(III)-to-Au(I) reduction for achieving full anticancer activity.

scholarly journals Genetics of Streptomyces rimosus, the Oxytetracycline Producer

2006 ◽  
Vol 70 (3) ◽  
pp. 704-728 ◽  
Author(s):  
Hrvoje Petković ◽  
John Cullum ◽  
Daslav Hranueli ◽  
Iain S. Hunter ◽  
Nataša Perić-Concha ◽  
...  
Keyword(s):  
Genetic Instability ◽  
Clinical Use ◽  
Streptomyces Rimosus ◽  
Emerging Infections ◽  
Tetracycline Antibiotics ◽  
Genetic Manipulations ◽  
Near Term

SUMMARY From a genetic standpoint, Streptomyces rimosus is arguably the best-characterized industrial streptomycete as the producer of oxytetracycline and other tetracycline antibiotics. Although resistance to these antibiotics has reduced their clinical use in recent years, tetracyclines have an increasing role in the treatment of emerging infections and noninfective diseases. Procedures for in vivo and in vitro genetic manipulations in S. rimosus have been developed since the 1950s and applied to study the genetic instability of S. rimosus strains and for the molecular cloning and characterization of genes involved in oxytetracycline biosynthesis. Recent advances in the methodology of genome sequencing bring the realistic prospect of obtaining the genome sequence of S. rimosus in the near term.

A Comparison of the in Vitro and in Vivo Thrombogenic Activity of Factor IX Concentrates Using Stasis (Wessler) and Non-Stasis Rabbit Models

1980 ◽  
Vol 44 (02) ◽  
pp. 081-086 ◽  
Author(s):  
C V Prowse ◽  
A E Williams
Keyword(s):  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Factor Ix ◽  
Coagulation System ◽  
In Vitro Tests ◽  
Clinical Use ◽  
Low Activity

SummaryThe thrombogenic effects of selected factor IX concentrates were evaluated in two rabbit models; the Wessler stasis model and a novel non-stasis model. Concentrates active in either the NAPTT or TGt50 in vitro tests of potential thrombogenicity, or both, caused thrombus formation in the Wessler technique and activation of the coagulation system in the non-stasis model. A concentrate with low activity in both in vitro tests did not have thrombogenic effects in vivo, at the chosen dose. Results in the non-stasis model suggested that the thrombogenic effects of factor IX concentrates may occur by at least two mechanisms. A concentrate prepared from platelet-rich plasma and a pyrogenic concentrate were also tested and found to have no thrombogenic effect in vivo.These studies justify the use of the NAPTT and TGt50 in vitro tests for the screening of factor IX concentrates prior to clinical use.

Toxicity of Heparinoids, with Special Reference to the Precipitation of Fibrinogen

1964 ◽  
Vol 12 (01) ◽  
pp. 232-261 ◽  
Author(s):  
S Sasaki ◽  
T Takemoto ◽  
S Oka
Keyword(s):  
Molecular Weight ◽  
Dextran Sulfate ◽  
Anticoagulant Activity ◽  
Molecular Structures ◽  
Severe Reaction ◽  
Clinical Use ◽  
Molecular Weights ◽  
Close Relationship

SummaryTo demonstrate whether the intravascular precipitation of fibrinogen is responsible for the toxicity of heparinoid, the relation between the toxicity of heparinoid in vivo and the precipitation of fibrinogen in vitro was investigated, using dextran sulfate of various molecular weights and various heparinoids.1. There are close relationships between the molecular weight of dextran sulfate, its toxicity, and the quantity of fibrinogen precipitated.2. The close relationship between the toxicity and the precipitation of fibrinogen found for dextran sulfate holds good for other heparinoids regardless of their molecular structures.3. Histological findings suggest strongly that the pathological changes produced with dextran sulfate are caused primarily by the intravascular precipitates with occlusion of the capillaries.From these facts, it is concluded that the precipitates of fibrinogen with heparinoid may be the cause or at least the major cause of the toxicity of heparinoid.4. The most suitable molecular weight of dextran sulfate for clinical use was found to be 5,300 ~ 6,700, from the maximum value of the product (LD50 · Anticoagulant activity). This product (LD50 · Anticoagulant activity) can be employed generally to assess the comparative merits of various heparinoids.5. Clinical use of the dextran sulfate prepared on this basis gave satisfactory results. No severe reaction was observed. However, two delayed reactions, alopecia and thrombocytopenia, were observed. These two reactions seem to come from the cause other than intravascular precipitation.

Inhibition of Fibrinolysis and Fibrinogenolysis in Man: Comparison of ε-Aminocaproic Acid and Kallikrein Inhibitor

1963 ◽  
Vol 10 (01) ◽  
pp. 106-119 ◽  
Author(s):  
E Beck ◽  
R Schmutzler ◽  
F Duckert ◽  
Keyword(s):  
Aminocaproic Acid ◽  
Side Reactions ◽  
In Vitro Tests ◽  
Factor V ◽  
Clinical Use ◽  
Strong Inhibitor ◽  
Kallikrein Inhibitor ◽  
Therapeutic Possibilities

SummaryInhibitor of kallikrein and trypsin (KI) extracted from bovine parotis was compared with ε-aminocaproic acid (EACA): both substances inhibit fibrinolysis induced with streptokinase. EACA is a strong inhibitor of fibrinolysis in concentrations higher than 0, 1 mg per ml plasma. The same amount and higher concentrations are not able to inhibit completely the proteolytic-side reactions of fibrinolysis (fibrinogenolysis, diminution of factor V, rise of fibrin-polymerization-inhibitors). KI inhibits well proteolysis of plasma components in concentrations higher than 2,5 units per ml plasma. Much higher amounts of KI are needed to inhibit fibrinolysis as demonstrated by our in vivo and in vitro tests.Combination of the two substances for clinical use is suggested. Therapeutic possibilities are discussed.

Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan
Keyword(s):  
Side Effects ◽  
Medicinal Plants ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Psidium Guajava ◽  
Current Status ◽  
Future Perspective ◽  
Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

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