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Translation of Radiopharmaceuticals
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Pedro Fragoso Costa, Latifa Rbah-Vidal, An Aerts, Fijs W.B. van Leeuwen, Margret Schottelius
For example, a strong hepatic and biliary uptake of a radiotracer indicates a hepatobiliary excretion of radioactivity, but also some risk of hepatic radiotoxicity. Thus, in addition to the evaluation of metabolism and excretion rates, the excretory tissues (liver, kidney, bladder) and all high uptake tissues are oftentimes subjected to macroscopic and histological analysis, to confirm the absence of abnormalities or to predict the radiotoxicity. Indeed, biodistribution studies can also be used to calculate the effective dose and thus the dosimetry in each of the target tissues.
Gold Nanoparticles as Promising Agents for Cancer Therapy
Published in Hala Gali-Muhtasib, Racha Chouaib, Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
Nadine Karaki, Hassan Hajj Ali, Assem El Kak
Nanoparticles-based drug delivery systems were primarily created to ensure the delivery of the drug to its specific target site without affecting the healthy tissues or organs. Most anticancer drugs are highly toxic; thus site-specific targeting would surely reduce their side effects. It is well known that the drug biodistribution and toxicity can be affected by many factors, including particle size and shape, types, functionalization techniques, particle administration methods and doses, among others [143]. Furthermore, nanocarriers can cause biodistribution and toxicity problems as they are immediately cleared from the blood by the reticuloendothelial system and can stay in organs for a long span of time.
Nonclinical Safety Evaluation of Advanced Therapies
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Timothy K. MacLachlan, Kendall S. Frazier, Mercedes Serabian
It should also be noted that the animal models used to evaluate biodistribution can sometimes be atypical in standard drug development. For example, the cotton rat is used to test adenoviruses, as this model is more permissive for viral replication. Additionally, tumor-bearing animal models are used because the presence of human tumor is needed to drive replication of the virus; otherwise, nontumor-bearing animals will clear the vector without an opportunity for replication. The background pathology of such models should be well understood before such models are employed to evaluate these endpoints.
Current status and advances in esophageal drug delivery technology: influence of physiological, pathophysiological and pharmaceutical factors
Published in Drug Delivery, 2023
Ai Wei Lim, Nicholas J. Talley, Marjorie M. Walker, Gert Storm, Susan Hua
Detailed safety and toxicology assessment is essential for clinical translation of any novel formulation (Hua et al., 2018). This is particularly important for pharmaceutical dosage forms containing components that have not yet been validated for safety in humans, as is often the case here with those designed for esophagus-related diseases. In addition to in vitro cellular studies, specialized toxicology studies in animal models need to be used to assess short-term and long-term toxicity. Biodistribution evaluation can also predict potential toxicological responses by determining factors such as off-target accumulation in healthy tissues as well as clearance mechanisms. Implementation of real-time imaging techniques (e.g. IVIS, MRI, CT) can allow improved understanding of the degree of interaction of esophageal targeting formulations with target and non-target organs and tissues after in vivo administration in longitudinal studies (Arms et al., 2018).
Revisiting techniques to evaluate drug permeation through skin
Published in Expert Opinion on Drug Delivery, 2021
Vamshi Krishna Rapalli, Arisha Mahmood, Tejashree Waghule, Srividya Gorantla, Sunil Kumar Dubey, Amit Alexander, Gautam Singhvi
Dermato-pharmacokinetic is the term coined for the determination of drug concentration continuously for a specific time interval [92]. The apparent advantage of using this study is the direct measurement of drug concentration at the site of action and the discernment of biodistribution and penetration mechanism of the drug [38]. When the drug is applied to the skin surface, it moves through various skin sections to reach its target site, eliciting a local or systemic therapeutic effect. Therefore, complete skin cannot be considered a single compartment, and it has to be separated into various constituent layers. This separation of skin layers is achieved by heat treatment at 60°C for 10 minutes [93], enzymatic digestion using trypsin [12], chemical treatment employing acetic acid, lime water, and ammonia [13], mechanical stretching [14], and suction [15]. The separation of skin layers is also achieved physically, i.e. using a dermatome. Dermatokinetic assessment of a topical formulation can be carried out by employing a tape stripping procedure, microdialysis technique, vasoconstrictor assay, and CRS. All these techniques have been sufficiently discussed in detail above.
99mTc radiolabeling of polyethylenimine capped carbon dots for tumor targeting: synthesis, characterization and biodistribution
Published in International Journal of Radiation Biology, 2021
Noha A. Bayoumi, Ahmed N. Emam
Biodistribution studies experiments were performed in accordance with the guidelines of the animal ethics committee of the Egyptian Atomic Energy Authority. Each mouse was injected intravenously (IV) in the tail vein with 200 µl samples containing 50 μg of 99mTc-citrate capped CDs or 99mTc-PEI capped CDs. The injected radioactivity was equivalent to 500 μCi per mouse. At different time intervals (0.5, 1, 2, 4 and 24 h post injection, n = 5 mice/time point) mice were weighed and sacrificed by neck dislocation. Different tissues and organs were dissected, washed twice with normal saline solution and weighed. Samples of fresh blood, bone and muscle were collected and weighed. Blood, bone and muscles were assumed to be 7, 10 and 40% of the total body weight, respectively (Darwish et al. 2018). The radioactivity of each organ or tissue sample was measured using shielded gamma scintillation counter. The uptake of the radiolabeled CDs in each organ was expressed as percent of the radioactivity per gram organ or body fluid (% Radioactivity/gram organ or body fluid) (Bayoumi et al. 2015). Target to non-target ratio (T/NT) has been calculated for each injected radiolabeled CDs. It represents the ratio between the radioactivity uptake of the tumor (target tissue) to the radioactivity uptake of the normal muscle (nontarget tissue). To understand the pharmacokinetic behavior of the prepared radiolabeled CDs, the radioactivity of the blood samples collected at different time points post injection was plotted against time and half-life (t1/2) was determined.