Janevik-Ivanovska, Emilija (2018) Therapeutic Radiopharmaceuticals – Importance of Preclinical Investigation for Effective Clinical Application. In: 18th Biennial Congress of the South African Society of Nuclear Medicine (SASNM), 10-12 Aug 2018, Pretoria, South Africa.
Preview |
Text
WorldJNuclMed18181-5761528_160015.pdf Download (646kB) | Preview |
Preview |
Text
SASNM PRETORIA 2018 E.Janevik .pdf Download (69MB) | Preview |
Abstract
Within the last decade, there has been an increasing interest in developing new radiopharmaceuticals for therapy, especially targeted radionuclide therapy (RNT) with labelled monoclonal antibodies (mAbs) and peptides as a complementary modality for the treatment of certain cancers.
Intact antibodies and their truncated counterparts (eg, Fab, scFv fragments) are generally exquisitely specific and selective vectors, enabling recognition of individual cancer-associated molecular phenotypes against a complex and dynamic biomolecular background. Complementary alignment of these advantages with unique properties of radionuclides is a defining paradigm in both radioimmunoimaging and radioimmunotherapy, which remain some of the most adept and promising tools for cancer diagnosis and treatment.
How many potential radiopfarmaceuticals and how many can be apropriate for for therapy is the crucial approach, especialy if we can considered that only less than 5% of in vitro targets allow development of an in vivo probe as potential radiopfarmaceutical for therapy. The most important criteras before to start preclinical investigation, as the first and the most important step of introduction and treat one radiopharmaceutical as potential for therapy are:
• High target activity and concentration including affinity and specificity, absence of biological barriers (i. e. endothelium, blood brain barrier,...) and stable labeling of compound
• Low background activity, that comprehend non- specific accumulation, circulating or interstitial activity and renal or hepatic elimination
• Signal amplification as cell trapping, enzymatic conversion and “Reporter” radioactive molecules. Preclinical studies for therapeutic radiopharmaceuticals
should be designed to assess:
• The in vivo stability of the radionuclide complex • The animal biodistribution of the radionuclide • The potential chemical toxicity
• The radiation exposure of tissues.
Data required to establish preclinical safety of radiopharmaceuticals include
• In vitro target/receptor profiling including
pharmacodynamics
• Pharmacokinetics
• Potential chemical toxicity including antigenicity
• Radiation exposure of tissues
• Late radiation toxicity
• The dose evoking pharmacologic activity or
antigenicity, and
• The minimum radioactivity dose needed for
satisfactory imaging.
For therapeutic radiopharmaceuticals, safety is determined by the margin between-the dose exceeding organ tolerance or inducing late radiation toxicity, and- the minimum efficacious dose.
The goal of this paper is to discuss how translational potency can be maximized through rational selection of antibody-nuclide couples for therapy in preclinical models, using our experience introducing ready to use kit formulation of freeze dries conjugated and potentially to give some idea how to come back to the radioimmunoimaging using the new potential PET radionuclide.
Item Type: | Conference or Workshop Item (Lecture) |
---|---|
Subjects: | Medical and Health Sciences > Clinical medicine Medical and Health Sciences > Health biotechnology Medical and Health Sciences > Other medical sciences |
Divisions: | Faculty of Medical Science |
Depositing User: | Emilija Janevik |
Date Deposited: | 06 Feb 2019 08:01 |
Last Modified: | 06 Jun 2019 08:00 |
URI: | https://eprints.ugd.edu.mk/id/eprint/21468 |
Actions (login required)
![]() |
View Item |