A new enzyme-based molecular design can lower the retention of radioactive agents in the kidneys during radiotheranostic applications. This discovery could help to advance new and novel medical treatments.
Radiotheranostics is an approach that involves the use of a single radioactive agent for disease diagnosis and treatment. The advantage of radiotheranostics is with the convergence of diagnostic and therapeutic radiopharmaceuticals into a unified platform. As an example, in cancer treatment, radiotheranostic procedures typically involve the use of antibodies that bind to proteins abundantly found on the surface of cancerous cells.
These antibodies are labelled with a suitable radioisotope, which facilitates imaging procedures used to diagnose cancer and can be used to target cancerous cells and bombard them with deadly radiation as a form of treatment.
A concern with this medical process is that with the use of low-molecular-weight proteins and peptides, this can lead to unwanted accumulation of the associated radioactive metabolites in the kidneys. This is referred to as slow blood clearance, which causes bone marrow toxicities.
In addition, the accumulation and slow clearance of the radiolabeled particles (from the kidneys, also known as renal retention. The challenge of elevated radioactivity in the kidneys from the radiolabeled antibody fragments—detrimentally affecting both diagnosis precision and therapy outcomes—has hindered the progress of radiotheranostics applications for more than three decades.
In turn these phenomena interferes with diagnostic accuracy and may cause side effects. To tackle this, a study demonstrates that this limitation can be overcome by developing novel antibody fragments capable of enhancing overall treatment outcomes and imaging accuracy.
The research found that novel radioisotope-labelled antibody fragments facilitate the rapid elimination of the resulting radiometabolites from murine kidneys.
This breakthrough, from Chiba University, Japan, can contribute to personalized medical approaches with tremendous benefits to the treated patients.
According to lead researcher Dr. Hiroyuki Suzuki: “We have developed a radiolabeled antibody fragment that reduced renal radioactivity levels, where we used DOTA as the radiolabeling part. DOTA is a promising chelator, where a chelator is a molecule that forms a stable complex with a metal ion, such as a radiometal; this would find potential radiotheranostic applications.”
Dr. Suzuki’s team developed new radioiodinated antibody fragments with enzyme-cleavable linkages. After injecting the newly developed DOTA-based reagents into tumour-bearing mice, the team performed physiological imaging using single-photon emission computed tomography, which detects the gamma radiation emitted by the injected radiopharmaceuticals. Through such experiments, the research should accelerate the progress of radiotheranostics. The research appears in the Journal of Medicinal Chemistry, titled “Reduction of the Renal Radioactivity of 111In-DOTA-Labeled Antibody Fragments with a Linkage Cleaved by the Renal Brush Border Membrane Enzymes.”
