Same-Day Imaging Using Small Proteins: Clinical Experience and Translational Prospects in Oncology

Abstract

Imaging of expression of therapeutic targets may enable stratification of patients for targeted treatments. The use of small radiolabeled probes based on the heavy-chain variable region of heavy-chain-only immunoglobulins or nonimmunoglobulin scaffolds permits rapid localization of radiotracers in tumors and rapid clearance from normal tissues. This makes high-contrast imaging possible on the day of injection. This mini review focuses on small proteins for radionuclide-based imaging that would allow same-day imaging, with the emphasis on clinical applications and promising preclinical developments within the field of oncology.

Benefit of Later-Time-Point PET Imaging of HER3 Expression Using Optimized Radiocobalt-Labeled Affibody Molecules

“…By randomization of these amino acids, affibody molecules have been designed against a number of different targets (e.g., EGFR, HER2, IGF1-R) [17,18]. The smaller size of affibody molecules (7-8 kDa) and their fast pharmacokinetics increases extravasation and tumor penetration, reduces enhanced permeability and retention (EPR) effects and might, therefore, improve imaging contrast compared to antibodies and their derivatives [17][18][19]. Typically, a high contrast is obtained on the same day as the injection, as early as three to four hours post-injection (pi).…”

The Future of Nuclear Medicine as an Independent Specialty

“…Their utility depends on their ability to answer various clinical questions, as highlighted in Table 1. Imaging biomarkers include small molecules, peptides and peptidomimetics, and antibodies and antibody fragments (18)(19)(20)(21). Small molecules-metabolic and cell surface receptor-targeted probes-can successfully improve the management and outcome of patients affected by neurodegenerative (22), cardiovascular (23), inflammatory and infectious diseases (24), and cancer (4,5).…”

“…Established Imaging Biomarkers 18 F-FDG PET/CT imaging is a key imaging modality in cancer, and its use is still increasing. It remains the most successfully translated molecular imaging platform, a hybrid imaging tool for precision medicine.…”

“…More than 5 million studies are performed worldwide each year. 18 F-FDG serves as a diagnostic and prognostic biomarker from early-to late-stage cancer. Its use as an intermediate endpoint biomarker for early therapy response assessments has changed the practice of oncology.…”

Recombinant expression of nanobodies and nanobody-derived immunoreagents

“…With respect to conventional IgGs (150 kDa), the tiny dimension of nanobody confers the exclusive capacity to bind to cryptic epitopes of viruses [2], a characteristic that at the present could be particularly useful to produce reagents suitable for coronavirus studies. Over the years, it emerged that VHHs are effective crystallography chaperones and molecular tools for protein structural characterization [3][4][5], convenient carriers for radioisotopes with extremely short half-life to use for in vivo PET/ SPECT imaging [6][7][8][9][10], valid immunoreagents for the controlled and oriented functionalization of nanoparticles, nanogels and biosensors [11][12][13][14] and that they can be even internalized by mammalian cells when provided with a suitable leader peptide [15]. More recently, their minimal dimension has been particularly appreciated by scientists looking for binders suitable to optimize the performance of super resolution microscopy [16][17][18] and to create tandem chimeric antigen receptors (CARs) that show higher target specificity due to the possibility of binding simultaneously multiple antigens [19].…”