Imaging using radiolabelled targeted proteins: radioimmunodetection and beyond

Abstract

The use of radiolabelled antibodies was proposed in 1970s for staging of malignant tumours. Intensive research established chemistry for radiolabelling of proteins and understanding of factors determining biodistribution and targeting properties. The use of radioimmunodetection for staging of cancer was not established as common practice due to approval and widespread use of [ 18 F]-FDG, which provided a more general diagnostic use than antibodies or their fragments. Expanded application of antibody-based therapeutics renewed the interest in radiolabelled antibodies. RadioimmunoPET emerged as a powerful tool for evaluation of pharmacokinetics of and target engagement by biotherapeutics. In addition to monoclonal antibodies, new radiolabelled engineered proteins have recently appeared, offering highcontrast imaging of expression of therapeutic molecular targets in tumours shortly after injection. This creates preconditions for noninvasive determination of a target expression level and stratification of patients for targeted therapies. Radiolabelled proteins hold great promise to play an important role in development and implementation of personalised targeted treatment of malignant tumours. This article provides an overview of biodistribution and tumour-seeking features of major classes of targeting proteins currently utilized for molecular imaging. Such information might be useful for researchers entering the field of the protein-based radionuclide molecular imaging.

The Use of a Non-Conventional Long-Lived Gallium Radioisotope 66Ga Improves Imaging Contrast of EGFR Expression in Malignant Tumours Using DFO-ZEGFR:2377 Affibody Molecule

“…The use of small scaffold proteins, such as affibody molecules, offers an advantage in radionuclide molecular imaging compared with the use of monoclonal antibodies due to the potential for affibody molecules to provide higher contrast [ 45 ]. Consequently, the sensitivity of such imaging is also higher.…”

Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1

“…The difference in the renal uptake of [ 125 I]I-PIB-Ec1 and [ 99m Tc]Tc(CO) 3 -Ec1 was spectacular already at 6 h after injection. A high re-absorption in the proximal tubuli of the kidneys is a common feature of imaging probes based on short peptides [ 49 ] and ESPs, such as affibody molecules, ADAPTs, or DARPins [ 20 , 50 , 51 ]. In the case of short peptides, the re-absorption could be suppressed by blocking scavenger receptors with cationic amino acids or succinylated bovine gelatin (Gelofusine) [ 49 ].…”

Preclinical Evaluation of 99mTc-ZHER2:41071, a Second-Generation Affibody-Based HER2-Visualizing Imaging Probe with a Low Renal Uptake

“…Still, imaging probes based on therapeutic antibodies clear slowly from blood. This causes a low imaging contrast (even 4–5 days after injection) and an elevated dose burden [ 11 ]. The use of small imaging probes, which are based on the VHH domain or engineered scaffold proteins, enables to reduce the optimal imaging time to a few hours after injection and to increase the contrast of imaging, which enhances sensitivity [ 12 ].…”

“…PET studies using the DOTA-conjugated 68 Ga-labelled second-generation affibody molecule ABY-025 have demonstrated excellent sensitivity and specificity in detecting HER2 expressing metastases in patients with breast cancer [ 20 ]. Importantly, a typical clinical investigation using this tracer would give an effective dose in the range of 5–6 mSv [ 21 ], which is appreciably lower compared with doses typical for immunoPET (14–22 mSv) [ 11 ]. Still, PET imaging is relatively available in Northern America and Western Europe.…”