Pharmacokinetics of protein and peptide conjugates

Abstract

Protein and peptide conjugates have become an important component of therapeutic and diagnostic medicine. These conjugates are primarily designed to improve pharmacokinetics (PK) of those therapeutic or imaging agents, which do not possess optimal disposition characteristics. In this review we have summarized preclinical and clinical PK of diverse protein and peptide conjugates, and have showcased how different conjugation approaches are used to obtain the desired PK. We have classified the conjugates into peptide conjugates, non-targeted protein conjugates, and targeted protein conjugates, and have highlighted diagnostic and therapeutic applications of these conjugates. In general, peptide conjugates demonstrate very short half-life and rapid renal elimination, and they are mainly designed to achieve high contrast ratio for imaging agents or to deliver therapeutic agents at sites not reachable by bulky or non-targeted proteins. Conjugates made from non-targeted proteins like albumin are designed to increase the half-life of rapidly eliminating therapeutic or imaging agents, and improve their delivery to tissues like solid tumors and inflamed joints. Targeted protein conjugates are mainly developed from antibodies, antibody derivatives, or endogenous proteins, and they are designed to improve the contrast ratio of imaging agents or therapeutic index of therapeutic agents, by enhancing their delivery to the site-of-action.

Comparison of Quantification of Target-Specific Accumulation of [18F]F-siPSMA-14 in the HET-CAM Model and in Mice Using PET/MRI

“…In the mouse model, the accumulation of [ 18 F]F-siPSMA-14 in the renal cortex was clearly demonstrated visually. In general, the excretion of small molecules and peptides occurs via the kidneys [76,77]. While in the mouse, excretion occurs via the urinary bladder, in the closed system chick embryo, excretions are accumulated in the allantoic fluid [78].…”

Multivalent Probes in Molecular Imaging: Reality or Future?

“…PEG-based linkers are one of the first choices because PEG copolymers are water-soluble, neutrally charged, and biocompatible, and have properties that shield them from degradation and excretion [62]. However, PEGylation also favors nonspecific binding of MMIAs, which lowers the remaining fraction of MMIAs that can target the diseased tissue [67].…”

An 111In-labelled bis-ruthenium(ii) dipyridophenazine theranostic complex: mismatch DNA binding and selective radiotoxicity towards MMR-deficient cancer cells

“…One attractive option is bioconjugation employing a cleavable linker to a peptide or antibody that targets surface receptors overexpressed by cancers. 67 Peptide conjugation can substantially improve biodistribution and pharmacokinetics of an administered agent 68 and numerous design strategies for metallo-drug peptide conjugation have been outlined in a recent review. 69 Finally, 111 In radiopharmaceuticals are also compatible with drug-delivery approaches such as liposome-encapsulation of the chelator before subsequent radiometal loading.…”