{"entity":{"id":"albumin-binder-ligands","kind":"technology","name":"Albumin-binder ligands","aka":["albumin-binding moiety","Evans blue conjugate","IPBA conjugate"],"tldr":"Attaching a small chemical 'hook' that grips the body's own albumin protein makes a radioactive drug stay in the bloodstream for longer, so more of it reaches the tumour before it is cleared out through the kidneys.","summary":"Small-molecule and peptide radioligands (such as PSMA-617) are cleared from the blood within minutes to a few hours, which limits the fraction of injected activity that can diffuse into and bind tumour tissue before excretion. Conjugating an albumin-binding moiety, most commonly a truncated Evans blue (EB) dye derivative or 4-(p-iodophenyl)butyric acid (IPBA/IP), to the targeting ligand allows reversible, non-covalent binding to circulating serum albumin (biological half-life around 19 days), which extends the ligand's effective blood half-life from minutes to several hours without permanently trapping the radionuclide.\n\nIn preclinical work, Evans-blue-modified PSMA-617 (EB-PSMA-617) showed markedly extended blood retention compared with unmodified PSMA-617 and produced higher tumour uptake and greater therapeutic efficacy at lower administered activity in mouse models; a single low dose eliminated PSMA-positive tumours in one widely cited study. Albumin-binder chemistry generalises across chelator and radionuclide (86Y/90Y/177Lu-DOTA-EB-PSMA-617; 64Cu-PSMA-CM using an MPA albumin-binding moiety) and across targets (SSTR, GRPR ligands). The main design trade-off is pharmacokinetic: too strong an albumin interaction raises blood and normal-organ (especially bone marrow) dose and can worsen the therapeutic index, so linker length, albumin-binding affinity and total charge are tuned empirically for each ligand; increased kidney or hepatobiliary retention has also been reported for some albumin-binder designs and must be balanced against the gain in tumour dose.","asOf":"2026-09-22","links":[{"label":"Wang et al.: Single low-dose injection of Evans blue modified PSMA-617 radioligand therapy (Bioconjugate Chem 2018)","url":"https://pubs.acs.org/doi/abs/10.1021/acs.bioconjchem.8b00556"},{"label":"Albumin-binding PSMA ligands: implications for expanding the therapeutic window (J Nucl Med 2019)","url":"https://jnm.snmjournals.org/content/60/5/656"},{"label":"Development of an albumin-based PSMA probe with prolonged circulation, PMC 2020","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7773938/"}],"tags":["chemistry","pharmacokinetics","PSMA"],"related":["dota-chelation","radioligand-therapy","psma","cu-64","y-86","lu-177","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["dota-chelation"],"notes":[],"principle":"A small chemical moiety with affinity for serum albumin (such as a truncated Evans blue dye or 4-(p-iodophenyl)butyric acid) is attached to the radioligand; it binds albumin reversibly, piggy-backing on the protein's long circulating half-life so the ligand stays in the bloodstream, and therefore available to bind the tumour, for hours instead of minutes.","strengths":[],"limitations":[],"since":"First albumin-binder radioligand conjugates reported around 2010; PSMA-EB conjugates from 2018"},"route":"/technologies/albumin-binder-ligands/","neighbours":{"technology":[{"id":"dota-chelation","kind":"technology","name":"DOTA chelation","route":"/technologies/dota-chelation/"},{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","route":"/technologies/radioligand-therapy/"}],"target":[{"id":"psma","kind":"target","name":"PSMA","route":"/targets/psma/"}],"isotope":[{"id":"cu-64","kind":"isotope","name":"Copper-64","route":"/isotopes/cu-64/"},{"id":"lu-177","kind":"isotope","name":"Lutetium-177","route":"/isotopes/lu-177/"},{"id":"y-86","kind":"isotope","name":"Yttrium-86","route":"/isotopes/y-86/"},{"id":"y-90","kind":"isotope","name":"Yttrium-90","route":"/isotopes/y-90/"}]}}