Preclinical evaluation of Manganese-52 labelled cyclodextrin: a prostaglandin E2 affine imaging probe

• Labelling with 52 Mn makes it possible to specify the biokinetics of cyclodextrins. • 52 Mn seems promising to establish PET radiopharmaceuticals. • [ 52 Mn]Mn-DOTAGA-RAMEB has the potential to identify PGE2 expressing malignancies. Prostaglandin E2 (PGE2) is implicated in several tumor-related biological processes, making it a promising biomarker for molecular imaging. In nuclear medicine, radiolabelled cyclodextrins have emerged as potential probes to target PGE2 in various cancer types. Hereafter, we aimed to specify the pharmacokinetics of a novel Manganese-52-labelled randomly methylated β-cyclodextrin ([ 52 Mn]Mn-DOTAGA-RAMEB) by performing multiple time-point positron emission tomography and ex vivo biodistribution studies in PGE2 positive BxPC-3 pancreatic adenocarcinoma xenografts. In line with the ex vivo findings, [ 52 Mn]Mn-DOTAGA-RAMEB showed early and specific tumor uptake (30 and 60 min after injection), followed by rapid wash-out and renal clearance. Our experimental data demonstrate the feasibility of 52 Mn-labelled RAMEB cyclodextrin to identify PGE2 expressing tumors, although further pharmacokinetic optimization is required to enhance tumor retention and fully exploit its diagnostic potential.