Biologics are emerging as the most important class of drugs and are used to treat a large variety of pathologies. Most of biologics are proteins administered in large amounts, either by intramuscular injection or by intravenous infusion. Asparaginase is a large tetrameric protein assembly, currently used against acute lymphoblastic leukemia. Here, a gadolinium(III)-DOTA derivative has been conjugated to asparaginase, and its relaxation properties have been investigated to assess its efficiency as a possible theranostic agent. The field-dependent 1 H longitudinal relaxation measurements of water solutions of gadolinium(III)-labeled asparaginase indicate a very large increase in the relaxivity of this paramagnetic protein complex with respect to small gadolinium chelates, opening up the possibility of its use as an MRI contrast agent.

Diagnostic medical imaging utilizes magnetic resonance (MR) to provide anatomical, functional, and molecular information in a single scan. Nanoparticles are often labeled with Gd(III) complexes to amplify the MR signal of contrast agents (CAs) with large payloads and high proton relaxation efficiencies (relaxivity, r 1). This study examined the MR performance of two structurally unique cages, AaLS-13 and OP, labeled with Gd(III). The cages have characteristics relevant for the development of theranostic platforms, including (i) well-defined structure, symmetry, and size; (ii) the amenability to extensive engineering; (iii) the adjustable loading of therapeutically relevant cargo molecules; (iv) high physical stability; and (v) facile manufacturing by microbial fermentation. The resulting conjugates showed significantly enhanced proton relaxivity (r 1 = 11–18 mM–1 s–1 at 1.4 T) compared to the Gd(III) complex alone (r 1 = 4 mM–1 s–1). Serum phantom images revealed 107% and 57% contrast enhancements for Gd(III)-labeled AaLS-13 and OP cages, respectively. Moreover, proton nuclear magnetic relaxation dispersion (1H NMRD) profiles showed maximum relaxivity values of 50 mM–1 s–1. Best-fit analyses of the 1H NMRD profiles attributed the high relaxivity of the Gd(III)-labeled cages to the slow molecular tumbling of the conjugates and restricted local motion of the conjugated Gd(III) complex.

Proteins JOYNLABSeveral fruit juices are used as oral contrast agents to improve the quality of images in magnetic resonance cholangiopancreatography. They are often preferred to conventional synthetic contrast agents because of their very low cost, natural origin, intrinsic safety, and comparable image qualities. Pineapple and blueberry juices are the most employed in clinical practice due to their higher content of manganese(II) ions. The interest of pharmaceutical companies in these products is testified by the appearance in the market of fruit juice derivatives with improved contrast efficacy.Here, we investigate the origin of the contrast of blueberry juice, analyze the parameters that can effect it, and elucidate the differences with pineapple juice and manganese(II) solutions. It appears that, although manganese(II) is the paramagnetic ion responsible for the contrast, it is the interaction of manganese(II) with other juice components that modulates the efficiency of the juice as a magnetic resonance contrast agent. On these grounds, we conclude that blueberry juice concentrated to the same manganese concentration of pineapple juice would prove a more efficient contrast agent than pineapple juice.