Development of Mn Labeled Trastuzumab for Extended Time Point PET Imaging of HER2.

Purpose: Due to their long circulation time in the blood, monoclonal antibodies (mAbs) such as trastuzumab, are usually radiolabeled with long-lived positron emitters for the development of agents for Positron Emission Tomography (PET) imaging. Manganese-52 (Mn, t = 5.6 d, β  = 29.

PET imaging of [52 Mn]Mn-DOTATATE and [52 Mn]Mn-DOTA-JR11.

Manganese-52 is gaining interest as an isotope for PET imaging due to its desirable decay and chemical properties for radiopharmaceutical development. Somatostatin receptor 2 (SSTR2) is significantly overexpressed by neuroendocrine tumors (NETs) and is an important target for nuclear imaging and therapy. As an agonist, [Ga]Ga-DOTATATE has demonstrated significant internalization upon interaction with receptor ligands, whereas [Ga]Ga-DOTA-JR11(as an antagonist) exhibits limited internalization but better pharmacokinetics and increased tumor uptake.

Improving the In Vivo Stability of [Mn]Mn(II) Complexes with 18-Membered Macrocyclic Chelators for PET Imaging.

We report the [Mn/Mn]Mn(II) complexes of the macrocyclic chelators PYAN [3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane] and CHXPYAN [(4,4,10,10)-3,5,9,11-tetraaza-1,7(2,6)-dipyridina-4,10(1,2)-dicyclohexanacyclododecaphane]. The X-ray crystal structures of Mn-PYAN and Mn-CHXPYAN evidence distorted octahedral geometries through coordination of the nitrogen atoms of the macrocycles. Cyclic voltammetry studies evidence reversible processes due to the Mn(II)/Mn(III) pair, indicating that the complexes are resistant to oxidation.

Chelation chemistry of manganese-52 for PET imaging applications.

Introduction: Due to its decay and chemical properties, interest in manganese-52 has increased for development of long-lived PET radiopharmaceuticals. Its long half-life of 5.6 days, low average positron energy (242 keV), and sufficient positron decay branching ratio make it suitable for radiolabeling macromolecules for investigating slow biological processes.

Direct Radiolabeling of Trastuzumab-Targeting Triblock Copolymer Vesicles with Zr for Positron Emission Tomography Imaging.

Radiolabeled drug nanocarriers that can be easily imaged positron emission tomography (PET) are highly significant as their outcome can be quantitatively PET-traced with high sensitivity. However, typical radiolabeling of most PET-guided theranostic vehicles utilizes modification with chelator ligands, which presents various challenges. In addition, unlike passive tumor targeting, specific targeting of drug delivery vehicles binding affinity to overexpressed cancer cell receptors is crucial to improve the theranostic delivery to tumors.

Natural and enriched Cr target development for production of Manganese-52.

Mn is a promising PET radiometal with a half-life of 5.6 days and an average positron energy of 242 keV. Typically, chromium of natural isotope abundance is used as a target material to produce this isotope through the Cr(p,n)Mn reaction.