Preparation of ¹⁷⁷Lu‐labeled Nimotuzumab for radioimmunotherapy of EGFR‐positive cancers: Comparison of DOTA and CHX‐A″‐DTPA as bifunctional chelators

Abstract

177 Lu with Nimotuzumab on the radiochemical yields, purity, in vitro stability, and specificity of the radioimmunoconjugates to EGFR. Two immunoconjugates were prepared wherein Nimotuzumab was conjugated with the acyclic ligand p-NCS-Bn-CHX-A″-DTPA and macrocyclic ligand p-NCS-Bn-DOTA. These were radiolabeled with 177 Lu, purified on PD-10 column, and characterized by SE-HPLC. In vitro stability was determined up to 4 days post preparation.Specificity of the radioimmunoconjugates was ascertained by in vitro studies in A431 cells while the biodistribution patterns were studied in normal Swiss mice up to 96 hours post injection. Four to five molecules of CHX-A″-DTPA/ DOTA were attached to one molecule of Nimotuzumab. Radiochemical purity of both 177 Lu-CHX-A″-DTPA-Nimotuzumab and 177 Lu-DOTA-Nimotuzumab was determined to be greater than 98%. Both the radioimmunoconjugates exhibited good in vitro stability at 37°C up to 4 days post preparation in saline, and their clearance was largely by the hepatobiliary route. The DOTA-and CHX-A″-DTPA-based radioimmunoconjugates could be prepared with good radiochemical purity, in vitro stability, and specificity to EGFR. Further studies in EGFR-positive cancers would pave way for them for use in the clinics.

Preclinical Characterization of the 177Lu-Labeled Prostate Stem Cell Antigen (PSCA)-Specific Monoclonal Antibody 7F5

“…The data measured in PBS, cell media and human serum suggest a high stability of [ 177 Lu]Lu-CHX-A"-DTPA-7F5. These data are in line with other 177 Lu-labeled Abs conjugated with the CHX-A"-DTPA moiety [58,[60][61][62][63]. Moreover, we observed no enrichment in the skeleton during SPECT imaging.…”

Preparation and preliminary bioevaluation studies of 68Ga‐NOTA‐rituximab fragments as radioimmunoscintigraphic agents for non‐Hodgkin lymphoma

“…In this connection, preparation and bioevaluation of 177 Lu-labeled rituximab, Avastin, and nimotuzumab carried out in our laboratory have demonstrated their potential for radioimmunotherapy. 21,25,26 Previously, our group evaluated 99m Tc(CO) 3 -DTPA-rituximab as a SPECT imaging agent for NHL, wherein it showed slow pharmacokinetics and hepatobiliary clearance with accumulation in vital organs. 27 Camacho et al also made similar observations of slow pharmacokinetics and hepatic clearance with specific NHL imaging agent 99m Tc-Hynic-rituximab.…”

3D-Printed Drug-Loaded Composite Scaffolds to Promote Osteogenesis and Antibacterial Activity

“…Chlorhexidine (CHX) is a cationic biguanide anti-microbial agent with broad-spectrum antimicrobial activity, commonly used in dentistry, active against Gram-positive and Gram-negative bacteria. 22,23 CHX is absorbed directly onto the soft tissue surface of the oral cavity and is slowly released in the active form, significantly reducing the rate of surgical infections. 24,25,49 However, when CHX is applied directly to the site of infection, it is released abruptly.…”

“…Although the in vitro drug release and anti-infective ability of composite scaffolds have been investigated, , no systematic studies have been carried out to date regarding β-cyclodextrin (β-CD) encapsulated with antimicrobial agents onto PLA/nHA composite scaffolds. Chlorhexidine (CHX) is a cationic biguanide anti-microbial agent with broad-spectrum anti-microbial activity, commonly used in dentistry, active against Gram-positive and Gram-negative bacteria. , CHX is absorbed directly onto the soft tissue surface of the oral cavity and is slowly released in the active form, significantly reducing the rate of surgical infections. ,, However, when CHX is applied directly to the site of infection, it is released abruptly. In dentistry studies, β-CD has shown good sustained release properties as a carrier for the encapsulation of small molecules of CHX using the saturated ethanol solution method. , …”