Use of research‐grade radioisotopes for in‐human recovery and survival studies

Abstract Background and Objectives Red blood cells ( RBCs ) and platelets are evaluated for in vivo quality using recovery and survival measurements in healthy volunteers. Radiolabeling is the standard method for tracking blood cells post‐transfusion. The supply of chromium‐51 ( 51 Cr) manufactured under Good Manufacturing Practices ( GMP ) has been challenging, and in 2024, the only remaining supplier ceased production. Now, only research‐grade 51 Cr is available, requiring risk control measures. Simultaneously, the Pyrophosphate ( PYP ) kits used to condition RBCs for technetium‐99m ( 99 mTc) labeling are also no longer available. This report summarizes validations performed leading to reinfusions of blood cells labeled with a new kit for 99 mTc RBC labeling and research‐grade 51 Cr . Materials and Methods Three validations were conducted to confirm: (1) labeling efficiency of an alternative kit for 99 mTc labeling RBCs, (2) safety and labeling efficiency using research‐grade 51 Cr, and (3) the ability of the Pyrosate®‐Rapid Endotoxin Detection (PRED) kit to detect pyrogens in research‐grade material and in end‐products for in vivo use. Results Labeling efficiency of RBCs with 99 mTc using the Ultratag™ RBC kit was >98% and demonstrated consistency in labeling across different sample preparation conditions. Filtration of the radioisotope stock and endotoxin testing of the infusate served as effective risk mitigation steps, supporting safe use of research‐grade 51 Cr, with labeling efficiency >98%. Conclusions We validated the use of research‐grade 51 Cr, an updated kit for 99 mTc labeling, and endotoxin testing for in vivo reinfusion of research‐grade 51 Cr labeled blood cells, and have infused >30 research participants with these changes under US FDA–approved protocols.