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

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 (⁵¹Cr) manufactured under Good Manufacturing Practices (GMP) has been challenging, and in 2024, the only remaining supplier ceased production. Now, only research-grade ⁵¹Cr is available, requiring risk control measures. Simultaneously, the Pyrophosphate (PYP) kits used to condition RBCs for technetium-99m (⁹⁹mTc) labeling are also no longer available. This report summarizes validations performed leading to reinfusions of blood cells labeled with a new kit for ⁹⁹mTc RBC labeling and research-grade ⁵¹Cr.

Three validations were conducted to confirm: (1) labeling efficiency of an alternative kit for ⁹⁹mTc labeling RBCs, (2) safety and labeling efficiency using research-grade ⁵¹Cr, 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.

Labeling efficiency of RBCs with ⁹⁹mTc 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 ⁵¹Cr, with labeling efficiency >98%.

We validated the use of research-grade ⁵¹Cr, an updated kit for ⁹⁹mTc labeling, and endotoxin testing for in vivo reinfusion of research-grade ⁵¹Cr labeled blood cells, and have infused >30 research participants with these changes under US FDA-approved protocols.