α-Labeling of J591, an Antibody Targeting Prostate-Specific Membrane Antigen: The Technique and Considerations from the First Dedicated Production Lab at an Academic Institution in the United States

Steps for production assembly of ²²⁵Ac-J591. DG = durable grade; DTPA = diethylenetriaminepentaacetic acid; FDP = final drug product; HSA = human serum albumin; SDP = sterile drug product; SWFI = sterile water for injection; TMAA = triethylammonium acetate.

Labeling efficiency and radiochemical purity measured using instant thin-layer chromatography. (A) Labeling efficiency before ethylenediaminetetraacetic acid elusion, remarkable for high concentration of ²²⁵Ac bound to protein (green peak) and small percentage of unbound ²²⁵Ac, which has formed into daughter compounds of francium and bismuth (red peaks). (B and C) Radiochemical purity after ethylenediaminetetraacetic acid elusion at 2 h (B) and 24 h (C). Two hours after elusion, higher concentration of daughter compounds is noted whereas peak concentration of ²²⁵Ac bound to protein is stable. Because of shorter half-lives of daughter compounds, their presence is negligible at 24 h after elution, validating chemical purity of final product.

Schematic diagram of ²²⁵Ac decay and daughter compounds.

Endosafe-PTS test record. Endotoxin content should demonstrate limit well within guidelines of 175 endotoxin units for entire batch, as demonstrated here. Cal = calibration; CV = coefficient of variation; Rxn = reaction; Sec = seconds.