Principal methods for radioimmunotherapy. (A) Conventional directly-radiolabeled antibody. (B) Three-step pretargeted radioimmunotherapy (RIT) used by Pagel et al,⁴  comprising injection of streptavidin-antibody conjugate, followed by a clearing agent, and then administration of radiolabeled biotin. (C) Two-step bispecific, trivalent antibody (bsAb) pretargeted RIT (“affinity enhancement system”), whereby a bsAb is injected and binds to tumor with 2 of the 3 antibody arms. It is followed by injection of a radiolabeled hapten-peptide that binds to the third arm of the bsAb once the latter has cleared from the blood naturally.