111In-Ibritumomab tiuxetan, commercially known as 111In-Zevalin, was developed by IDEC Pharmaceuticals as a diagnostic imaging agent to facilitate the selection of patients suitable for treatment with 90Y-Ibritumomab tiuxetan, commonly referred to as Zevalin. Given that 90Y, or Yttrium-90, is a pure beta-emitter and lacks gamma rays, it is not inherently suitable for imaging purposes. This limitation necessitated the development of a companion imaging agent that could reliably map the distribution of the therapeutic antibody in the body. 111In, or Indium-111, was chosen as the optimal radionuclide for this purpose because its chemical properties were highly compatible with those of 90Y, allowing for an accurate simulation of Zevalin’s biodistribution and behavior in the patient.
Upon completion of its development, 111In-Ibritumomab tiuxetan was submitted for regulatory approval alongside Zevalin, and both received marketing authorization simultaneously. For several years, the use of 111In-Ibritumomab tiuxetan was a mandatory initial step in the Zevalin therapeutic regimen. It served as a crucial diagnostic tool to predict which patients were most likely to respond positively to Zevalin treatment, thereby aiding in the stratification and selection of patients.
However, as clinical experience with Zevalin grew, it became apparent that even patients who did not demonstrate a positive response to 111In-Ibritumomab tiuxetan imaging could still benefit from Zevalin therapy. This finding gradually led to a reevaluation of the necessity of pre-treatment imaging with 111In-Ibritumomab tiuxetan. Over time, clinical studies and real-world data confirmed that the stratification of patients based on this imaging technique was no longer relevant. As a result, regulatory agencies across various regions began to revise their guidelines, eventually approving the use of Zevalin without the prerequisite of prior imaging with 111In-Ibritumomab tiuxetan.
In the United States, this revised protocol received approval in 2011, allowing for a more streamlined treatment process. Furthermore, while 111In-Ibritumomab tiuxetan could theoretically have been employed for post-treatment follow-up as well, advancements in imaging technology have provided more effective alternatives. Today, positron emission tomography/computed tomography (PET/CT) scans, often coupled with the use of fluorodeoxyglucose (FDG), are considered more efficient and accurate for monitoring patients after Zevalin therapy.