Intravenous, Intraperitoneal, and Subcutaneous Routes of Administering ⁶⁴Cu-DOTA-HB22.7 Display Equivalent Tumor Targeting Ability.

BACKGROUND: Chemotherapy for Non-Hodgkin’s Lymphoma (NHL) is initially effective, but often limited by toxicity and resistance. New agents for the treatment of NHL are needed. HB22.7 is a monoclonal antibody that binds CD22 and has previously been shown to reduce human lymphoma xenograft volume in nude mice.

OBJECTIVES: (1) Develop a ⁶⁴Cu-DOTA-HB22.7 antibody, for in vivo imaging and potential therapy of NHL. (2) Determine if tumor targeting of ⁶⁴Cu-DOTA-HB22.7 is equivalent between intravenous (IV), intraperitoneal (IP), and subcutaneous (SQ) routes of administration.

METHODS: DOTA-HB22.7’s ability to bind CD22+ cells was assessed by flow cytometry. ⁶⁴Cu-DOTA-HB22.7 was injected IV, IP, or SQ into xenograft-bearing nude mice and tumor targeting assessed by positron emission tomography (PET) and biodistribution assay. Pharmacokinetics were determined by measuring radioactivity of blood samples. Serum was analyzed by radio-TLC.

RESULTS: DOTA conjugation does not affect HB22.7’s ability to bind CD22. ⁶⁴Cu-DOTA-HB22.7 demonstrates specific tumor targeting at 24 and 48 hrs. Targeting is equivalent regardless of route of administration. Pharmacokinetics demonstrate that ⁶⁴Cu-DOTA-HB22.7 can access the bloodstream (and thus, target tumor) in IP or SQ injections. By 48 hrs, blood ⁶⁴Cu levels are (a) equivalent, regardless of injection route and (b) below peak levels, indicating clearance from the circulation. Serum analysis shows that right-shifted TLC peaks, possibly ⁶⁴Cu-DOTA-HB22.7 metabolites, are present only in the IV injected group at 48 hrs.

CONCLUSION: These findings establish ⁶⁴Cu-DOTA-HB22.7 as an NHL-specific imaging agent and indicate its potential for use in radioimmunotherapy. These findings provide evidence that more accessible routes of administration can achieve equivalent targeting results, and may lead to more efficient and accurate administration of antibody-based therapeutics in mice.