IL-12 is an attractive target for imaging active antitumor immunity, inflammation, and infection due to its function in innate and adaptive immune signaling. It has been widely reported to be involved in cancer initiation and progression, autoimmunity, as well as graft vs host disease. Here, we report the development and preclinical evaluation of an IL-12-specific positron emission tomography (PET) tracer. Biodistribution of tracer was evaluated in BALB/c mice, using lipopolysaccharide (LPS) administered intramuscularly to mimic infection and stimulate IL-12 production (40µg LPS in 50µL PBS). One hour post administration each participant received intraveinous administration of [89Zr]- αIL12 tracer, and PET images were taken 5, 24, 48, and 72 hours post injection (hpi). Representative planar images show significantly higher uptake in LPS-treated mice as compared to controls. In a separate cohort of LPS-treated BALB/c mice, all tissues identified as significantly different via tracer were collected and evaluated via qPCR to verify IL-12 transcription in each tissue. To evaluate the utility of [89Zr]- αIL12 as a metric of cancer immunotherapy response where antigen presenting cells are activated, we tested intratumoral delivery of Adv/GM-CSF, which we has been shown to promote anti-tumor immunity. BALB/c mice were seeded orthotopically with TUBO (murine mammary carcinoma) in the mammary fat pad. Once TUBO tumors reached a volume of ~50 mm3, mice were divided into treated and untreated groups. Treated mice received three intratumoral injections of 108 PFU Adv/GM-CSF, once every two days, while control mice received vehicle control. On the day of the last dose, each subject received tracer injection and 72 hours later all mice were imaged via PET. Representative planar images demonstrate high uptake of [89Zr]- αIL12 in treated vs. untreated mice. Targeting of soluble cytokines such as IL-12 by PET imaging may serve as a noninvasive way to evaluate the function of the immune milieu in situ.
Citation Format: James E. Glassbrook, Joshua Mandella, Nerissa T. Viola-Villegas, Heather M. Gibson. Evaluation of an immunoPET tracer for IL-12 in a preclinical model of inflammatory immune responses [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P055.