Renesmee Kuo

All Publications

• Advancing In Vivo Detection of T-Cell Function: Development and Preclinical Evaluation of 89Zr-Ivuxolimab, a Human OX40 PET Tracer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Kalita, M., Kuo, R. C., Reyes, S. T., Colburg, D. R., Falk, I. N., Anders, D., Vermesh, O., Hayee, S., Azevedo, E. C., Nagy, S. C., Deal, E. M., Chen, A. A., Kong, C. S., Simonetta, F., Giddabasappa, A., Keliher, E. J., Bartlett, D. W., Maresca, K. P., James, M. L., Alam, I. S. 2025

  Abstract

  The variable response to cancer immunotherapies highlights a critical gap in our ability to predict and monitor treatment efficacy. To address this, there is an urgent clinical need for advanced molecular imaging technologies that can noninvasively and precisely assess whole-body immune responses. The OX40 receptor (CD134), a potent costimulatory molecule on T cells, serves as a highly specific marker of T-cell activation, an early and crucial event in immunotherapy efficacy. In this study, we report the development of a human OX40-specific radiotracer based on a clinically evaluated therapeutic-ivuxolimab-and assess its utility for PET imaging of activated T cells in vivo. Methods: Deferoxamine conjugation and 89Zr radiolabeling were optimized for ivuxolimab. In vitro specificity of the resultant tracer, 89Zr-ivuxolimab, was then assessed using primary human T cells and stably transfected human OX40+ (huOX40+) human embryonic kidney 293 (HEK293) cells. In vivo specificity and biodistribution of 89Zr-ivuxolimab were confirmed in subcutaneously implanted huOX40+ HEK293 or parental HEK293 tumor-bearing mice. To evaluate 89Zr-ivuxolimab's utility for detecting T-cell activation in vivo, we used a transgenic human OX40 murine model of acute graft-versus-host disease. Ex vivo gamma counting, autoradiography, and immunohistochemistry were performed to verify tracer-binding specificity. Results: 89Zr-ivuxolimab was reproducibly synthesized and showed significantly increased in vitro binding to activated human T cells versus resting cells (P < 0.0001) and increased binding to huOX40+ HEK293 cells versus HEK293 cells (P < 0.0001). Longitudinal PET/CT imaging of tumor-bearing mice over 5 d revealed markedly higher tracer accumulation in huOX40+ HEK293 tumors compared with HEK293 tumors (P < 0.0001). 89Zr-ivuxolimab successfully detected T-cell activation in the spleen, mesenteric lymph node, and gastrointestinal tract of mice with graft-versus-host disease induced by transgenic murine T cells expressing human OX40, compared with control groups (total body irradiation, P < 0.0001; bone marrow, P < 0.001). Ex vivo gamma counting of tissues, autoradiography, and immunohistochemistry corroborated PET findings and confirmed tracer specificity for OX40. Conclusion: 89Zr-ivuxolimab is a promising radiotracer for clinical translation as an imaging agent for activated T cells. Further investigation of its ability to monitor and predict response to different cancer immunotherapy modalities is warranted.

  View details for DOI 10.2967/jnumed.125.269799

  View details for PubMedID 40707142

• Revealing the suppressors: A new PET imaging approach for detecting MDSCs before and after immunotherapy in a model of brain metastases Kuo, R., Verma, R., Reyes, S., Nagy, S., Kalita, M., D'moore, D., Ehsani, A., Pisani, L., Alam, I., Milligan, G., Lim, M., James, M. SOC NUCLEAR MEDICINE INC. 2025

  View details for Web of Science ID 001545700600023

• Early detection and tracking of activated macrophages and microglia in a mouse model of multiple sclerosis using [18F]OP-801 PET imaging before and after a novel immunomodulatory drug Kuo, R., Carlson, M., Malik, N., Reyes, S., Nagy, S., Kalita, M., Alam, I., Jackson, I., Beinat, C., Acosta, C., Falk, I., Azevedo, C., Avci, N., Minami, S., Cleland, J., James, M. SOC NUCLEAR MEDICINE INC. 2024

  View details for Web of Science ID 001289165603246

• Illuminating pro-inflammatory myeloid cells in a murine model of multiple sclerosis using a new 18F-labeled GPR84-targeted radiotracer Reyes, S., Kalita, M., Kuo, R., Straniero, V., Marsango, S., Pandrala, M., Malik, N., Jain, P., Suigo, L., Nagy, S., Wu, T., Valoti, E., Milligan, G., James, M. SOC NUCLEAR MEDICINE INC. 2024

  View details for Web of Science ID 001289165603162

• Development and comparison of two novel PET tracers for imaging proinflammatory receptor GPR84 in human cells and tissues Nagy, S., Kalita, M., Jackson, I., Reyes, S., Kuo, R., Malik, N., Pandrala, M., Zhang, B., Marsango, S., Straniero, V., Suigo, L., Valoti, E., Alam, I., Milligan, G., James, M. SOC NUCLEAR MEDICINE INC. 2024

  View details for Web of Science ID 001289165602056

• PET Imaging of Innate Immune Activation Using 11C Radiotracers Targeting GPR84. JACS Au Kalita, M., Park, J. H., Kuo, R. C., Hayee, S., Marsango, S., Straniero, V., Alam, I. S., Rivera-Rodriguez, A., Pandrala, M., Carlson, M. L., Reyes, S. T., Jackson, I. M., Suigo, L., Luo, A., Nagy, S. C., Valoti, E., Milligan, G., Habte, F., Shen, B., James, M. L. 2023; 3 (12): 3297-3310

  Abstract

  Chronic innate immune activation is a key hallmark of many neurological diseases and is known to result in the upregulation of GPR84 in myeloid cells (macrophages, microglia, and monocytes). As such, GPR84 can potentially serve as a sensor of proinflammatory innate immune responses. To assess the utility of GPR84 as an imaging biomarker, we synthesized 11C-MGX-10S and 11C-MGX-11Svia carbon-11 alkylation for use as positron emission tomography (PET) tracers targeting this receptor. In vitro experiments demonstrated significantly higher binding of both radiotracers to hGPR84-HEK293 cells than that of parental control HEK293 cells. Co-incubation with the GPR84 antagonist GLPG1205 reduced the binding of both radiotracers by >90%, demonstrating their high specificity for GPR84 in vitro. In vivo assessment of each radiotracer via PET imaging of healthy mice illustrated the superior brain uptake and pharmacokinetics of 11C-MGX-10S compared to 11C-MGX-11S. Subsequent use of 11C-MGX-10S to image a well-established mouse model of systemic and neuro-inflammation revealed a high PET signal in affected tissues, including the brain, liver, lung, and spleen. In vivo specificity of 11C-MGX-10S for GPR84 was confirmed by the administration of GLPG1205 followed by radiotracer injection. When compared with 11C-DPA-713-an existing radiotracer used to image innate immune activation in clinical research studies-11C-MGX-10S has multiple advantages, including its higher binding signal in inflamed tissues in the CNS and periphery and low background signal in healthy saline-treated subjects. The pronounced uptake of 11C-MGX-10S during inflammation, its high specificity for GPR84, and suitable pharmacokinetics strongly support further investigation of 11C-MGX-10S for imaging GPR84-positive myeloid cells associated with innate immune activation in animal models of inflammatory diseases and human neuropathology.

  View details for DOI 10.1021/jacsau.3c00435

  View details for PubMedID 38155640

  View details for PubMedCentralID PMC10751761

• Application of Machine Learning Driven Computational Approaches for Novel CNS PET Tracer Development Jackson, I., Luo, A., Webb, E., Zhang, B., Guo, A., Nagy, S., Shao, X., Kuo, R., Carlson, M., Alam, I., Rodriguez, A., Winton, W., Stauff, J., Kalita, M., Scott, P., James, M. ELSEVIER SCIENCE INC. 2023: S40-S41

  View details for Web of Science ID 001128725600053

• Magnetic Particle Imaging in Vascular Imaging, Immunotherapy, Cell Tracking, and Noninvasive Diagnosis MOLECULAR IMAGING Chandrasekharan, P., Kuo, R., Fung, K., Saayujya, C., Bryan, J., Yousuf, M., Fellows, B., Colson, C., Huynh, Q., Doyle, O., Hartley, A., Yousuf, K., Goodwill, P., Conolly, S. 2023; 2023

  View details for DOI 10.1155/2023/4131117

  View details for Web of Science ID 000956804400001