Intracellular Paired Agent Imaging (iPAI) Enables Personalized Therapy Selection for Cancer Patients

ASPIRE Award (2018-2020)

Summer Gibbs, PhD, Oregon Health & Science University (Principal); Kimberley Samkoe, PhD, Dartmouth College; and Kenneth Tichauer, PhD, Illinois Institute of Technology

Summer Gibbs, PhD

Understanding how a drug will function in an individual patient is challenging. The available amount of a drug’s molecular target may vary from patient to patient, the drug may bind its target differently in each patient, and individual patients could respond uniquely to drug-target recognition. This variability makes developing drugs and choosing treatments for specific patients unpredictable. There are currently no optimal model systems to address this issue. Dr. Summer Gibbs of Oregon Health & Science University is working collaboratively with teams from Dartmouth College and the Illinois Institute of Technology to develop a system that will predict a therapy’s effectiveness and uncover potential toxic side effects. This method, called intracellular paired agent imaging (iPAI), makes use of fluorescently labelled molecules to quantify the presence of intracellular drug targets, drug accumulation, and protein signaling in tissues derived directly from the patient. iPAI will provide information on drug behavior simultaneously across a pathway, link target binding with pharmacokinetic response, and ultimately predict an individual’s therapeutic outcomes. When used in the clinic, iPAI could improve cancer therapy selection and provide better understanding of resistance to treatment.

published research

Samkoe KS, Schultz E, Solanki A, Wang L, Korber J, Tichauer KM, Gibbs SL. Simultaneous Extracellular and Intracellular Quantification of EGFR Using Paired-Agent Imaging in an In Ovo Tumor Model. Proc SPIE Int Soc Opt Eng. 2019.

Solanki A, Wang L, Korber J, McMahon N, Tichauer K, Samkoe KS, Gibbs SL. Intracellular Paired agent Imaging Enables Improved Evaluation of Tyrosine Kinase Inhibitor Target Engagement. Proc SPIE Int Soc Opt Eng. 2020.

McMahon NP, Solanki A, Jones J, Kwon S, Chang YH, Chin K, Nederlof MA, Gray JW, Gibbs SL. Fluorescent Imaging for In Situ Measurement of Drug Target Engagement and Cell Signaling Pathways. Proc SPIE Int Soc Opt Eng. 2020.

Tichauer KM, Wang L, Solanki A, Korber JR, Gibbs SL, Samkoe KS. Noninvasive in vivo mapping of intracellular signaling proteins using a pairing of targeted and untargeted fluorescently labeled small molecule kinase inhibitors. Progress in Biomedical Optics and Imaging. 2020.

Henderson ER, Xu X, Pogue BW, Samkoe KS, Anderson ME. Osteosarcoma mineralization changes on radiographs have moderate correlation to chemotherapy response using bone subtraction methodology. Annals of Joint. 2020.

Sadeghipour N, Rangnekar A, Folaron M, Strawbridge R, Samkoe K, Davis S, Tichauer K. Prediction of optimal contrast times post-imaging agent administration to inform personalized fluorescence-guided surgery. J Biomed Opt. 2020.

McMahon NP, Solanki A, Wang LG, Montaño AR, Jones JA, Samkoe KS, Tichauer KM, Gibbs SL. TRIPODD: a Novel Fluorescence Imaging Platform for In Situ Quantification of Drug Distribution and Therapeutic Response. Mol Imaging Biol. 2021.

Wang LG, Montaño AR, Combs JR, McMahon NP, Solanki A, Gomes MM, Tao K, Bisson WH, Szafran DA, Samkoe KS, Tichauer KM, Gibbs SL. OregonFluor enables quantitative intracellular paired agent imaging to assess drug target availability in live cells and tissues. Nat Chem. 2023.

Reed MS, Ochoa M, Tichauer KM, Weichmann A, Doyley MM, Pogue BW. Mapping estimates of vascular permeability with a clinical indocyanine green fluorescence imaging system in experimental pancreatic adenocarcinoma tumors. J Biomed Opt. 2023.