Theranostic and Contrast Agent Development Lab

The UW Theranostic and Contrast Agent Development Lab is involved in the design, synthesis, and evaluation of novel targeted molecular imaging agents for computed tomography, magnetic resonance, and nuclear medicine including PET and SPECT as well as therapeutic radiopharmaceuticals. Our design strategy is based on a biochemical approach, whereby naturally occurring compounds known to be stored and or metabolized in the organ or tissue of interest serve as carriers for the radiologic moiety.

Our pan-cancer phospholipid tumor delivery platform has afforded a variety of new imaging and therapy agents active in multiple modalities including MRI (Gd-NM600), nuclear medicine (NM404/600), visible and near infrared optical, and a new tumor selective CT contrast agent under development. Radioiodinated (I-124/131) NM404 has been examined in over 6 clinical trials in multiple tumor types and radiometal labeled NM600 is expected to begin a clinical phase 1 trial in in advanced cancer patients in Q2, 2025. Our current NIH P01 grant was the first ever, large P01 grant funded by the NCI in the field of theranostics. Based on early findings in our collaborative laboratories, the premise of this work is to define the role of low dose targeted radionuclide therapies to stimulate the immune system against cancer cells and to induce immune memory to prevent recurrence of cancers once they are treated.

We have also discovered that low-dose TRT can prime the tumor immune microenvironment and significantly expand the scope and efficacy of current immunotherapies including checkpoint inhibitors. Our technologies are covered by over 50 US and international patents and licensed to two theranostic companies founded by Dr. Weichert.

The lab is unique in that we perform all synthesis, analysis, formulation, and pharmacokinetic evaluation as well as multimodality imaging totally within our group. Moreover, we work very closely with clinical and preclinical collaborators in immunology, radiobiology, and dosimetry here at UW. We are fortunate to have an extremely strong and cooperative association with cancer biologists on campus who have developed a variety of relevant cancer models. Dr. Weichert also founded the UWCCC Small Animal Imaging and Radiotherapy facility which is one of the strongest such facilities in the US. This facility allows us to seamlessly translate agents to clinical status.

Research

Targeted Design and Delivery of Cell Selective Imaging Agents for Computed Tomography (CT), Nuclear Medicine, PET, and Magnetic Resonance (MR)

CT and MRI Contrast Agents: CT projects include the development of polyiodinated lipophilic agents for hepatocytes-selective imaging as well as blood pool agents for CTA (angiography) and lymphography. MR interests utilize the same lipoprotein-like vehicle to deliver gadolinium chelates to hepatocytes for tumor imaging and a blood pool version may prove useful for detecting and characterizing atheroschlerotic plaques and other vascular anomalies. Utilizing a targeted delivery approach coupled with design and development of appropriate agents represents a significant enhancement over currently available imaging agents in all diagnostic modalities. We can now easily detect sub-300 micron liver tumors in live mice using the ImTek microCT scanner. Finally, combining the hepatocyte-selective ITG with a long acting radiopaque blood pool agent to temporarily enhance the vessels affords ultra-high-resolution liver tumor images. As a result of these studies, the surface of the chylomicron remnant-like carrier was modified in order to delay hepatocyte uptake thus resulting in prolonged blood pool activity (up to three hours). Combining these two versions of the ITG emulsion has eliminated the need to administer a subsequent small dose of urographic agent to get the highest contrast images of the tumor margins. An MRI blood pool agent is also under development. Such blood pool-selective agents may have widespread clinical use in CTA, MRA, cardiac, and atheroschlerotic conditions. Installation of a research MicroCT scanners has been vital toward further development of the hepatocyte-selective CT as well as CT and MR blood pool agents. Many of the initial CT imaging experiments in rodent models have been completed on these scanners at ultra high resolutions less than 20 micrometers. Moreover, ultra-high resolution blood pool imaging studies coupled with 3D reconstruction of the data may lead to very early detection and or characterization of atheroma or other vascular abnormalities. Such ultra high-resolution studies in rodents are not currently possible on large gantry clinical scanners. Results obtained on the MicroCT scanners may, however, provide a window to the future capabilities of our new agents as the resolution of commercial scanners continues to improve.

Tumor Selective Nuclear Medicine/PET Agents

Radioiodinated phospholipid analogs have proven useful in gamma camera imaging of a variety of human tumor xenografts and spontaneous tumor models in rodents. A promising second-generation analog, NM404, is currently undergoing clinical evaluation in lung cancer patients. The agent, which has shown remarkable tumor cells retention in 25/25 tumor models, can be defined as a diapeuticTM agent (Cellectar, LLC., Madison, WI) since it affords both tumor diagnostic and therapeutic potential. We are currently examining the tumor selectively of this agent in hyperplasia and neoplasia mouse models, and are initiating studies to evaluate its potential to predict tumor response to a variety of treatment modalities including external beam radiotherapy, chemotherapy, radio-frequency ablation, and surgical resection. We will soon be labeling this exciting compound with iodine-124, a new PET isotope with a 4 day half-life.

Collaborations

Other Collaborators

Behnam Badie, MD, Brain Model, Neurological Surgery
Pupa De Stasio, Synchrotron Spectro Microscopy, Synchrotron Radiation Center
William Dove, PhD, Intestinal Model, McArdle Laboratories
Michael Gould, PhD, Transgenic Rat Models, McArdle Laboratories
Paul Harari, MD, Squamous Cell Carcinoma Model, Human Oncology
Paul Lambert, PhD, Cervical Model, McArdle Laboratories
R. Jerry Nickles, PET Physics/Chemistry, Medical Physics
Amy Moser, PhD, Mammary Model, Human Oncology
Sharon Weber, MD, Liver/HCC Models, Surgical Oncology
George Wilding, MD, Prostate Model, UW Carbone Cancer Center

Partners