Peptide-based Nanoparticle for Positron Emission Mammography

Fangy Peng, M.D., Ph.D.
University of Texas Southwestern Medical Center

This project seeks to develop 64CU-DOTA-peptide–conjugated nanoparticles for the diagnostic imaging of Her2-positive breast cancer with positron emission mammobraphy. An Her2-specific peptide has been developed using phage display. These novel nanoparticles will be studied in orthotopic breast carcinoma xenograft models in mice.

NUSPIONs for MRI/PET Imaging of Prostate Cancer

Xiankai Sun, Ph.D.
University of Texas Southwestern Medical Center

This project will evaluate the efficacy of theragnostic nanoparticles consisting of γ- or β+ -emitting nuclides incorporated into the superparamagnetic iron oxide particles (NUSPIONs). These novel nanoparticles avoid in vivo demetallation while imparting the iron oxide nanoparticles with the superior sensitivity of PET for multimodality imaging. The dual modality (MRI/PET) imaging capability of NUSPIONs will be evaluated in an orthotopic prostate carcinoma xenograft model in mice.

Novel PET/MRI Probes for Neuroendocrine Tumors

Orhan Oz, M.D., Ph.D.
University of Texas Southwestern Medical Center

This project aims to develop targeted PET/MRI probes for imaging tumors that express the GLP-1R glucagon receptor (e.g., insulinomas). The chelator core selectively forms a neutral complex with 68Ga for PET, multiple copies of Gd(III)-DOTA for MRI and three constructs of a bicyclic glucagon-like peptide 1 analog for specific imaging of tumors that express GLP-1R. The project goals are to synthesize and characterize the trivalent constructs, evaluate the dual metal complexes in vitro and evaluate the PET/MRI probes in normal mice and in a spontaneous multistage insulinoma transgeneci mouse model (Rip1Tag2).

Combining Gene Therapy and Nanomedicine to Enhance the Therapeutic Potential of Tumor-specific T Cells

King Li, M.D., M.B.A.
The Methodist Hospital–Houston

This project will evaluate the efficacy of PET/CT imaging of gold nanoparticles and 64Cu-labeled T cells targeted to c-MET+ lung cancer via a c-MET–specific chimeric antigen receptor transduced into the T cells. Mice bearing lung tumors will be tested for the ability of c-Met–specific 64Cu-labeled T cells bearing gold nanoparticles to target hypoxic tumors. Other goals are to induce mild intracellular hyperthermia (via lasers or RF) to conditionally activate either the sr39HSV1-tk reporter gene for PET imaging with 18F-FEAU or T cells for IL-15 or bradykinin secretion, the latter with the aim of enhancing T-cell survival and antitumor effects or improving the biodistribution of liposomal-encapsulated doxorubicin via induction of vascular leaks.

Enzyme-activatable Agents for Tumor Imaging and Therapy

Ching Tung, Ph.D.
The Methodist Hospital–Houston

This project will evaluate new PET imaging agents consisting of a protease substrate peptide (e.g., cathepsin B substrate), a CPP signal (e.g., Tat peptide) and an α-, β-, γ-, or positron-emitting radionucleotide (e.g., 64Cu). The presence of cathepsin B (or related protease) in tumors would activate this triple compound, allowing the released CPP-radionuclie component to enter the targeted cells. The proposed constructs could carry imaging and therapeutic radionuclides. Tumors could be visualized by PET/CT or SPECT/CT. Subsequent pulsed high-intensity focused ultrasound-guided imaging will be used to further enhance the controlled delivery of therapeutic radionuclides.

Tumor Stratification and Personalized Medicine by CT Imaging

Ananth Annapragada, Ph.D.
University of Texas Health Science Center–Houston

This project aims to develop CT-based diagnostic and prognostic markers to characterize individual tumors and help to identify optimal treatment strategies. This proposal seeks to extend previous findings that the uptake of nanoparticle-based CT contrast agent predicts response to nanoparticle-based therapy in breast cancer to ovarian and lung tumors in rats. The nanoparticle-based CT agent uptake will be compared to 18F-FDG PET/CT imaging results and to proteomic signatures of the tumor, lending insight into the mechanisms of vascular permeability and heterogeneity in the growth and proliferation of individual tumors.


Imaging EGFR Expression and Activity with PET/CT with 18F-PEG6-IQA in NSCLC Patients

Donald A. Podoloff, M.D., and David Stewart, M.D.
MD Anderson Cancer Center

This project involves a Phase I/II trial to assess the safety and initial feasibility of 18F-PEG6-IQA PET/CT imaging in patients with NSCLC. The limited efficacy of novel tumor-targeted therapies such as eGFT inhibitors underscores the need for novel diagnostic imaging approaches to identify patients with NSCLS with significantly activated EGFR signaling who may benefit from such inhibitors.

Monitoring Trafficking of sr39HSV1-tk–transduced T cells for BMT with 18F-FEAU PET/CT

Juri Gelovani, M.D., Ph.D.
MD Anderson Cancer Center

The efficacy of bone marrow transplantation and adoptive T-cell transfer for therapy of leukemia is oftenhampered by the uncertainty of cellular trafficking, viability and risk of developing graft-vs-host disease. The ultimate goal of this Phase I/II trial is to assess the safety and efficacy of PET/CT imaging with 18F-FEAU for monitoring the spatial and temporal dynamics of T-cell trafficking and detecting graft-vs-host disease in patients undergoing these therapies.

68Ga-DOTA-BMTP-11 PET/CT/MRI for Imaging Prostate Cancer Vasculature-targeted Therapy

Renata Pasqualini, Ph.D., and Wahid Arap, M.D., Ph.D.
MD Anderson Cancer Center

The novel therapeutic agent Bone Metastasis Targeting Peptide-11, in which an IL-11R–selective peptide motif is combined with the pro-apoptopic 14-mer KLAKLAKKLAKLAK, is in Phase I clinical trials. This project aims to develop an imaging agent, 68GA-DOTA-BMTP-11, for PET/CT to visualize the binding, distribution and changes in the interleukin-11 receptor during tumor development and treatment. Plans include IND-driven GLP toxicology studies in rodents and pharmacokinetics and radiation-dosimetry studies in non-human primates. GMP-grade DOTA-BMTP-11 peptide has already been acquired. A Phase I trial will assess the safety and initial feasibility of 68GA-DOTA-BMTP-11 PET/CT for men with metastatic prostate cancer.

Hemodynamic and Oxygen-metabolic Imaging of Tumor Treatment Response with fMRI and 15O PET

Peter Fox, M.D., Timothy Duong, Ph.D., Chris Peng, Ph.D. and M. Duff Davis, Ph.D.
University of Texas Health Science Center–San Antonio

This project develops functional MRI (fMRI) imaging methods to non-invasively assess tumor hemodynamics and oxidative metabolism, with an emphasis on detection of tumor response to treatment. 15O PET is the gold-standard for quantitative assessment of tissue hemodynamics and oxygen delivery and consumption, but requires an on-site cyclotron. Functional MRI is widely available and has the potential to provide many of these same measures, but requires considerable development and validation. In this project, a variety of fMRI measures (e.g., BOLD, ASL, VASO and others) will be optimized for tumor imaging and validated by comparison to 15O PET. Assessments will proceed concurrently in rodents and humans with a variety of tumor types.