This project will explore the translational potential of a new PET molecular imaging probe [68Ga]PC-1001 for detecting very small cancers and distinguishing between localized and metastasized cancers in bone and soft tissue mouse models. [68Ga]PC-1001 will be evaluated for metastatic prostate (PC) and pancreatic (PaCa) cancers. Early detection of the most lethal PaCa with <5% survival for 5 years could improve patient survival by earlier intervention, currently an unmet clinical challenge. Bone metastases, the hallmark of advanced PC, occurring in ~80?90% of cases. Bone is a common metastatic site in a variety of other cancers including breast, prostate and lung, triggering severe bone pain, fracture, malignant hypercalcemia, infection and skeletal complications. Soft tissue metastases to liver, lung, and/or brain are indicators of poor prognosis and ultimately cause death for both PC and PaCa. Since no cancer cell specific positron emission tomography (PET) probe is available clinically, our goal is to develop a sensitive PET probe that can detect the smallest sizes of PaCa tumor metastasis and differentiate bone from soft tissue PC metastasis in mice. In preparation for the resubmission of this proposal, we successfully achieved the goals of detecting very small PaCa tumors (< 2 mm3) in KPC transgenic mice, and distinguishing PC tumor from neighboring bone tissues in a mouse model of human PC bone metastasis. With encouraging new data, we propose to: 1) compare the imaging profile of [68Ga]PC-1001/PET with [18F]FDG/PET in localized and metastatic PaCa using an immune-intact KPC transgenic mouse model; 2) detect PC bone metastasis by distinguishing between clusters of human cancer tissues in bone and the surrounding reactive mouse bone tissues in immune-deficient mice. Both models have been thoroughly established in our lab for observing localized tumor growth and soft tissue metastases (PaCa model) and cancer bone and soft tissue metastasis using ex vivo luciferase-tagged cells as experimental tools (PC model). The specificity of [68Ga]PC-1001 to cancer cells and their metastases to bone and soft tissues will be confirmed at the cellular level. The sensitivity of [68Ga]PC-1001/PET will then be compared with [18F]FDG/PET for cancer bone and soft tissue metastases in PaCa and PC models. The combined expertise of Dr. Pan's lab at the University of Virginia in chemical synthesis, molecular imaging and autoradiography, and Dr. Chung's lab at Cedars-Sinai Medical Center in a PaCa KPC and MiaPaCa models of local tumor growth and distant dissemination to surrounding tissues and in PC models of bone and soft tissue metastases ensure the likely success of the project. We anticipate that at the end of this phase I project [68Ga]PC-1001 will be ready for preclinical toxicity, pharmacokinetics (PK), and pharmacodynamics (PD) studies. We proposed to address following two specific aims in phase I part of this SBIR project.
Detection of early and metastatic cancer is a major challenge to clinicians to identify and confirm the disease for better treatment options and response, and to patients for loss of quality of life due to morbidity. Early detection of metastatic sites by cancer specific and sensitive molecular probe would alleviate these difficulties. Application of 68GaPC1001, a new PET/NIRF dual mode imaging probe would aid in the early detection, staging, prognosis, and evaluation of therapeutic responses in cancer, especially bone and soft tissue metastases.
