A highly specific NIRF PET probe for the detection of cancer and metastases

This project will explore the translational potential of a new PET molecular imaging probe Ga PC for detecting very small cancers and distinguishing between localized and metastasized cancers in bone and soft tissue mouse models Ga PC will be evaluated for metastatic prostate PC and pancreatic PaCa cancers Early detection of the most lethal PaCa with andlt survival for years could improve patient survival by earlier intervention currently an unmet clinical challenge Bone metastases the hallmark of advanced PC occurring in 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 andlt mm 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 compare the imaging profile of Ga PC PET with F FDG PET in localized and metastatic PaCa using an immune intact KPC transgenic mouse model 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 Ga PC to cancer cells and their metastases to bone and soft tissues will be confirmed at the cellular level The sensitivity of Ga PC PET will then be compared with F FDG PET for cancer bone and soft tissue metastases in PaCa and PC models The combined expertise of Dr Panandapos s lab at the University of Virginia in chemical synthesis molecular imaging and autoradiography and Dr Chungandapos 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 Ga PC 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 GaPC 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