Using the clinical, pathological and imaging endpoints, predictive models will e developed using responses to uVESSEL model above. More specifically the objective response (dichotomous endpoint of yes or no) measured using PSMA-based PET/CT will be used as a dependent variable in a logistic regression model with response to uVESSEL model from above as an independent predictor to segregate uVESSEL responses into two groups corresponding to responders and non-responders to anti-angiogenic therapies.

Patient-derived uVESSEL models (from primary & metastatic sites) and incorporating patient-derived immune cells, will be tested for response to anti-angiogenic therapies including pazopanib, sunitinib, cabozantinib, and axitinib. Response will be quantified via multiple endpoints, e.g. vessel sprouting, PSMA expression, cell death.

Patient-derived uVESSEL models (from primary & metastatic sites) and incorporating patient-derived immune cells, will be tested for response to anti-angiogenic therapies including pazopanib, sunitinib, cabozantinib, and axitinib. Response will be quantified via multiple endpoints, e.g. vessel sprouting, PSMA expression, cell death. Two subjects had data collected and were assessed.

PET standardized uptake value (SUV) is defined as:

SUV = C(T) / (injection dose [MBq]/patient's weight [kg])

which represents the tumor or tissue radiotracer concentration at a point in time C(T) relative to the total concentration of radiotracer activity in the entire patient (total injected dose of radioactivity per kilogram of the patient's body weight), with body weight used as a surrogate for a distribution volume of radiotracer.

Maximum SUV (SUVmax) is the maximum or highest radiotracer activity within a defined ROI.

Bone Metastases

Soft tissue metastases

Compare PSMA imaging to histopathological endpoints which include tumor vascular density, immunohistochemical staining for PSMA and neovascularization (CD105, CD31 markers)

Data were not collected for Immunohistochemical PSMA staining due to termination of funding for this study due to low accrual (see section on limitation and caveats).

Compare PSMA imaging to histopathological endpoints which include tumor vascular density, immunohistochemical staining for PSMA and neovascularization (CD105, CD31 markers)

Data were not collected for Tumor vascular density due to termination of funding for this study due to low accrual (see section on limitation and caveats).

Compare PSMA imaging to histopathological endpoints which include tumor vascular density, immunohistochemical staining for PSMA and neovascularization (CD105, CD31 markers)

Data were not collected for CD105 and CD31 neovascularization due to termination of funding for this study due to low accrual (see section on limitation and caveats).

Patient-derived uVESSEL models (from primary & metastatic sites) and incorporating patient-derived immune cells, will be tested for response to anti-angiogenic therapies including pazopanib, sunitinib, cabozantinib, and axitinib. Response will be quantified via multiple endpoints, e.g. vessel sprouting, PSMA expression, cell death.

Patient tumor specimen were processed and positively selected for CD31 cells, for endothelial and epithelial cell fractions. Microphysiological models were established using the two cell populations using a mold casting strategy. Models were treated with therapeutic agents after 24 hr in culture and incubated with the agent for 72hr. Imaging with confocal microscopy was used to determine individual sprout numbers. Values were acquired from at least 2 independent experiments.

Using the clinical, pathological and imaging endpoints, predictive models will e developed using responses to uVESSEL model above. More specifically the objective response (dichotomous endpoint of yes or no) measured using PSMA-based PET/CT will be used as a dependent variable in a logistic regression model with response to uVESSEL model from above as an independent predictor to segregate uVESSEL responses into two groups corresponding to responders and non-responders to anti-angiogenic therapies.

Data were not collected to evaluate the predictive power and validation of the uVESSEL model due to termination of funding for this study due to low accrual (see section on limitation and caveats).

Patient-derived uVESSEL models (from primary & metastatic sites) and incorporating patient-derived immune cells, will be tested for response to anti-angiogenic therapies including pazopanib, sunitinib, cabozantinib, and axitinib. Response will be quantified via multiple endpoints, e.g. vessel sprouting, PSMA expression, cell death.

Data were not collected due to termination of funding for this study due to low accrual (see section on limitation and caveats).

Patient-derived uVESSEL models (from primary & metastatic sites) and incorporating patient-derived immune cells, will be tested for response to anti-angiogenic therapies including pazopanib, sunitinib, cabozantinib, and axitinib. Response will be quantified via multiple endpoints, e.g. vessel sprouting, PSMA expression, cell death. Two subjects had data collected and were assessed.

A version of the models without endothelial cells was generated to evaluate tumor (only) response to therapeutics. To this end, a luminescent reagent was used to assess the amount of ATP in the models, which can be correlated to the number of live cells in the model. Measurements were taken at day 0 and at day 4 (after 72h of treatment) and normalized to account for patient-specific ATP variations. Values were acquired from at least 2 independent experiments.