Abstract: PNFLBA-14
Sources of Funding: Funds from Stephenson Cancer Center

Introduction

Early detection of bladder cancer metastases might provide the potential for early treatment of metastatic disease. We previously reported on the use of a bladder tumor-binding peptide (BTBP)2 coupled to a Gd-DOTA MRI contrast agent (BTBP-probe)3 delivered intravesically to visualize bladder cancer growing on the bladder surface of an orthotopic mouse model, In this new report we demonstrated the use of this probe delivered intravenously to detect micrometastic spread of cancer to distant organs._x000D_

Methods

MRI Studies: MRI experiments were done on a Bruker Biospec 7.0 Tesla/30 cm horizontal-bore imaging system. Multiple abdominal region 1H?MR image slices were taken using a RARE multislice (repetition time (TR) 1.3 s, echo time (TE) 9 ms, 256x256 matrix, 4 steps per acquisition, 3x3 cm2 field of view, 0.75 mm slice thickness). Mouse abdominal organs were imaged at 0 (pre-contrast) and at 3-4 hours post-contrast agent injection. Mice were injected intravenously with the BTBP-Gd-DOTA contrast agent (100µl/mouse; 50µmol/L). T1-weighted images were obtained using a variable TR (repetition time) spin-echo sequence (TR, 200-1600 ms; TE, 15 ms; NA, 2). Pixel-by-pixel relaxation maps were reconstructed from a series of T1-weighted images using a nonlinear two-parameter fitting procedure. The T1 value of a specified region-of-interest (ROI) was computed from all the pixels in the identified ROIs. MRI scans were obtained 6-7 weeks post-implantation of bladder tumors to identiy metastatic lesions. _x000D_

Results

Molecular MRI (mMRI) was used to detect the presence of the BTBP-probe via a substantial decrease in T1 relaxation, measured as T1 relaxation difference, within tumor regions of mice administered the BTBP-probe (p<0.05) compared to the controls. Both primary and metastatic tumors were detected._x000D_

Conclusions

We used mMRI to show for the first time non-invasive in vivo early detection of bladder tumor metastases in a mouse model for bladder carcinoma. Using mMRI with a bladder tumor-binding peptide targeted probe provides the advantage of in vivo image resolution and spatial differentiation of regional events in early detection of bladder cancer metastases._x000D_

Funding

Funds from Stephenson Cancer Center