Joost Christiaan Haeck MS, Abstract Co-Author: Nothing to Disclose

Corrina De Ridder, Abstract Co-Author: Nothing to Disclose

Linda M Van Der Graaf BS, Abstract Co-Author: Nothing to Disclose

Mark Halberstadt, Abstract Co-Author: Nothing to Disclose

Marleen Melis, Abstract Co-Author: Nothing to Disclose

Marion De Jong PhD, Abstract Co-Author: Nothing to Disclose

Wytske Van Weerden, Abstract Co-Author: Nothing to Disclose

Monique R. Bernsen PhD, Presenter: Nothing to Disclose

Peptide Receptor Radionuclide Therapy (PRRT) promises highly specific tumor-targeting therapy with radiolabeled peptides designed to bind and radiate tumor cells expressing specific peptide receptors on the cell membrane. Prostate cancer (PC) is a candidate for PRRT using bombesin analogues as gastrin-releasing peptide receptors (GRPR) are over-expressed in androgen-dependent PC tumors. SPECT imaging of the PC295 xenograft revealed heterogeneous uptake of In-111 radiolabeled bombesin analog JMV, despite expression of GRPR throughout the tumor as assessed by in vitro autoradiography. We hypothesized that tumor vascularization and perfusion plays a crucial role in the efficient delivery of the radiolabeled peptides. Dynamic contrast-enhanced (DCE) MRI can be used to visualize tumor vasculature and quantify perfusion. Experiments were performed to see if MRI parameters can predict peptide uptake efficiency in PC xenografts.

Subcutaneous PC295 xenografts in 4 male NMRI nu/nu mice were imaged when the tumor reached a size of 1 cm3. Imaging was performed on a 7T animal MRI and animal SPECT. Black-blood, T1, T2, PD and T2* weighted MR images were acquired. Dynamic 3D T1 images were acquired with gadobutrol at a temporal resolution of 3 seconds and 0.2x0.2x1 mm voxel size.

SPECT images showed peptide uptake predominantly in the periphery of the tumors. Angiographic black-blood scans and T1W post-contrast scans did not show evidence of intra-tumoral vasculature. DCE curves of the PC295 tumor showed very little enhancement compared to the blood volume and surrounding muscle tissue. Peak contrast concentrations in the tumor were found after more than 2 minutes.

Neither black-blood scans nor post-contrast images showed signs of large intra-tumor vessels. Also, DCE-MRI parameter time to peak showed very slow signal enhancement, indicating poor perfusion of contrast agent in the tumor. Hyper-intense T2 images indicated high fluid content within the tumor contributing to lower perfusion. The maximum enhancement was highest at the tumor periphery, similar to the SPECT images. In conclusion, the heterogeneous peptide binding can be linked to slow perfusion and poor vascularization.

By using non-invasive techniques to predict therapy efficacy we aim to make a step forward in therapy mechanics for personalized treatment

Haeck, J, De Ridder, C, Van Der Graaf, L, Halberstadt, M, Melis, M, De Jong, M, Van Weerden, W, Bernsen, M, DCE-MRI as a Predictive Tool for Targeted Peptide Delivery Efficiency.  Radiological Society of North America 2011 Scientific Assembly and Annual Meeting, November 26 - December 2, 2011 ,Chicago IL. http://archive.rsna.org/2011/11009202.html