Ferdinand Frauscher MD, Presenter: Nothing to Disclose

Hannes Gradl MD, Abstract Co-Author: Nothing to Disclose

Leo Pallwein MD, Abstract Co-Author: Nothing to Disclose

Dieter Zur Nedden MD, Abstract Co-Author: Nothing to Disclose

Helmut Klocker PhD, Abstract Co-Author: Nothing to Disclose

Iris Eder PhD, Abstract Co-Author: Nothing to Disclose

Andrea Klauser MD, Abstract Co-Author: Nothing to Disclose

et al, Abstract Co-Author: Nothing to Disclose

Previous studies have shown that the downregulation of androgen receptor (AR) expression with an antisense oligodeoxynucleotide (ODNasAR) results in significant inhibition of prostate tumor growth in vitro as well as in vivo. In the present work, we studied the usefulness of microbubble-enhanced ultrasound (US) to direct the ODNasAR into prostate cancer cells and xenograft tumors.

The ODNasAR was charge-coupled onto the lipid surface of cationic contrast agent microbubbles. The ODN was delivered into LNCaP human prostate cancer cells in vitro or human prostate xenografts in nude mice in vivo by bursting loaded microbubbles using low frequency US (2.0 MHz) with a high mechanical index, respectively.

Transfer of the ODNasAR with microbubble-enhanced US into LNCaP cells in vitro resulted in significant downregulation of AR expression and induction of apoptosis. In vivo, uptake of a digoxigenin-labeled ODNasAR was found in human prostate xenografts after intravenous and intratumoral injection of loaded microbubbles and subsequent exposure of the tumor to US, respectively. Uptake of the ODNasAR in the tumor tissue was associated with a reduction in AR expression. By contrast, untreated collateral control tumors in the same mouse showed significantly lower uptake of the ODNasAR than the treated tumor, pointing out that treatment was highly focused to the US-exposed tumor. On the other hand, transfer of the ODNasAR into tumor cells was also achieved with US alone both, in vitro and in vivo. However, transfection efficiencies were slightly higher when the ODNasAR was delivered with US in combination with microbubbles.

This study shows that microbubble-enhanced US may be a feasible strategy to deliver antisense ODNs into prostate tumors in vivo.

Microbubble-enhanced US seems to be a feasible strategy to deliver antisense ODNs into prostate tumors and to offer a new therapeutic approach for prostate cancer.

Frauscher, F, Gradl, H, Pallwein, L, Zur Nedden, D, Klocker, H, Eder, I, Klauser, A, et al, , Microbubble-enhanced Ultrasound to Direct an Antisense Androgen Receptor Oligonucleotide into Prostate Tumors.  Radiological Society of North America 2006 Scientific Assembly and Annual Meeting, November 26 - December 1, 2006 ,Chicago IL. http://archive.rsna.org/2006/4433808.html