Purpose Hypoxia-inducible factor-1 alpha (HIF-1 α) expression has been linked with increased mortality and treatment failure in various cancers. The purpose of this study was to test the hypothesis that transcatheter arterial embolization (TAE) induces expression of HIF-1 α within the same rabbit VX2 liver tumor. Materials and Methods Seven VX2 tumors were grown in the livers of 5 New Zealand white rabbits. Ultrasound guided biopsies were taken before and 10 min after TAE from all tumors. Pre- and post- TAE tumor biopsy specimens along with post- TAE whole liver tumor sections were stained with HIF-1 α antibody and analyzed for percentage of HIF-1 α positive nuclei using a spectral unmixing system mounted on a high powered microscope. Statistical data comparisons were performed using Wilcoxon signed-rank test (alpha=0.05). Results TAE of liver tumors resulted in a statistically significant increase in the mean percentage of HIF-1 α expression. The mean percentage of HIF-1 α positive stained nuclei increased from 23 % ± 3.5% in pre- TAE biopsy specimens to 41% ± 8.7% (p< 0.02) in post- TAE biopsy specimens. The increase was even more significant when mean percentage of HIF-1 α positive stained nuclei from the same pre- TAE biopsy specimens were compared to sections from post- TAE whole tumor specimens [60% ± 8.9% (p<0.02)]. Conclusions The study revealed that hypoxia caused by TAE of VX2 liver tumors activates HIF-1 α, a transcription factor that in turn regulates other pro-angiogenic factors.

The authors recommend (a) the use of fresh VX2 cell suspension for percutaneous injection in the hind limbs of rabbits to maintain the VX2 cell strain and (b) the surgical implantation of freshly harvested VX2 tumor fragment into the liver parenchyma to establish liver tumors.

Nanoconjugates composed of TiO 2 nanoparticles, DNA oligonucleotides and a gadolinium contrast agent were synthesized for use in magnetic resonance imaging. Transfection of cultured cancer cells with these nanoconjugates showed them to be superior to the free contrast agent of same formulation with regard to 1) intracellular accumulation, 2) retention and 3) subcellular localization. Our results have shown that 48 hours after treatment, the concentration of gadolinium in nanoconjugate treated cells was 1000 fold higher compared to cells treated with contrast agent alone. Consequently, T 1 -weighted contrast enhancements were observed in cells treated with nanoconjugates but not in cells treated by the contrast agent alone. This type of nanoconjugate with increased retention time, Gd accumulation and intracellular delivery may find its use in gadolinium neutron-capture cancer therapy.

Microsphere tracking during radioembolization may permit real-time verification of delivery and detection of extrahepatic shunting.

Transcatheter intraarterial perfusion (TRIP)-MRI is an intrapro-