Superiority of 160 kV vs 6 MV X-ray irradiation combined with

heavy element radiosensitization

By: Sara N. Lim, Anil K. Pradhan, Sultana N. Nahar, Rolf F. Barth, Claudia Turro, Alycia M. Palmer, Erica H. Bell

and Xiaokui Mo

Outline of presentation

Background: X-ray radiotherapy and how can we improve it?

Low energy 160 kV vs 6000 kV (6 MV) X-rays

What is radiosensitization?

enhancing X-ray dose with heavy elements to kill malignant cells

Monte Carlo simulations on radiosensitization using heavy elements (high atomic number Z or HZ – review from earlier presentation).

Experiments: promising in vitro results

In vivo experiments in progress

Current Radiotherapy

6 MV clinical linac (Varian Clinac)

unfiltered spectrum: ~0-6000 keV (6 MeV)

• X-rays can not differentiate between tumor tissues and healthy tissues with or with out radiosensitization

• Reason for use: penetration

What if there was a way to increase the damage to tumor tissues that more than

makes up for the lack of penetration?

There is! With heavy element radiosensitization!

Dose Enhancement Factors

Geant4 results using 7ug/ml Pt for increase in dose deposition as a function of X-ray energy

160 kV

6 MV

In vitro experiments

F98 rat glioma cells:

Radiosensitized with relatively non-toxic HZ radiosensitizer or carboplatin

Irradiated with either 6 MV or 160 kV X-rays to test changes in surviving fraction (SF)

In vitro analysis Methods and materials

Clonogenic assay with Pt-sensitized F98 cells after broadband X-ray irradiation (160 kV Vs 6 MV, 7 Gy)

1.

2.

Radiosensitizers:

Pyridine Terpyridine Pt(II) complex (typ-Pt)

- low in vitro toxicity

- allows decoupling of chemotoxicity and radiotoxicity

- unexpectedly cytotoxic in vivo

Carboplatin

- common cancer therapeutic – well known cytotoxic range

- going to be used in in vivo study

Decrease in malignant cell survival after irradiation

varying amounts of radiosensitizer

no x-ray

6 MV

160 kV

no x-ray

6 MV

160 kV

Increase cell killing: Low Energy VS High Energy

160 kV

6 MV

radiation dose

Decrease in malignant cell survival after irradiationvarying radiation dose (with carboplatin)

No sig. difference

In vivo experiments

Non – therapeutic dose of carboplatin

103 F98 glioma cells

160 kV10 Gy

6 MV10 Gy

So, what will this experiment show?

In vivo experiments

Stay tuned for the sequel

Conclusion

In vitro experiments showed greater cell death with low energy X-rays

Radiosensitized rats treated with low energy X- rays SHOULD live longer

Thanks for listening!