BIOLOGICAL EFFICIENCY OF A THERAPEUTIC PROTON BEAM: A STUDY OF HUMAN MELANOMA CELL LINE - PowerPoint PPT Presentation

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BIOLOGICAL EFFICIENCY OF A THERAPEUTIC PROTON BEAM: A STUDY OF HUMAN MELANOMA CELL LINE

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BIOLOGICAL EFFICIENCY OF A THERAPEUTIC PROTON BEAM: A STUDY OF HUMAN MELANOMA CELL LINE I. Petrovi 1, A. Risti -Fira1, D. Todorovi 1, L. Kori anac1, – PowerPoint PPT presentation

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Title: BIOLOGICAL EFFICIENCY OF A THERAPEUTIC PROTON BEAM: A STUDY OF HUMAN MELANOMA CELL LINE


1
BIOLOGICAL EFFICIENCY OF A THERAPEUTIC PROTON
BEAM A STUDY OF HUMAN MELANOMA CELL LINE
  • I. Petrovic1, A. Ristic-Fira1, D. Todorovic1, L.
    Koricanac1,
  • L. Valastro2 and G. Cuttone2
  • 1Vinca Institute of Nuclear Sciences, Belgrade,
    Serbia and Montenegro
  • 2Istituto Nazionale di Fisica Nucleare, LNS,
    Catania, Italy

2
Advantages of protons compared to conventional
radiation - targeting radiation dose precisely
into the tumour, - sparing neighboring healthy
tissue.
3
  • Physical qualities of protons
  • small lateral scattering,
  • energy loss per unit length linear energy
    transfer (LET)
  • increases while the proton slows down,
  • range directly proportional to energy,
  • depth-dose distribution
  • - slow increase of dose plateau region,
  • - rapid build-up to a sharp maximum almost at
    the
  • end of range the Bragg peak,
  • - distal swift fall-off.

4
Practical approach to deliver uniform dose over
large volume at a given depth
  • Spread-out Bragg peak (SOBP) modulation of
    proton energy at the price of a slight increase
    of the entrance dose.
  • Modulation of proton energy, i.e., range, is
    achieved by degrading initial proton energy which
    results in superimposition of a number of
    monoenergetic proton beams of closely spaced
    energies, thus the position of the Bragg peak is
    pooled back towards the beam source as energy is
    reduced.
  • The Bragg peak and SOBP have a higher LET than
    the beam entering the tissue.

5
National Association for Proton Therapy, USA
6
Goal
  • Evaluation of physical and radiobiological
    parameters of the CATANA (Centro di Adro Terapia
    e Applicazzioni Nucleari Avanzati) proton beam
    facility, used for the treatment of eye melanoma.
  • Assessment of parameters describing the level of
    cell radio-sensitivity and efficiency of
    different radiation qualities (highly ionising
    radiation - protons vs. conventional radiation -
    ?-rays) needed to analyse and predict success of
    therapeutic irradiations.

7
The CATANA (Centro di Adro Terapia e
Applicazzioni Nucleari Avanzati) treatment
facility, INFN - LNS, Catania, Italy
8
Irradiation conditions
  • Irradiations at 6.6, 16.3, 25.0 and 26.0 mm in
    Perspex (Polymethyl methacrylate - PMMA) within
    the SOBP of the 62 MeV proton beam (produced by
    the superconducting cyclotron at the CATANA
    treatment facility, INFN, LNS Catania).
  • Reference dosimetry plane - parallel PTW 34045
    Markus ionization chamber calibrated according to
    IAEA code of practice (IAEA-TRS-398 2000).
  • Single doses delivered to the cells 2, 4, 8, 12
    and 16 Gy, at dose rate of 15 Gy/min.
  • Irradiations with ?-rays, at the same dose
    levels, were performed using 60Co source at the
    Vinca Institute of Nuclear Sciences in Belgrade,
    at average dose rate of 1 Gy/min.
  • All cell irradiations were carried out in air at
    room temperature.

9
Bragg peak
  • Figure 1. Depth dose distribution of the Bragg
    peak in Perspex of the 62 MeV proton beam
    produced at the CATANA treatment facility in the
    INFN-LNS, Catania.

10
SOBP
  • Figure 2. Depth dose distribution of the
    spread-out Bragg peak in Perspex of the 62 MeV
    proton beam produced at the CATANA treatment
    facility in the INFN-LNS, Catania. Arrows
    correspond to irradiation positions at 6.6 mm
    (A), 16.3 mm (B), 25 mm (C) and 26 mm (D).

11
Table 1. Irradiation position parameters in SOBP
for HTB140 cells
Irradiation Depth in
Dose E position
Perspex (mm) ()
(MeV)
A 6.6
87.242.61 50.904.33
B 16.3
99.420.58
34.882.15 C
25.0 102.213.43
11.741.23 D
26.0
32.124.27 5.991.36
mean energy
12
Cell culture conditions
  • Irradiation of exponentially growing HTB140 human
    melanoma cells.
  • Plating efficiency (PE) for HTB140 cells -
    approximately 60 70 .
  • Doubling time (Td) for HTB140 cells - 242,7 h.

Biological assays
  • Cell viability
  • - clonogenic assay (CA),
  • - microtetrasolium (MTT) assay,
  • - sulforhodamine B (SRB) assay.

13
Assessment of radiobiological effects of protons
  • Surviving fraction as a function of dose and/or
    depth.
  • Surviving fraction at 2 Gy (SF2) level of
    radio-sensitivity.
  • Relative biological effectiveness (RBE)
    inactivation capacity of irradiated cells
  • RBE(2Gy, ?) - ratio of 2 Gy ?ray dose and the
    proton dose generating the same inactivation
    level as that of ?-rays,
  • strongly depends on LET, reaching its maximum
    value at 100 keV/µm, corresponding to proton
    energy of 65 keV.

High-LET radiations, i.e., protons and heavy
ions, have more efficient biological
effectiveness than low-LET radiations, such as
X-rays or ?-rays.
14
CA
Figure 3. Dose dependent surviving fractions,
estimated by clonogenic assay, of HTB140 melanoma
cells irradiated with ?-rays and protons.
Irradiation position within the proton spread-out
Bragg peak correspond to 6.6 mm (A), 16.3 mm (B),
25 mm (C) and 26 mm (D) depth in Perspex.
15
CA
SRB
MTT
Figure 4.
16
Table 2. SF2 values at different depths in SOBP
for HTB140 cells
Irradiation CA?
MTT?? SRB??? position
?-rays single 0.8740.074
0.8750.078 0.8480.054 protons A (6.6
mm) 0.8250.061 0.7740.033
0.8060.018 B (16.3 mm)
0.7480.103 0.6910.015
0.7220.022 C (25.0 mm)
0.5620.036 0.5200.015
0.5840.081 D (26.0 mm)
0.5780.064 0.5320.036
0.5960.011
? clonogenic assay, ?? microtetrasolium assay,
??? sulforhodamine B assay.
17
CA
Figure 5. Surviving fractions of HTB140 melanoma
cells irradiated at 2, 4, 8, 12 and 16 Gy as a
function of depth, estimated by clonogenic assay.
Irradiation position within the proton spread-out
Bragg peak correspond to 6.6 mm (A), 16.3 mm (B),
25 mm (C) and 26 mm (D) depth in Perspex.
18
CA
MTT
SRB
Figure 6.
19
Table 3. RBE(2Gy, ?) values at different depths
in SOBP for HTB140 cells
Irradiation CA?
MTT?? SRB??? position
A (6.6 mm) 1.390.06 1.890.09
1.320.07 B (16.3 mm)
2.140.11 2.760.18
2.020.14 C (25.0 mm) 4.630.23
5.280.31 3.320.21
D (26.0 mm) 4.260.28
4.890.37 3.080.27
? clonogenic assay, ?? microtetrasolium assay,
??? sulforhodamine B assay.
20
Conclusions
  • Surviving fractions at 2 Gy (SF2), throughout the
    whole spread out Bragg peak (SOBP), indicated
    high level of radio-resistance of HTB140 cells.
  • For the dose range comprising small and
    therapeutic doses, relatively high level of
    survival was revealed, moderately decreasing when
    changing irradiation position from the proximal
    to the distal end of SOBP.
  • A rather important rate of the fall of survival
    at small doses (2 and 4 Gy) was significantly
    reduced for therapeutic doses (8 to 16 Gy),
    implying even relatively higher level of
    radio-resistance than pointed out by SF2.

21
Conclusions
  • RBE values indicated significant level of proton
    induced cell inactivation, even though it was
    shown that HTB140 cells are among the most
    radio-resistant cells.
  • RBE values considerably increased when
    approaching the distal end of SOBP.
  • At the distal declining edge of SOBP, where the
    dose intensity was less than half of the full
    dose intensity of SOBP, the killing ability of
    protons was close to that observed at the distal
    end of SOBP.
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