Potential application of boron neutron capture therapy (BNCT) on differentiated thyroid cancer.

DAGROSA, MA; THOMASZ, L; CARPANO, M; PERONA, M; NIEVAS, S; THOP, S; POZZI, E; JUVENAL, G; PISAREV , M

Paris

Congreso; 14th International Thyroid Congress,; 2010

American Thyroid Association (ATA)

Introduction: Despite the fact that differentiated thyroid cancers have a benign prognosis it is not unusual that when they relapse they may lose iodide uptake and become more aggressive and difficult to control. In previous reports we have demonstrated the efficacy of BNCT to control and cure undifferentiated thyroid cancer in an experimental model. BNCT is based on the selective uptake of 10B-borophenylalanine (BPA) by tumors. The irradiation with an appropriate neutron beam activates 10B to 11B which decays releasing alpha particles and 7Li with a high ionizing activity, and therefore will kill tumoral cells. In this study we have analyzed the potential application of BNCT to differentiated thyroid cancer. In three patients with relapsed papillary thyroid cancer we found a selective uptake of BPA. Materials and Methods: Human cell lines of follicular (WRO) and papillary (TPC-1) thyroid cancer were utilized. The FRTL-5 cell line was used as a control. The cells were grown in RPMI or modified DMEM media supplemented with 10% bovine fetal serum. The uptake of 125 I and BPA (6.93 mM) were studied “in vitro”. 10B was determined by inductive coupled optical emission spectroscopy (ICP-OES).  The WRO cells were irradiated with either thermal neutrons (flux: 7.5 109 n/cm2 sec) or using a 60Co source with a rate of 1 Gy/min. The survival fraction as a function of the total physical dose (0-8 Gy) was calculated. “In vivo” studies: cells were implanted into the right back flank of NIH-nude mice, 20-25 g body weight. Growth of the tumors was assessed with a calliper and volume was calculated. BPA was injected via ip (350 mg/Kg bw) and the animals were sacrificed after 30, 60 or 120 min. Results: The radioactive 125I uptake was significantly lower in the tumor cells than in normal cells (p<0.01). The ratios between FRTL-5 / WRO and FRTL-5/TPC-1 were 305 and 76 respectively. On the contrary the boron intracellular concentration ratios between WRO/FRTL-5 and TPC-1/FRTL-5 were 5.4 and 2.6, respectively, showing the selective uptake of BPA. The irradiation of WRO cells showed that the viability decreased as a function of the total physical dose for all the treatment and that BNCT using BPA is the more effective treatment, compared to neutrons alone or the gamma rays. The animals implanted with 1.5 10 6 cells showed a peak of around 17 ppm at 1 hr post injection. The ratios between tumor and normal surrounding tissues (blood and distal skin) were 2.6 and 2, respectively. Conclusions:  The cell lines studied showed a biological behaviour similar to that of the patients that we have studied and open the possibility of treating relapsed differentiated thyroid cancer by BNCT.