PARENT SESSION
1:30 PM to 3:30 PM
Wednesday, April 24, 2002
Poster Session 35 Other
Room: Nevada Exhibition Center

(P39-369) Methotrexate Enhances Potential of 5-[¹²⁵I]Iodo-2'-deoxyuridine in the Treatment of Neoplastic Meningitis.

Kassis, Amin^*,1, Xue, Lanny¹, Butler, Nicholas¹, Kirichian, Agop¹, Adelstein, James¹, ¹ Department of Radiology, Boston, MA

ABSTRACT-
Methotrexate (MTX) is used clinically to treat neoplastic meningitis. This antimetabolite also enhances the in-vitro and in-vivo uptake of the thymidine analog 5-[¹²⁵I]iodo-2'-deoxyuridine (¹²⁵IUdR). We had previously demonstrated that the sequential administration of the maximum tolerated doses (MTD) of these two agents (MTX-¹²⁵IUdR) in rats bearing intrathecal (i.t.) TE-671 human rhabdomyosarcoma significantly augmented the therapeutic efficacy of this Auger-electron-emitting radiopharmaceutical. We have now assessed whether three and six cycles of MTX and ¹²⁵IUdR at 1/10^th the MTD (i.e. 0.2 mCi) are therapeutically efficacious. Nude rats were injected with TE-671 cells through an i.t.-placed catheter. Three days later, the animals were injected i.t. with (i) saline (daily, 6 or 12 x), (ii) 31 g MTX (every other day, 3 or 6 x), (iii) 0.2 mCi or 2.0 mCi ¹²⁵IUdR (every other day, 3 or 6 x), and (iv) 31 g MTX and 0.2 mCi or 2.0 mCi ¹²⁵IUdR on alternating days (3 or 6 x). Probability of the onset of paralysis was determined as a function of time and the data were fitted to determine the medians (M) and statistical significance thereof. The data show that (i) the injection of MTX leads to a modest increase in the onset of paralysis (M_2x = 27 d; M_3x = 33 d; M_6x = 38 d; vs M_saline = 22 d), (ii) the administration of 0.2 mCi ¹²⁵IUdR is moderately more effective (M_3x = 36 d; M_6x = 45 d), (iii) the injection of 2 mCi ¹²⁵IUdR results in a substantial delay in the onset of paralysis (M_2x = 53 d; M_3x = 60 d), (iv) the sequential administration of MTX-¹²⁵IUdR (2 mCi) increases the therapeutic efficacy of ¹²⁵IUdR (M_2x = 82 d - 30% cure), and (v) the successive injection of MTX and ¹²⁵IUdR (0.2 mCi) is also quite effective in the therapy of this disease (M_3x = 54 d; M_6x = 90 d - 44% cure). We conclude that the intrathecal injection of MTX-¹²⁵IUdR at 1/10^th the MTD is therapeutically quite efficacious and can cure rats bearing i.t. tumors.

KEYWORDS: iodine-125, cancer therapy, intrathecal tumors, Auger electron emitters