KSA-NIH and KUSCO will hold Dr. In Soo Shin (Clinical Center, NIH) for the
September session of KSA-KUSCO Seminar.
Time: September 2, 2009 (Wednesday), 11:40 am - 1:00 pm
Place: 9th Floor Conference Room (9S235) of Bldg. 10, NIH-Bethesda Campus
Title: Tumor Therapy Development as a Translational Research -
Radiopharmaceutics to Cure and Imaging Cancer.
Part I. Synergistic Effect of Taxol and Enhanced Delivery effect of PULSED
high intensity focused ultrasound (p-HIFU) when combined with
radioimmunotherapy. J Nucl Med. 2009;50(S2): 131P
Part II. investigation of ÉøvÉ¿3 expression ON neo-vasculature as a predictive
marker of therapeutic response. J Nucl Med. 2009;50(S2): 151P
Abstracts:
PartI: Synergistic Effect of Taxol and Enhanced Delivery effect of PULSED
high intensity focused ultrasound (p-HIFU) when combined with
radioimmunotherapy.
Objectives: To investigate the effect of Taxol and p-HIFU on the therapeutic
efficacy of 90Y-MX-B3 mAb in the treatment of the Ley -positive A431 tumors.
Methods: When A431 tumors xenografted s.c.on the flank of nude mice reached
200 mm3, the mice (n=3~7/group) received i.v. 90Y-B3 alone(60 É Ci or 100 É Ci
/150 É g B3), i.p. Taxol alone(40 mg /Kg), both agents(90Y-B3 and after 24hr, Taxol), or no treatment. To investigate p-HIFU effect, the p-HIFU exposures were given first, and within 10 min, the mice received i.v.
90Y-labeled B3. Mice were euthanized when the tumor size was 2 cm in diameter.
Results: The control mice had a median survival time of 5 days.
The Taxol treatment delayed tumor growth with a median survival time of 17days. The 90Y-B3 treatment showed a dose-dependent response with a median survival time of 18 days for the 60 É Ci B3 group and 29 days for the 100 É Ci
B3 group. The combined therapy involving 60 É Ci B3 and 100 É Ci B3 with Taxol
showed a striking synergistic effect in shrinking tumor and prolonging the survival time. The p-HIFU combined with 60 É Ci B3 treatment inhibited tumor growth, producing a median survival time of 26 days, comparable to that of animals treated with 100 É Ci B3 alone. On day 120, 2 of 5 mice treated with a combined therapy of 60 É Ci B3 with Taxol, and 6 of 6 mice treated with a combined therapy of 100 É Ci B3 with Taxol were alive with no tumor.
Conclusion: This synergistic effect of Taxol and the delivery enhancing effect of p-HIFU to the radioimmunotherapy warrant further studies in other tumor models.
Part II. investigation of ÉøvÉ¿3 expression ON neo-vasculature as a predictive
marker of therapeutic response.
Objectives: To quantify the ÉøvÉ¿3 receptor expression on tumor-induced neovasculature with 111In-DOTA-E-[c(RGDfK)]2 during a course of therapy with
Taxol and immunotoxin. Methods: Groups of nude mice (n=5~10) implanted s.c.
with A431/K5 tumor cells, expressing mesothelin and not ÉøvÉ¿3, were treated
with Taxol alone i.p. at 50 mg/kg on day 0 or mesothelin-specific immunotoxin SS1P alone i.v at 0.2 mg/kg on days 0 and 2. The tumor size was ~100 mm3 on day 0 and was measured daily. For the assessment of therapeutic response, the mice received i.v. the radiolabel (2.0 É Ci/<0.1 É g) in 0.2 ml of PBS with 1% BSA on days 1 and 4 for the Taxol alone groups and on days 1and 3 for the immunotoxin alone groups, and were euthanized at 1 or 2 hr post-injection for biodistribution.
Results: Each agent at the above doses maintained the tumor size unchanged during the course of therapy that enabled us to reliably measure the receptor density. Compared to the control without the drug treatment, the receptor uptake (% ID/g of tumor) of the radiolabel decreased by 22% on day 1 but increased by 49% on day 4, 2 days before rebounding of tumor growth, for the Taxol treated animals.
Comparatively, the uptake increased by 13% on day 1 and by 55% on day 3 for
the immunotoxin treated animals. The elevated receptor uptake on day 4 for
the Taxol and on day 3 for the 2 x SS1P treatment were statistically different from the control (p<0.01). Conclusions: The drastic increase of the receptor uptake prior to the rebound of tumor size suggests that the increase of angiogenic vessels precedes the re-growth of tumors and thus, addition of anti-angiogenic therapy may be beneficial.
|
|
