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The Distribution of [³H]Vinblastine in Tumor and Host Tissues of Nb Rats Bearing a Transplantable Lymphoma Which is Highly Sensitive to the Alkaloid¹

Cancer Research Centre, University of British Columbia, Vancouver, British Columbia, Canada V6T 1W5

A new transplantable lymphoma in Nb rats responded dramatically to treatment with vinblastine (VLB). A single i.p. injection of VLB, 0.8 mg/kg, caused even highly advanced tumors to regress until they were no longer palpable. For investigation of the hypothesis that the oncolytic response may reflect a special affinity of VLB for the tumor, lymphoma-bearing rats were given an i.p. injection of [³H]VLB, and the levels of radioactivity and [³H]VLB in the tumor and host tissues were determined as a function of time. Radioactivity was concentrated by the lymphoma relative to the blood (mostly as unchanged [³H]VLB) at levels that showed only a modest decline over a period of at least 48 hr. During this time the [³H]VLB in both the plasma and white blood cell fraction of the blood declined markedly and continuously to very low levels. Thymus and lymph nodes resembled the lymphoma in showing a long-term retention of radioactivity. The levels of radioactivity in the spleen, liver, and bone marrow were initially much higher than that in the tumor but decreased markedly with time. In addition very little of the radioactivity remaining in the spleen and liver at 48 hr was due to [³H]VLB, and by this time the VLB concentration in these tissues was much lower than in the tumor. It is suggested that the chemotherapeutic response of the lymphoma may be related to the continuing presence of a significant concentration of VLB in this tumor after the plasma VLB had fallen to very low (subantimitotic) levels.

¹ This study was supported by the National Cancer Institute of Canada and the Medical Research Council of Canada.

² Research Associate, Medical Research Council of Canada. To whom requests for reprints should be addressed.

Received 7/26/76. Accepted 2/14/77.