| Abstract: | Little is known about drug distribution in tumor metastases or in the liver after hepatic arterial infusion. This information is important for planning strategies to enhance tumor drug uptake and to improve tumor response to therapy. Dye injection studies have demonstrated hepatic tumor vascular supplies in an anatomic manner, but offer no physiologic data. To evaluate hepatic drug distribution in patients with metastases to the liver and colon and rectum (6-3H) 5-fluorodeoxyuridine (FUdR) and 99m-technetium (TC) macroaggregated albumin (MAA) were infused through the hepatic artery prior to lobectomy of the right hepatic lobe in three patients and before wedge resection of a metastasis in one patient. Forty to 100 specimens of the tumor and liver taken at biopsy were assayed in order to map drug and albumin distribution. Nuclide scanning of the specimen was performed upon two patients. A linear relationship between levels of 3H (representing fluoropyrimidine metabolites) and 99mTc (representing blood flow) was demonstrated in both the tumor (correlation coefficients 0.69 to 0.87, p less than 0.01) and liver (correlation coefficients 0.76 to 0.90, p less than 0.001). The liver immediately adjacent to the tumor retained substantially more 99mTc-MAA than either the tumor itself or liver remote from the tumor, as demonstrated by both nuclide scanning and tissue biopsies. The rim of the liver adjacent to the tumor with enhanced 99mTc uptake had a different histologic appearance from a "normal" liver at a distance from the tumor in all instances. A radionuclide hepatic scan showing increased tumor uptake of 99mTc-MAA after arterial injection predicts an increased likelihood of tumor response to treatment. The results of this study demonstrate for the first time, in human beings, that increased 3H-FUdR uptake occurs in portions of the tumor which retain more 99mTc-MAA and explains the capacity of the arterial 99mTc-MAA perfusion scan to predict tumor response in the treatment of metastases to the liver and colon and rectum. |
