Evaluation of cellular uptake, tumor retention, radiation response, and tumor pathophysiology in experimental solid tumors after an intratumoral infusion of colloidal 32P.

Abstract

Order et al. successfully deposited > 85% of radionuclides in pancreatic carcinoma patients using an intratumoral (i. t.) infusion of macroaggregated albumin (MAA) prior to the i. t. infusion of colloidal 32P (32P-CP), apparently due to MAA-induced transient blockade. However, no studies regarding physiologic response and the inhibitory tumor growth of solid tumors after treatment with 32P-CP with or without MAA have been performed. First, the authors determined the cellular uptake of 32P-CP in 10 cell lines. They then evaluated the relationship between tumor retention and radiation response in vivo. Third, they evaluated the changes in physiologic parameters such as tumor interstitial fluid pressure (TIFP) and tumor blood flow (TBF) after an i. t. infusion of MAA. In the plateau growth phase of both H4IIE and LS174T tumors, maximal uptake occurred at approximately 100 minutes after treatment with 10 microCi of 32P-CP, but uptake in LS174T was approximately 2 times higher than that in H4IIE. In animal experiments, 32P-CP alone significantly inhibited the tumor growth of H4IIE. However, additional i. t. infusion of MAA did not improve the growth delay induced by 32P-CP, mainly due to insignificant differences in retention of radioactivity when using 32P-CP with or without MAA. It was speculated that when the outflow of the tumor vasculature was obstructed by clamping (or an i. t. infusion of MAA), it would reduce TBF and increase TIFP. However, neither increased TIFP nor decreased TBF was observed when MAA was given i. t. to tumors. The authors concluded that an MAA-induced transient blockade of tumor vasculature after an i. t. infusion of MAA did not occur in experimental solid tumors.