Nuclear scintigraphic assessment of intestinal dysfunction after combined treatment with 9-amino-20(S)-camptothecin (9-AC) and irradiation

Purpose: The camptothecins (CPTs) are potent radiosensitizers of malignant tumors in vivo, The extent of normal tissue damage after combined CPT and r adiation treatment is unknown, In this article, a jejunal absorption assay with Tc-99m. pertechnetate (Na[(TcO4)-Tc-99m]) was used to assess C3H/Kam m ice given total body irradiation (TBI) of 4 Gy, 6 Gy, and 8 Gy, 2 mg/kg sin gle intramuscular injection of 9-AC or a combination of 2 mg/kg 9-AC + 4 Gy TBI, We also correlated the absorption data with morphologic changes in th e jejunal mucosa, Materials and Methods: ((TcO4)-Tc-99m)(-) absorption from the intestinal lu men into the circulation was studied with dynamic gamma-scintigraphy combin ed with a multichannel analyzer to record the radiometry data in a time-dep endent fashion. Jejunal cross sections were scored for the number of cells per villus and the percentage of apoptotic and mitotic cells in the crypt c ompartment, The jejunal microcolony assay was used to quantify jejunal cryp t survival Results: A dose-dependent decrease in the absorption function was observed 3.5 days following TBI, The mean absorption rate was reduced to 89 +/- 16% of control in response to a sublethal 4 Gy TBI and dropped to 47.5 (9.8% in response to 8 Gy TBI, The mean rate of intestinal absorption was delayed b y single sublethal 2 mg/kg 9-AC injection to 62 (11% in comparison with con trol values. The combination of a single 4 Gy TBI with a 9-AC treatment dec reased the ((TcO4)-Tc-99m)- jejunal absorption in an additive fashion produ cing absorption lifetime values more than twofold longer than controls. The decrease in ((TcO4)-Tc-99m)- absorption at 3.5 days after irradiation, 9-A C treatment or the combination of the two agents correlates with the number of cells per villus and the percentage of apoptotic cells in the crypt com partment. Conclusion: Dynamic enteroscintigraphy with Tc-99m-pertechnetate is a sensi tive functional assay for rapid evaluation of radiation and chemotherapy in duced intestinal damage. Reduced intestinal absorptive function has a cellu lar basis and correlates directly with the numbers of cells lost per villus in a treatment-dependent manner, (C) 2000 Elsevier Science Inc.