Av. Kirichenko et al., Nuclear scintigraphic assessment of intestinal dysfunction after combined treatment with 9-amino-20(S)-camptothecin (9-AC) and irradiation, INT J RAD O, 47(4), 2000, pp. 1043-1049
Citations number
32
Categorie Soggetti
Radiology ,Nuclear Medicine & Imaging","Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
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.