Monitoring of response to radiation therapy for human tumor xenografts using 99mTc-HL91 (4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime).
OBJECTIVE
Oxygenation status of tumor tissue is an important factor to discriminate it with respect to its radiosensitivity. 99mTc-4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime (99mTc-HL91) is retained in hypoxic tissues, making it possible to use it as hypoxic imaging agent. We evaluated if the accumulation of 99mTc-HL91 in tumors could aid in the prediction of sensitivity of radiation therapy of cancers.


METHODS
Human tumors (the gastric cancer cell line: MKN45, the epidermoid carcinoma cell line: KB-31, and the lung adenocarcinoma cell line: HLC) were xenografted into the thigh of athymic mice and irradiated with a 4 MV linear accelerator. Tumor growth was measured and 99mTc-HL91 uptakes in tumors were determined by serial imaging, biodistribution, and autoradiography.


RESULTS
99mTc-HL91 uptake (ratio of ROItumor to ROIwhole body) in HLC ranged from 1.1 to 8.0%, and it did not show any response to radiation therapy. Major variations were observed in 99mTc-HL91 accumulation in MKN45 and KB-31; from 0.7 to 4.7%, and from 1.0 to 7.3%, respectively. Some tumors responded to radiotherapy, while others did not. Tumor response was not dependent on the 99mTc-HL91 uptake, tumor size or radiation dose. Comparing 99mTc-HL91 uptake in tumors before (B) and after (A) their radiation, uptake (B) was always smaller than uptake (A) for HLC, and they did not respond to irradiation at all. For MKN45 and KB-31, tumors responded to radiation when their uptake (A) was not higher than uptake (B). In contrast, the tumors continued to grow when their uptake (A) was higher than uptake (B). Sequential 99mTc-HL91 imaging of KB-31 and their autoradiography indicated that tumors whose 99mTc-HL91 uptakes was increased post irradiation were composed of mainly hypoxic cells. On the other hand, many viable areas were observed in tumors when the increase in 99mTc-HL91 uptake was relatively small.


CONCLUSIONS
99mTc-HL91 uptake in tumors did not always relate to their sensitivities to radiation therapy. Sequential 99mTc-HL91 imagings post irradiation showed that the increase in 99mTc-HL91 uptake in tumors predicted a poor response to radiation therapy, and that a decrease or no change suggested that radiation therapy would be effective. Monitoring by 99mTc-HL91 imaging is a good tool to predict the radiosentivities of tumors.
Suzuki
Takayuki
T
Department of Radiology, Keio University School of Medicine, Tokyo, Japan. suzuten@ka2.so-net.ne.jp
Nakamura
Kayoko
K
Kawase
Takatsugu
T
Kubo
Atsushi
A
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D010091:Oximes / Q000493:pharmacokinetics*; D011836:Radiation Tolerance; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011879:Radiotherapy Dosage; D012983:Soft Tissue Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D013274:Stomach Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D015609:Organotechnetium Compounds; D010091:Oximes; D019275:Radiopharmaceuticals; C105527:technetium Tc 99m 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime