FLT-PET Imaging of Radiation Responses in Murine Tumors

Pan, Michael; Huang, Siyuan; Liao, Yu‐Pei; Schaue, Dörthe; Wang, C. C.; Stout, David; Barrio, Jorge R.; McBride, William H.

doi:10.1007/s11307-008-0158-z

Cited by 25 publications

(27 citation statements)

References 29 publications

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“…Cells in the G2 and M phases are about three times more sensitive than cells in the S phase. Following irradiation, the mammalian cell cycle halts in the G1 and/or G2M phase and is delayed in the S phase [15,31]. A stopped or delayed mitotic division due to the G2M phase arrest and a prolonged cycling time may lead to suppression of tumor growth.…”

Section: Discussionmentioning

confidence: 99%

“…However, 18 F-FDG highly accumulates in inflammatory lesions [33] and radiotherapy causes acute inflammation. Therefore, 18 F-FDG PET is often not applicable to monitoring the early tumor responses to radiotherapy [15,31]. On the other hand, several studies demonstrated that FLT-PET can noninvasively predict early tumor responses to radiotherapy [15,18,21].…”

Section: Discussionmentioning

confidence: 99%

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Monitoring tumor proliferative response to radiotherapy using 18F-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67

et al. 2013

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Objective Although radiotherapy is an important treatment strategy for head and neck cancers, it induces tumor repopulation which adversely affects therapeutic outcome. In this regard, fractionated radiotherapy is widely applied to prevent tumor repopulation. Evaluation of tumor proliferative activity using 18 F-fluorothymidine (FLT), a noninvasive marker of tumor proliferation, may be useful for determining the optimal timing of and dose in the repetitive irradiation. Thus, to assess the potentials of FLT, we evaluated the sequential changes in intratumoral proliferative activity in head and neck cancer xenografts (FaDu) using FLT. MethodsFaDu tumor xenografts were established in nude mice and assigned to control and two radiation-treated groups (10 and 20 Gy). Tumor volume was measured daily. 3 H-FLT was injected intravenously 2 hrs before sacrifice. Mice were sacrificed 6, 24, 48 hrs, and 7 days after the radiation treatment. Intratumoral 3 H-FLT level was visually and quantitatively assessed by autoradiography. Ki-67 immunohistochemistry (IHC) was performed. ResultsIn radiation-treated mice, the tumor growth was significantly suppressed compared with the control group, but the tumor volume in these mice gradually increased with time. In the visual assessment, intratumoral 3 H-FLT level diffusely decreased 6 hrs after the radiation treatment and then gradually increased with time, whereas no apparent changes were observed in Ki-67 IHC. Six hours after the radiation treatment at 10 and 20 Gy, the intratumoral 3 H-FLT level markedly decreased to 45 and 40% of the control, respectively (P < 0.0001, vs control), and 4 then gradually increased with time. In each radiation-treated group, the 3 H-FLT levels at 48 hrs and on day 7 were significantly higher than that at 6 hrs. The Intratumoral 3 H-FLT levels in both treated groups were 68 and 60% at 24 hrs (P < 0.001), 71 and 77% at 48 hrs (P < 0.001), and 83and 81% on day 7 (P = NS) compared with the control group.Conclusion Intratumoral FLT uptake level markedly decreased at 6 hrs and then gradually increased with time. Sequential evaluation of intratumoral proliferative activity using FLT can be beneficial for determining the optimal timing of and dose in repetitive irradiation of head and neck cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Monitoring tumor proliferative response to radiotherapy using 18F-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67

et al. 2013

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“…In biomedical animal imaging researches, murine is the most common animal species [18,19]. They have a variety of sizes, and the common fields-of-view (FOVs) are usually set as 3 cm for mouse and 5 cm for rat, respectively [20,21].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a Multi-pinhole Collimator for Imaging Small Animals with Different Sizes

Mok

et al. 2011

Mol Imaging Biol

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“…18 F] fluoro-2-deoxy-D-glucose (FDG) or 99mTc-bisphosphonate to detect metastases (8). Doppler ultrasonography is not an emerging method, but it is highly regarded by researchers.…”

Section: Introductionmentioning

confidence: 99%

Establishment of reproducible osteosarcoma rat model using orthotopic implantation technique

Sun²,

Fan³

et al. 2009

Oncol Rep

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Abstract. In experimental musculoskeletal oncology, there remains a need for animal models that can be used to assess the efficacy of new and innovative treatment methodologies for bone tumors. Rat plays a very important role in the bone field especially in the evaluation of metabolic bone diseases. The objective of this study was to develop a rat osteosarcoma model for evaluation of new surgical and molecular methods of treatment for extremity sarcoma. One hundred male SD rats weighing 125.45±8.19 g were divided into 5 groups and anesthetized intraperitoneally with 10% chloral hydrate. Orthotopic implantation models of rat osteosarcoma were performed by injecting directly into the SD rat femur with a needle for inoculation with SD tumor cells. In the first step of the experiment, 2x10 5 to 1x10 6 UMR106 cells in 50 μl were injected intraosseously into median or distal part of the femoral shaft and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from ultrasound with findings from necropsia and determining time of survival. In the third stage, the orthotopically implanted tumors and lung nodules were resected entirely, sectioned, and then counter stained with hematoxylin and eosin for histopathologic evaluation. The tumor take rate was 100% for implants with 8x10 5 tumor cells or more, which was much less than the amount required for subcutaneous implantation, with a high lung metastasis rate of 93.0%. Ultrasound and necropsia findings matched closely (r=0.942; p<0.01), which demonstrated that Doppler ultrasonography is a convenient and reliable technique for measuring cancer at any stage. Tumor growth curve showed that orthotopically implanted tumors expanded vigorously with time-lapse, especially in the first 3 weeks. The median time of survival was 38 days and surgical mortality was 0%. The UMR106 cell line has strong carcinogenic capability and high lung metastasis frequency. The present rat osteosarcoma model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. It may be a useful tool in the investigation of antiangiogenic and anticancer therapeutics. Ultrasound was found to be a highly accurate tool for tumor diagnosis, localization and measure-ment and may be recommended for monitoring tumor growth in this model.

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FLT-PET Imaging of Radiation Responses in Murine Tumors

Cited by 25 publications

References 29 publications

Monitoring tumor proliferative response to radiotherapy using 18F-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67

Monitoring tumor proliferative response to radiotherapy using 18F-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67

Evaluation of a Multi-pinhole Collimator for Imaging Small Animals with Different Sizes

Establishment of reproducible osteosarcoma rat model using orthotopic implantation technique

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