Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
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Feasibility of Reflecting Improvement of Tumor Hypoxia by Mild Hyperthermia in Experimental Mouse Tumors with $^18F-Fluoromisonidazole$

저온온열치료에 의한 종양 내 저산소상태 개선효과를 $^18F$-Fluoromisonidazole의 섭취 변화를 이용한 평가

  • Lee Sang-wook (Departments of Radiation Oncology,Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Ryu Jin Sook (Departments of Nuclear Medicine, Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Oh Seung Joon (Departments of Nuclear Medicine, Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Im Ki Chun (Departments of Nuclear Medicine, Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Chen Gi Jeong (Departments of Nuclear Medicine, korea Institute of Radiological and Medical Sciences) ;
  • Lee So Ryung (Departments of Radiation Oncology,Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Song Do Young (Departments of Radiation Oncology,Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Im Soo Jeong (Departments of Nuclear Medicine, Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Moon Eun Sook (Departments of Radiation Oncology,Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Kim Jong Hoon (Departments of Radiation Oncology, Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Ahn Seung Do (Departments of Radiation Oncology,Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Shin Seong Soo (Departments of Radiation Oncology,Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Lee Kyeong Ryong (Department of Emergency Medical, Konkuk University)
  • 이상욱 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 류진숙 (울산대학교 의과대학 서울아산병원 핵의학과) ;
  • 오승준 (울산대학교 의과대학 서울아산병원 핵의학과) ;
  • 임기천 (울산대학교 의과대학 서울아산병원 핵의학과) ;
  • 천기정 (원자력병원 핵의학과, 방사선의학연구센터) ;
  • 이소령 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 송도영 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 임수정 (울산대학교 의과대학 서울아산병원 핵의학과) ;
  • 문은숙 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 김종훈 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 안승도 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 신성수 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 이경룡 (건국대학교병원 응급의학과)
  • Published : 2004.12.01
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Abstract

Puporse: The aims of this study were to evaluate the change of $[^18F]fluoromisonidazole$($[^18F]FMISO$) uptake in C3H mouse squamous cell carcinoma-VII (SCC-VII) treated with mild hyperthermia ($42^{circ}C$) and nicotinamide and to assess the biodistribution of the markers in normal tissues under similar conditions. Methods and Materials: $[^18F]FMISO$ was producedby our hospital. Female C3H mice with a C3H SCC-VII tumor grown on their extremities were used. Tumors were size matched. Non-anaesthetized, tumor-bearing mice underwent control or mild hyperthermia at $42^{circ}C$ for 60 min with nicotinamide (50 mg/kg i.p. injected) and were examined by gamma counter, autoradiography and animal PET scan 3 hours after tracer i.v. injected with breathing room air, The biodistribution of these agents were obtained at 3 h after $[^18F]FMISO$ injection. Blood, tumor, muscle, heart, lung, liver, kidney, brain, bone, spleen, and intestine were removed, counted for radioactivity and weighed. The tumor and liver were frozen and cut with a cryomicrotome into 10- um sections. The spatial distribution of radioactivity from the tissue sections was determined with digital autoradiography. Results: The mild hyperthermia with nicotinamide treatment had only slight effects on the biodistribution of either marker in normal tissues. We observed that the whole tumor radioactivity uptake ratios were higher in the control mice than in the mild hyperthermia with nicotinamide treated mice for $[^18F]FMISO$ ($1.56{\pm}1.03$ vs. $0.67{\pm}0.30$; p=0.063). In addition, autoradiography and animal PET scan demonstrated that the area and intensity of $[^18F]FMISO$ uptake was significantly decreased. Conclusion: Mild hyperthermla and nicotinamide significantly improved tumor hypoxia using $[^18F]FMISO$ and this uptake reflected tumor hypoxic status.

목적: 종양 내에서 산소공급 부족현상으로 발생하는 저산소증 조직에서 저온온열치료($42^{circ}C$)와 nicotinamide에 의한 perfusion limited 저산소증의 개선 효과를 마우스 종양 모델을 이용하여 종양 내 $[^18F]FMISO$ 섭취변화를 이용하여 증명할 수 있는지 알아보고자 하였다. 대상 및 방법: C3H 마우스에 $[^18F]FMISO$를 정주하고 11개 장기에서 $\%ID/g$을 구하여 biodistribution을 관찰하였다. 또한 같은 마우스에 동종 종양세포인 SCC7을 이식하여 종양모델을 만들고 저온온열치료($42^{circ}C$)와 nico-tinamide를 투여한 마우스와 대조군 마우스에서 $[^18F]FMISO$의 섭취정도 차이를 $\%ID/g$, autoradiography, PET scan을 시행하여 비교하고자 하였다. 결과: 대조군에서 종양의 FMISO의 섭취는 5.1+/-2.28 $\%ID/g$였고, 종양/근육, 종양/혈액의 섭취비는 2.2와 1.8이었다. 실험군에서는 각각 2.4+/-0.64 $\%ID/g$, 1.4와 1.2를 나타내어 대조군보다 유의하게 낮았다(p<0.021). Autoradiography에서 대조군의 종양 내부에 FMISO가 섭취됨을 확인하였고, 저온온열치료와 nico-tinamide를 투여한 실험군에서는 섭취가 감소된 것을 관찰하였다. 결론: C3H 마우스와 동종 종양세포인 SCC-VII을 이용한 종양모델에서 $[^18F]FMISO$가 종양내에 섭취가 되어 자산소증 종양모델로 적절함을 확인하였고, 저온온열치료($42^{circ}C$)와 nicotinamide에 의한 perfusion limited 저산소증 개선효과를 $[^18F]FMISO$의 종양 내 섭취가 감소하는 것을 통하여 확인할 수 있었다.

Keywords

References

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