Small Animal PET Imaging Study of 68Ga-BAPEN

68Ga-BAPEN 소동물 PET영상 연구

  • Kim, Ji-Who (Department of Nuclear Medicine, Interdisciplinary Program in Radiation Applied Life Science, Seoul National University) ;
  • Lee, Jae-Sung (Department of Nuclear Medicine, Interdisciplinary Program in Radiation Applied Life Science, Seoul National University) ;
  • Yang, Bo-Yeun (Department of Nuclear Medicine, Interdisciplinary Program in Radiation Applied Life Science, Seoul National University) ;
  • Kim, Su-Jin (Department of Nuclear Medicine, Interdisciplinary Program in Radiation Applied Life Science, Seoul National University) ;
  • Kim, Joong-Hyun (Department of Nuclear Medicine, Interdisciplinary Program in Radiation Applied Life Science, Seoul National University) ;
  • Jeong, Jae-Min (Department of Nuclear Medicine, Interdisciplinary Program in Radiation Applied Life Science, Seoul National University) ;
  • Lee, Dong-Soo (Department of Nuclear Medicine, Interdisciplinary Program in Radiation Applied Life Science, Seoul National University)
  • 김지후 (서울대학교 의과대학 핵의학교실, 협동과정 방사선응용생명과학) ;
  • 이재성 (서울대학교 의과대학 핵의학교실, 협동과정 방사선응용생명과학) ;
  • 양보연 (서울대학교 의과대학 핵의학교실, 협동과정 방사선응용생명과학) ;
  • 김수진 (서울대학교 의과대학 핵의학교실, 협동과정 방사선응용생명과학) ;
  • 김중현 (서울대학교 의과대학 핵의학교실, 협동과정 방사선응용생명과학) ;
  • 정재민 (서울대학교 의과대학 핵의학교실, 협동과정 방사선응용생명과학) ;
  • 이동수 (서울대학교 의과대학 핵의학교실, 협동과정 방사선응용생명과학)
  • Received : 2011.09.28
  • Accepted : 2011.12.01
  • Published : 2011.12.30

Abstract

The purpose of this study was to analyze $^{68}Ga$-BAPEN dynamic PET image in rat myocardium to evaluate potential of this radiotracer as a perfusion imaging agent. Animal PET/CT scan was done in 9 rats during 120 minutes. Especially we synthesized $^{68}Ga$-BAPEN with kit which is simple and low cost method. PET images showed the in vivo dynamic distribution of $^{68}Ga$-BAPEN in the chest region of rats. Initially $^{68}Ga$-BAPEN PET images showed aorta and liver activities and a few minutes later, $^{68}Ga$-BAPEN moved to myocardium. Regions of interest were drawn on myocardium, liver, lung and blood pool. Time-activity curves showed significant uptake of $^{68}Ga$-BAPEN in myocardium. The contrast ratios of myocardial to blood pool, lung and liver at 60 minutes after injection were 1.66, 2.82 and 0.60. To estimate accurate kinetic parameters, 60 minutes after injection was required to PET scan as myocardium image contrast ratios reached to constant values. As a result, $^{68}Ga$-BAPEN would be suitable radiotracer for PET which can applied to diagnosis of myocardial perfusion diseases after further preclinical and clinical investigations.

본 연구에서는 소동물의 심근에서 $^{68}Ga$-BAPEN PET 영상분석을 통해 심혈 영상 추적자로서의 적용가능성을 보고자 하였다. 소동물용 PET/CT에서 쥐 9마리를 대상으로 120분간의 $^{68}Ga$-BAPEN PET/CT 스캔을 시행하였다. 특별히 킷트를 통해 간편하고 저비용으로 $^{68}Ga$-BAPEN을 합성이 가능하였다. PET 영상은 쥐의 몸통부분에서 $^{68}Ga$-BAPEN의 생체 동적분포를 나타낸다. $^{68}Ga$-BAPEN PET 영상은 처음 수분간 대동맥과 간에서의 섭취가 나타났고 점차 심근에서의 섭취가 이루어졌다. 관심영역은 좌심근, 심혈, 폐, 간에 그렸고 시간-방사능 곡선을 얻었다. 시간-방사능 곡선에서 $^{68}Ga$-BAPEN이 쥐 심근에 잘 결합하는 것을 확인 할 수 있었다. 정확한 약동학적 파라미터 도출을 위한 최소 PET 스캔시간은 타장 기와의 영상 대조도가 일정비에 이르는 주사 후 60분이 적합하였다. 이때 심근의 섭취를 심혈, 간, 폐에서의 섭취로 나누어 얻은 영상 대조도는 각각 1.66, 0.60, 2.82였다. 결론적으로 $^{68}Ga$-BAPEN은 심근 혈류 질환을 진단하기 위한 추적자로서 적합하며 지속적인 연구가 이루어진다면 임상에서의 진단활용에 도움이 될 것이라 예상된다.

Keywords

References

  1. Schwaiger M, Muzik O: Assessment of myocardial perfusion by positron emission tomography. Am J Cardiol 67:35D-43D (1991) https://doi.org/10.1016/S0002-9149(05)80006-2
  2. Degrado TR, Bergmann SR, Ng CK, Raffel DM: Tracer kinetic modeling in nuclear cardiology. J Nucl Cardiol 7:686-700 (2000) https://doi.org/10.1067/mnc.2000.111127
  3. Camici PG: Positron emission tomography and myocardial imaging. Heart 83:475-480 (2000) https://doi.org/10.1136/heart.83.4.475
  4. Croteau E, Benard F, Bentourkia M, Rousseau J, Paquette M, Lecomte R: Quantitative myocardial perfusion and coronary reserve in rats with $^{13}N-ammonia$ and small animal PET: impact of anesthesia and pharmacologic stress agents. J Nucl Med 45:1924-1930 (2004)
  5. Nekolla SG, Reder S, Saraste A, et al: Evaluation of the novel myocardial perfusion positron-emission tomography tracer $^{18}F$-BMS-77158-02. comparison to $^{13}N-ammonia$ and validation with microsphere in a pig model. Circulation 119:2333-2342(2009) https://doi.org/10.1161/CIRCULATIONAHA.108.797761
  6. Higuchi T, Nekolla SG, Huisman MM, et al: A new $^{18}F-labeled$ myocardial PET tracer: myocardial uptake after permanent and transient coronary occlusion in rats. J Nucl Med 49:1715-1722 (2008) https://doi.org/10.2967/jnumed.108.053967
  7. Go RT, Marwick TH, Maclntyre WJ, et al: A prospective comparison of Rubidium-82 PET and Thallium-201 SPECT myocardial perfusion imaging utilizing a single dipyridamole stress in the diagnosis of coronary artery disease. J NucI Med 31: 1899-1905 (1990)
  8. Choi Y, Huang SC, Hawkins RA, et al: Quantification of myocardial blood flow using $^{13}N-ammonia$ and PET: comparison of tracer models. J Nucl Med 40:1045-1055 (1999)
  9. Lortie M, Beanlands RS, Yoshinaga K, Klein R, Dasilva JN, DeKemp RA: Quantification of myocardial blood flow with $^{82}Rb$ dynamic PET imaging. Eur J Nucl Med Mol Imaging 34:1765-1774 (2007) https://doi.org/10.1007/s00259-007-0478-2
  10. Klein R, Renaud JM, Ziadi MC, et al: Intra- and inter- operator repeatability of myocardial blood flow and myocardial flow reserve measurements using Rubidium-82 PET and a highly automated analysis program. J Nucl Cardiol 17: 600-616 (2010) https://doi.org/10.1007/s12350-010-9225-3
  11. Eisner R, Churchwell A, Noever T, et al: Quantitative analysis of the tomographie Thallium-201 myocardial bullseye display critical role of correcting for patient motion. J Nucl Med 29:92-97 (1988)
  12. EL Fakhri G, Kardan A, Sitek A, et al: Reproducibility and accuracy of quantitative myocardial blood flow assessment with $^{82}Rb$ PET: comparison with $^{13}N-ammonia$ PET. J Nucl Med 50:1062-1071 (2009) https://doi.org/10.2967/jnumed.104.007831
  13. Tsang BW, Mathias CJ, Green MA: A Gallium-68 radiopharmaceutical that is retained in myocardium: $^{68}Gal[(4,6-MeO_2sal)_2BAPEN]^+$. J Nucl Med 34:1127-1131 (1993)
  14. Nitzsche EU, Choi Y, Czemin J, Hoh CK, Huang SC, Schelbert HR: Noninvasive quantification of myocardial blood flow in humans: a direct comparison of the $[^{13}N]ammonia$ and the $[^{15}O]water$ techniques. Circulation 93:2000-2006 (1996) https://doi.org/10.1161/01.CIR.93.11.2000
  15. Lee JS, Lee DS, Ahn JY, et al: Parametric image of myocardial blood flow generated from dynamic $H_2^{15}O$ PET using factor analysis and cluster analysis. Med Biol Eng Comput 43:678-685 (2005) https://doi.org/10.1007/BF02351043
  16. Ahn JY, Lee DS, Lee JS, et al: Quantification of regional myocardial blood flow using dynamic $H_2^{15}O$ PET and factor analysis. J Nucl Med 42:782-787 (2001)
  17. Lee JS, Lee DS, Ahn JY, et al: Blind separation of cardiac components and extraction of input function from $H_2^{15}O$ dynamic myocardial PET using independent component analysis. J Nucl Med 42:938-943 (2001)
  18. Lee JS, Lee DS, Ahn JY, et al: Generation of parametric image of regional myocardial blood flow using $H_2^{15}O$ dynamic PET and a linear least-squares method. J Nucl Med 46:1687-1695 (2005)
  19. Hsiao YM, Mathias CJ, Wey SP, Fanwick PE, Green MA: Synthesis and biodistribution of lipophilic and monocationic gallium radiophramceuticals derived from N, N'-bis(3-aminopropyl)- N, N'-dimethylethylenediamine: potential agents for PET myocardial Imaging with $^{68}Ga$. Nucl Med Biol 36:39-45 (2008)
  20. Yang BY, Jeong JM, Kim YJ, et al: Formulation of $^{68}Ga$ BAPEN kit for myocardial positron emission tomography Imaging and biodistribution study. Nucl Med Biol 37:149-155 (2010) https://doi.org/10.1016/j.nucmedbio.2009.10.010
  21. Lee JS, Park KS, Lee DS, Lee CW, Chung JK, Lee MC: Development and applications of a software for Functional Image Registration (FIRE). Comput Meth Prog Bio 78:157-164 (2005) https://doi.org/10.1016/j.cmpb.2004.12.007
  22. Muzik O, Beanlands RS, Hutchins GD, Mangner TJ, Nguyen N, Schwaiger M: Validation of nitrogen-13-ammonia tracer kinetic model for quantification of myocardial blood flow using PET. J Nucl Med 34:83-91 (1993)
  23. Iida H, Rhodes CG, de Silva R, et al: Myocardial tissue fraction-correction for partial volume effects and measure of tissue viability. J Nucl Med 32:2169-2175 (1991)
  24. Carvalho PA, Chiu ML, Kronauge JF, et al: Subcellular distribution and analysis of technetium-99m-MIBI in isolated perfused rat hearts. J Nucl Med 33:1516-1522 (1992)
  25. Crane P, Laliberté R, Heminway S, et al: Effect of mitochondrial viability and metabolism on technetium-99m-sestamibi myocardial retention. Eur J Nucl Med 20:20-25 (1993) https://doi.org/10.1007/BF02261241
  26. Wang J, Yang CT, Kim YS, et al: $^{64}Cu--Labeled$ triphenylphosphonium and triphenylarsonium cations as highly tumorselective imaging agents. J Med Chem 50:5057-5069 (2007) https://doi.org/10.1021/jm0704088