Rennen Huub J J M, Laverman Peter, van Eerd Julliëtte E M, Oyen Wim J G, Corstens Frans H M, Boerman Otto C
Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Nucl Med Biol. 2007 Aug;34(6):691-5. doi: 10.1016/j.nucmedbio.2007.04.012. Epub 2007 Jul 5.
It was previously shown that the (99m)Tc-labeled hydrazinonicotinamide (HYNIC)-conjugated LTB4 antagonist MB81 visualized infectious foci in rabbits adequately and within a few hours after injection. Here, the bivalent HYNIC-conjugated LTB4 antagonist MB67 (analog of MB81) was fluorinated with (18)F via hydrazone formation and tested in vivo.
MB67 was [(18)F]-fluorinated via reaction of the [(18)F]-fluorinated intermediate p-[(18)F]-fluorobenzaldehyde ([(18)F]FB) and the HYNIC moiety of MB67 via hydrazone formation. For comparison, MB67 was also labeled with (99m)Tc. The biodistribution of (18)F- and (99m)Tc-labeled MB67 was investigated in rabbits with intramuscular infection.
[(18)F]-MB67 was obtained at a maximum specific activity of 1200 GBq/mmol and proved to be stable in phosphate buffered saline (PBS) at 37 degrees C for at least 4 h. PET images obtained with [(18)F]-MB67 clearly delineated the abscess at 2 and 4 h pi. Counting of dissected tissues at 4 h pi revealed an abscess uptake of 0.073+/-0.005 %ID/g, as compared to 0.160+/-0.010 %ID/g for the (99m)Tc-labeled analog. Abscess-to-muscle ratios were 23+/-4 for [(18)F]-MB67 and 35+/-9 for [(99m)Tc]-MB67.
The present study showed the feasibility of a new [(18)F]-labeling methodology and its application in the production of a new PET tracer for imaging of infection, [(18)F]-MB67.
先前的研究表明，（99m）Tc标记的肼基烟酰胺（HYNIC）偶联的白三烯B4拮抗剂MB81在注射后数小时内就能很好地显示兔体内的感染灶。在此，二价HYNIC偶联的白三烯B4拮抗剂MB67（MB81的类似物）通过腙形成用（18）F进行氟化并在体内进行测试。
MB67通过（18）F标记的中间体对-[(18)F]-氟苯甲醛（[(18)F]FB）与MB67的HYNIC部分通过腙形成反应进行[(18)F]氟化。为作比较，MB67也用（99m）Tc进行标记。在患有肌肉感染的兔中研究了（18）F和（99m）Tc标记的MB67的生物分布。
获得了比活度最高为1200 GBq/mmol的[(18)F]-MB67，并且证明其在37℃的磷酸盐缓冲盐水（PBS）中至少4小时稳定。用[(18)F]-MB67获得的PET图像在注射后2小时和4小时清晰地勾勒出脓肿。注射后4小时对解剖组织的计数显示脓肿摄取为0.073±0.005 %ID/g，而（99m）Tc标记的类似物为0.160±0.010 %ID/g。[(18)F]-MB67的脓肿与肌肉的比值为23±4，[(99m)Tc]-MB67为35±9。
本研究表明了一种新的[(18)F]标记方法的可行性及其在生产用于感染成像的新型PET示踪剂[(18)F]-MB67中的应用。
