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Nuklearmedizin 2011; 50(06): 234-239
DOI: 10.3413/Nukmed-0349-10-09
Original article
Schattauer GmbH

Rhenium-188 labeled recombinant human plasminogen kringle5 (rhk5) and preliminary biodistribution

Evaluation in mice bearing A549 tumoursRhenium-188 markiertes, rekombinantes humanes Plasminogen Kringle 5 (rhk5) und vorläufige BioverteilungBeurteilung bei Mäusen mit A549-Tumoren
R. Guo
1   Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, PR China
,
Y. Ma
2   Shanghai Institute of Applied Physics (SINAP), Chinese Academy of Sciences, Shanghai, PR China
,
R. Zhang
3   Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, PR China
,
S. Liang
1   Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, PR China
,
H. Shen
2   Shanghai Institute of Applied Physics (SINAP), Chinese Academy of Sciences, Shanghai, PR China
,
H. Xu
1   Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, PR China
,
B. Li
1   Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, PR China
› Author Affiliations
Further Information

Publication History

received: 06 September 2010

accepted in revised form: 28 February 2011

Publication Date:
28 December 2017 (online)

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Summary

Aim: Angiogenesis plays a critical role in tumour formation and metastasis. Suitable radiolabeled angiogenesis inhibitor can be used for noninvasive imaging of angiogenesis and radionuclide therapy. Here we prepare rhenium-188 labeled recombinant human plasminogen kringle5 (188Re-rhk5) in a convenient manner than evaluate its properties in A549 lung adenocarcinoma. Methods: 188Rerhk5 was obtained by conjugating His group at the C end of rhk5 with fac- [188Re(H2O)3(CO)3]+. Chelating efficiency of fac-[188Re(H2O)3(CO)3]+ and radiolabeling efficiency of 188Re-rhk5 were measured by radio thin-layer chromatography (RTLC). In vitro stability of 188Re-rhk5 was determined in human serum at 37°C and analyzed by RTLC. Competition test was also performed to verify the specificity of binding. A biodistribution study was carried out in nude mice bearing A549 lung adenocarcinoma. Results: 188Rerhk5 was obtained with a radiolabel efficiency of 66.1%, the radiochemical purity (RCP) can marreach 95.2% after purification. 188Re-rhk5 showed high stability in human serum, the RCP was more than 80% even 12 h after incubation. Competition test showed a high binding specificity. Furthermore, this radio-complex was excreted mainly through kidneys and showed specific tumour uptake in mice bearing A549 tumours. Conclusion: 188Re-rhk5 was prepared by a simple method. Preliminary biodistribution results showed its potential as an agent for possible tumour imaging, therapy and encouraged further investigation.

Zusammenfassung

Ziel: Die Angiogenese spielt bei der Entstehung von Tumoren und Metastasen eine entscheidende Rolle. Für die nicht invasive Darstellung der Angiogenese und die Radionuklidtherapie können geeignete radioaktiv markierte Angiogenese- Inhibitoren verwendet werden. Wir stellen auf einfache Weise Rhenium-188 markiertes, rekombinantes humanes Plasminogen Kringle 5 (188Re-rhk5) her und untersuchen seine Eigenschaften an A549-Adenokarzinomen der Lunge. Methoden: Die Konjugation der C-terminalen His-Gruppe von rhk5 mit fac-[188Re(H2O)3(CO)3]+ ergab 188Rerhk5. Die Wirksamkeit von fac- [188Re(H2O)3(CO)3]+ als Chelatbildner und die von 188Re-rhk5 als radioaktiver Marker wurden mittels Radiodünnschichtchromatographie (RTLC) bestimmt. Die In-vitro-Stabilität von 188Re-rhk5 wurde in menschlichem Serum bei 37°C bestimmt und mittels RTLC untersucht. Außerdem wurden kompetitive Tests durchgeführt, um die Bindungsspezifität zu verifizieren. Die Untersuchung der Bioverteilung erfolgte mithilfe von Nachtmäusen mit pulmonalen A549-Adenokarzinomen. Ergebnisse: Die Wirksamkeit von 188Re-rhk5 als radioaktiver Marker betrug 66,1%, nach Purifikation kann eine radiochemische Reinheit (RCP) von 95,2% erreicht werden. 188Re-rhk5 erwies sich in menschlichem Serum als sehr stabil, noch 12 h nach Inkubation lag die RCP bei über 80%. Die kompetitive Testung ergab eine hohe Bindungsspezifität. Des Weiteren wurde dieser radioaktive Komplex überwiegend renal ausgeschieden und bei Mäusen mit A549-Tumoren spezifisch in Tumore aufgenommen. Schlussfolgerung: 188Re-rhk5 wurde nach einer einfachen Methode hergestellt. Vorläufige Ergebnisse zur Bioverteilung zeigen sein Potenzial für den Einsatz bei der Tumorbildgebung und -therapie sowie bei weiteren Untersuchungen.

Keywords

188Re - kringle5 - tumour - angiogenesis - label

Schlüsselwörter

188Re - Kringle 5 - Tumor - Angiogenese - Markierung
 

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