Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
권호 표지
DOI QR코드

DOI QR Code

Development of bombesin peptide kit for prostate cancer diagnosis and treatment using 64Cu/177Lu.

  • Kim, Mi Hyun (RI-Convergence Research, Korea Institute of Radiological and Medical Sciences) ;
  • Kim, Min Hwan (RI-Convergence Research, Korea Institute of Radiological and Medical Sciences) ;
  • Kim, Kwang Il (RI-Convergence Research, Korea Institute of Radiological and Medical Sciences) ;
  • Kim, Jung Young (RI-Convergence Research, Korea Institute of Radiological and Medical Sciences) ;
  • Lee, Tae Sup (RI-Convergence Research, Korea Institute of Radiological and Medical Sciences) ;
  • Kang, Joo Hyun (RI-Convergence Research, Korea Institute of Radiological and Medical Sciences) ;
  • Lee, Kyo Chul (RI-Convergence Research, Korea Institute of Radiological and Medical Sciences) ;
  • Lee, Yong Jin (RI-Convergence Research, Korea Institute of Radiological and Medical Sciences)
  • Received : 2017.11.08
  • Accepted : 2017.12.08
  • Published : 2017.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

It has been reported that $^{64}Cu$ was radiolabeled with bombesin (BBN) peptide binding to the gastrin releasing peptide receptor expressed in human prostate cancer cells (PC3), confirming tumor target efficacy in mouse model. In this study, we developed the kit for the diagnosis and treatment of prostate cancer that can be used clinically using bombesin peptide available of $^{64}Cu$ and $^{177}Lu$ radioisotope labeling. The NODAGA-galacto-BBN peptide containing the NODAGA chelator and galactose was dispensed into a sterilized glass vial and lyophilized to prepare a kit. The stability of the kit after long-term storage in the $4^{\circ}C$ cold chamber and the radiolabeling efficiency after $^{64}Cu$ or $^{177}Lu$ labeling were confirmed by thin layer chromatography. When labeling with $^{64}Cu$ at the initial stage of storage, labeling efficiency of NODAGA-galacto-BBN peptide kit was over 96%, labeling efficiency was over 90% when $^{177}Lu$ was labeled. At 11 months after storage, the radiolabeling efficiency of kit against $^{64}Cu$ and $^{177}Lu$ was each over 95% and 90%. The cell viability was significantly reduced in the $^{177}Lu$-NODAGA-galacto-BBN treated group compared with the control and $^{177}Lu$ alone treated group in clonogenic assay. In conclusion, the NODAGA-galacto-BBN kit prepared by the lyophilization showed high stability over time and high yield of radioisotope labeling. Also $^{177}Lu$-NODAGA-galacto-BBN confirmed high cytotoxicity to prostate cancer cells. Therefore, the NODAGA-galacto-bombesin kit is expected to be useful for the diagnosis and treatment of prostate cancer patients.

Keywords

References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29. https://doi.org/10.3322/caac.20138
  2. Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, Lin C, Leach C, Cannady RS, Cho H, Scoppa S, Hachey M, Kirch R, Jemal A, Ward E. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin 2012;62:220-241. https://doi.org/10.3322/caac.21149
  3. Zhang H, Desai P, Koike Y, Houghton J, Carlin S, Tandon N, Touijer K, Weber WA. Dual-Modality Imaging of Prostate Cancer with a Fluorescent and Radiogallium-Labeled Gastrin-Releasing Peptide Receptor Antagonist. J Nucl Med 2017;58:29-35. https://doi.org/10.2967/jnumed.116.176099
  4. Accardo A, Galli F, Mansi R, Del Pozzo L, Aurilio M, Morisco A, Ringhieri P, Signore A, Morelli G, Aloj L. Preclinical evaluation of eight DOTA coupled gastrin-releasing peptide receptor (GRP-R) ligands for in vivo targeting of receptor-expressing tumors. EJNMMI Res 2016;6:17 https://doi.org/10.1186/s13550-016-0175-x
  5. Dalm SU, Martens JW, Sieuwerts AM, van Deurzen CH, Koelewijn SJ, de Blois E, Maina T, Nock BA, Brunel L, Fehrentz JA, Martinez J, de Jong M, Melis M. In vitro and in vivo application of radiolabeled gastrin-releasing peptide receptor ligands in breast cancer. J Nucl Med 2015;56:752-757. https://doi.org/10.2967/jnumed.114.153023
  6. Roivainen A, Kahkonen E, Luoto P, Borkowski S, Hofmann B, Jambor I, Lehtio K, Rantala T, Rottmann A, Sipila H, Sparks R, Suilamo S, Tolvanen T, Valencia R, Minn H. Plasma pharmacokinetics, whole-body distribution, metabolism, and radiation dosimetry of 68Ga-bombesin antagonist BAY 86-7548 in healthy men. J Nucl Med 2013;54:867-872. https://doi.org/10.2967/jnumed.112.114082
  7. Kahkonen E, Jambor I, Kemppainen J, Lehtio K, Grönroos TJ, Kuisma A, Luoto P, Sipila HJ, Tolvanen T, Alanen K, Silen J, Kallajoki M, Roivainen A, Schafer N, Schibli R, Dragic M, Johayem A, Valencia R, Borkowski S, Minn H. In vivo imaging of prostate cancer using [68Ga]-labeled bombesin analog BAY86-7548. Clin Cancer Res 2013;19:5434-5443. https://doi.org/10.1158/1078-0432.CCR-12-3490
  8. Stott Reynolds TJ, Schehr R, Liu D, Xu J, Miao Y, Hoffman TJ, Rold TL, Lewis MR, Smith CJ. Characterization and evaluation of DOTA-conjugated Bombesin/RGDantagonists for prostate cancer tumor imaging and therapy. Nucl Med Biol 2015;42:99-108. https://doi.org/10.1016/j.nucmedbio.2014.10.002
  9. Kim MH, Park JA, Woo SK, Lee KC, An GI, Kim BS, Kim KI, Lee TS, Kim CW, Kim KM, Kang JH, Lee YJ. Evaluation of a 64Cu-labeled 1,4,7-triazacyclononane, 1-glutaric acid- 4,7 acetic acid (NODAGA)-galactose-bombesin analogue as a PET imaging probe in a gastrin‑releasing peptide receptor‑expressing prostate cancer xenograft model. Int J Oncol 2015;46:1159-1168. https://doi.org/10.3892/ijo.2015.2832