대한방사성의약품학회지 (Journal of Radiopharmaceuticals and Molecular Probes)

  • 제4권2호
  • /
  • Pages.65-72
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  • 2018
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  • 2384-1583(pISSN)
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  • 2508-3848(eISSN)
대한방사성의약품학회 (Korean Society of Radiopharmaceuticals and Molecular Probes)
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Synthesis and biological evaluation of diagnostic reagent for prostate cancer using copper-64 radioisotope

  • Ahn, Heesu (Division of Applied RI, Korea Institute of Radiological and Medical Sciences) ;
  • Kim, Mi Hyun (FutureChem Healthcare Co., Ltd.) ;
  • Han, Sang Jin (Division of Applied RI, Korea Institute of Radiological and Medical Sciences) ;
  • Woo, Sang Keun (Division of Applied RI, Korea Institute of Radiological and Medical Sciences) ;
  • Kim, Jung Young (Division of Applied RI, Korea Institute of Radiological and Medical Sciences) ;
  • Lee, Kyu Chul (Division of Applied RI, Korea Institute of Radiological and Medical Sciences) ;
  • Lim, Il Han (Division of Applied RI, Korea Institute of Radiological and Medical Sciences) ;
  • Lee, Yong Jin (Division of Applied RI, Korea Institute of Radiological and Medical Sciences)
  • 투고 : 2018.12.11
  • 심사 : 2018.12.23
  • 발행 : 2018.12.30
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초록

Prostate specific membrane antigen (PSMA) is a cell surface membrane protein, which is overexpressed in most prostate cancer. Recently, PET imaging with $[^{68}Ga]$PSMA-HBED-CC has been widely used for the diagnosis of recurrent prostate cancer and the studies on the diagnostic potential of $^{64}Cu$-labeled PSMA ligands reported actively. In this study, we monitored with biological evaluation in vivo and PET imaging of $^{64}Cu$-labeled PSMA ligand ($[^{64}Cu]$PSMA-617). The radiolabelling efficiency and stability of $[^{64}Cu]$PSMA-617 were confirmed by radio-thin layer chromatography. The radiolabeling efficiency of $[^{64}Cu]$PSMA-617 showed over 95%, and stabilities of intact remained over 98% in both human and mouse serum for 48 h. In normal male mice, in vivo uptake of $[^{64}Cu]$PSMA-617 in several organs was measured at 2, 4, 6, 24, 48 h after injection. Rapid blood clearance was observed for $[^{64}Cu]$PSMA-617. The high uptake was observed in the lung, liver, intestines and kidneys at 2 h postinjection, but was low in the other organs (1-2 %ID/g) at 4 h. The dynamic PET/CT images of 22RV1 tumor-bearing nude mice were acquired during 60 min and additionally acquired 24 h and 48 h after injection. In dynamic PET images, $[^{64}Cu]$PSMA-617 uptake ratio in tumors versus muscle was increased as time elaplsed until 60 minutes and remained in tumors at 48 h. In these results, the PET/CT imaging using $[^{64}Cu]$PSMA-617 in prostate cancer is expected to be useful for the diagnosis and treatment of prostate cancer patients.

키워드

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Scheme 1. Synthetic route of precursor for [64Cu]PSMA-617.

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Figure 1. Chromatogram of [64Cu]PSMA-617. (A) It is a radio-TLC peak image of free Cu-64: Rf=1.0 (B) It is a radio-TLC peak image of [64Cu]PSMA-617: Rf=0.5

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Figure 2. In vitro serum stability assay. (A) It is radio-TLC peak images of [64Cu] PSMA-617 after incubation in human serum, mouse serum and saline during 0, 4, 24, 48 h. (B) It is a graph of stability (%) of [64Cu]PSMA-617 after incubation in human serum, mouse serum and saline during 0, 4, 24, 48h.

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Figure 3. PSMA mRNA or protein expression level of human prostate cancer cell line 22RV1, LNCaP, PC3 and PC3-M. (A) It is a RT-PCR band for PSMA mRNA expression. (B) It is a western blot band for PSMA protein expression. The GAPDH expression is used for control.

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Figure 4. In vitro cell uptake assay. It is a time-dependent graph of [64Cu]PSMA-617 in human prostate cancer cell line PC3, 22RV1 and LNCap.

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Figure 5. The biodistribution (%ID/g) of radioactivity in Balb/c (nu/nu) mice (n=4) after the injection of [64Cu]PSMA-617 at 2, 4, 6, 24, 48h. The tissue uptake at 2 h is highest and decreased via liver and kidney during 48 h.

DHBSB1_2018_v4n2_65_f0007.png 이미지

Figure 6. The PET/CT imaging of 22RV1 prostate xenograft tumor model after injection [64Cu]PSMA-617. (A) It is a dynamic PET/CT image after 30-60 min of [64Cu]PSMA-617 injection in 22RV1 prostate xenograft tumor model. (B) It is a time-dependent graph of tumor to muscle uptake ratio. (C) It is a static PET/CT image of [64Cu]PSMA-617 injection in 22RV1 prostate xenograft tumor model at 24 h, 48 h.

Table 1. The biodistribution (%ID/g) of radioactivity in Balb/c (nu/nu) mice (n=4) after the injection of [64Cu]PSMA-617 at 2, 4, 6, 24, 48h.

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