Receptor-binding, biodistribution, dosimetry, and micro-SPECT/CT imaging of 111In-[DTPA1, Lys3, Tyr4]-bombesin analog in human prostate tumor-bearing mice

Chung Li Ho, Liang Cheng Chen, Wan Chi Lee, Shu Pei Chiu, Wei Chuan Hsu, Yu Hsien Wu, Chung Hsin Yeh, Michael G. Stabin, Meei Ling Jan, Wuu Jyh Lin, Te Wei Lee, Chih Hsien Chang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

16 Scopus citations

Abstract

Gastrin-releasing peptide receptors (GRPRs) are overexpressed on a variety of human tumors, such as prostate, breast, and lung cancer. Bombesin (BN) is a 14-amino-acid peptide with high affinity for these GRPRs. We synthesized DTPA-Q-K-Y-G-N-Q-W-A-V-G-H-L-M, a 13-amino-acid peptide chelated with diethylenetriaminepentaacetic acid (DTPA), and radiolabeled this BN analog with 111InCl3. Biologic activity of 111In-[DTPA 1, Lys3, Tyr4]-BN was evaluated in PC-3 prostate tumor-bearing severely compromised immunodeficient (SCID) mice. The purity of synthesized [DTPA1, Lys3, Tyr4]-BN was greater than 95%. The radiolabeling efficiency of 111In- [DTPA1, Lys3, Tyr4]-BN was 96.9% ± 2.46%. The IC50 and Ki of [DTPA1, Lys 3, Tyr4]-BN in the human bombesin 2 receptor were 1.05 ± 0.46 and 0.83 ± 0.36 nM, respectively. The Kd of 111In-[DTPA1, Lys3, Tyr4]-BN in GRPR-expressing PC-3 tumor cells was 22.9 ± 6.81 nM. Both biodistribution and micro-SPECT/CT (single-photon emission computed tomography/computed tomography) imaging studies with 111In-[DTPA1, Lys 3, Tyr4]-BN demonstrated the highest uptake at 8 hours postinjection. The Pearson correlation analysis showed a positive correlation of tumor uptake between biodistribution and micro-SPECT/CT semiquantification imaging analysis (r = 0.832). Our results revealed 111In-[DTPA 1, Lys3, Tyr4]-BN has high affinity with BN type 2 receptor. The results demonstrated a good uptake in the GRPR-overexpression of PC-3 tumor-bearing SCID mice. 111In-[DTPA 1, Lys3, Tyr4]-BN is a potential agent for imaging GRPR-positive tumors in humans.

Original languageEnglish
Pages (from-to)435-443
Number of pages9
JournalCancer Biotherapy and Radiopharmaceuticals
Volume24
Issue number4
DOIs
StatePublished - 01 08 2009
Externally publishedYes

Keywords

  • Bombesin analogs
  • Gastrin-releasing peptide receptor
  • Molecular imaging
  • Prostate cancer

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