title: Receptor-binding, biodistribution, dosimetry, and micro-SPECT/CT imaging of 111In-[DTPA(1), Lys(3), Tyr(4)]-bombesin analog in human prostate tumor-bearing mice.
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 111InCl(3). Biologic activity of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN was evaluated in PC-3 prostate tumor-bearing severely compromised immunodeficient (SCID) mice. The purity of synthesized [DTPA(1), Lys(3), Tyr(4)]-BN was greater than 95%. The radiolabeling efficiency of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN was 96.9% +/- 2.46%. The IC(50) and K(i) of [DTPA(1), Lys(3), Tyr(4)]-BN in the human bombesin 2 receptor were 1.05 +/- 0.46 and 0.83 +/- 0.36 nM, respectively. The K(d) of 111In-[DTPA(1), Lys(3), Tyr(4)]-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-[DTPA(1), Lys(3), Tyr(4)]-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), Lys(3), Tyr(4)]-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), Lys(3), Tyr(4)]-BN is a potential agent for imaging GRPR-positive tumors in humans.
authors.affiliation: Institute of Nuclear Energy Research, Taoyuan, Taiwan, Republic of China.
authors.forename: Chung-Li
authors.initials: CL
authors.lastname: Ho
authors.forename: Liang-Cheng
authors.initials: LC
authors.lastname: Chen
authors.forename: Wan-Chi
authors.initials: WC
authors.lastname: Lee
authors.forename: Shu-Pei
authors.initials: SP
authors.lastname: Chiu
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Hsu
authors.forename: Yu-Hsien
authors.initials: YH
authors.lastname: Wu
authors.forename: Chung-Hsin
authors.initials: CH
authors.lastname: Yeh
authors.forename: Michael G
authors.initials: MG
authors.lastname: Stabin
authors.forename: Meei-Ling
authors.initials: ML
authors.lastname: Jan
authors.forename: Wuu-Jyh
authors.initials: WJ
authors.lastname: Lin
authors.forename: Te-Wei
authors.initials: TW
authors.lastname: Lee
authors.forename: Chih-Hsien
authors.initials: CH
authors.lastname: Chang
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001839:Bombesin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004355:Drug Stability; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes / Q000737:chemistry; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D051379:Mice; D016513:Mice, SCID; D004369:Pentetic Acid / Q000493:pharmacokinetics*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics*; D011879:Radiotherapy Dosage; D018004:Receptors, Bombesin / Q000737:chemistry / Q000378:metabolism*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014057:Tomography, X-Ray Computed
chemical_list: C545609:DTPA(1)-Lys(3),Tyr(4)bombesin; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D018004:Receptors, Bombesin; D004369:Pentetic Acid; D001839:Bombesin