19694578

pubmed:Citation

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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.

http://linkedlifedata.com/resource/pubmed/journal/9605408

http://linkedlifedata.com/resource/pubmed/chemical/Bombesin, http://linkedlifedata.com/resource/pubmed/chemical/Indium Radioisotopes, http://linkedlifedata.com/resource/pubmed/chemical/Pentetic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Radiopharmaceuticals, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Bombesin

Aug

pubmed-author:ChangChih-HsienCH, pubmed-author:ChenLiang-ChengLC, pubmed-author:ChiuShu-PeiSP, pubmed-author:HoChung-LiCL, pubmed-author:HsuWei-ChuanWC, pubmed-author:JanMeei-LingML, pubmed-author:LeeTe-WeiTW, pubmed-author:LeeWan-ChiWC, pubmed-author:LinWuu-JyhWJ, pubmed-author:StabinMichael GMG, pubmed-author:WuYu-HsienYH, pubmed-author:YehChung-HsinCH

24

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pubmed-meshheading:19694578-Animals, pubmed-meshheading:19694578-Binding, Competitive, pubmed-meshheading:19694578-Bombesin, pubmed-meshheading:19694578-Cell Line, Tumor, pubmed-meshheading:19694578-Disease Models, Animal, pubmed-meshheading:19694578-Drug Stability, pubmed-meshheading:19694578-Female, pubmed-meshheading:19694578-Humans, pubmed-meshheading:19694578-Indium Radioisotopes, pubmed-meshheading:19694578-Isotope Labeling, pubmed-meshheading:19694578-Male, pubmed-meshheading:19694578-Mice, pubmed-meshheading:19694578-Mice, SCID, pubmed-meshheading:19694578-Pentetic Acid, pubmed-meshheading:19694578-Prostatic Neoplasms, pubmed-meshheading:19694578-Radiometry, pubmed-meshheading:19694578-Radiopharmaceuticals, pubmed-meshheading:19694578-Radiotherapy Dosage, pubmed-meshheading:19694578-Receptors, Bombesin, pubmed-meshheading:19694578-Tissue Distribution, pubmed-meshheading:19694578-Tomography, Emission-Computed, Single-Photon, pubmed-meshheading:19694578-Tomography, X-Ray Computed

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.

Journal Article