nach oben

Molecular Imaging and Biology

Erschienen in:

18.06.2018 | Research Article

Noninvasive PET Imaging of a Ga-68-Radiolabeled RRL-Derived Peptide in Hepatocarcinoma Murine Models

verfasst von: Yan Huo, Lei Kang, Xiaoxi Pang, Haoyuan Shen, Ping Yan, Chunli Zhang, Xuhe Liao, Xueqi Chen, Rongfu Wang

Erschienen in: Molecular Imaging and Biology | Ausgabe 2/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Tc-99m- and I-131-labeled arginine-arginine-leucine (RRL) peptides have shown the feasibility of tumor imaging in our previous studies. However, there have been no reports using RRL peptide for positron emission tomography (PET) imaging. In this study, RRL was radiolabeled with Ga-68 under optimized reaction conditions to develop a better specific and effective tumor imaging agent.

Procedures

RRL was synthesized and conjugated to a bifunctional chelating agent (DOTA-NHS), then radiolabeled with Ga-68. Labeling yield was optimized by varying pH, temperature, and reaction time and the stability was evaluated in human fresh serum. Cellular uptakes of [⁶⁸Ga]DOTA-RRL and FITC-conjugated RRL in HepG2 cells were evaluated using a gamma counter, confocal microscopy, and flow cytometry. PET images and biodistribution were performed in HepG2 tumor-bearing mice after injection of [⁶⁸Ga]DOTA-RRL or [⁶⁸Ga]GaCl₃ at different time points. Further, blocking study was investigated using cold RRL.

Results

The labeling yield of [⁶⁸Ga]DOTA-RRL was 80.6 ± 3.9 % with a pH of 3.5–4.5 at 100 °C for 15 min. The cellular uptake of [⁶⁸Ga]DOTA-RRL in HepG2 cells was significantly higher than that of [⁶⁸Ga]GaCl₃ (P < 0.05). Moreover, the high fluorescent affinity of FITC-conjugated RRL in HepG2 cells was shown using confocal microscopy and flow cytometry. After injection of [⁶⁸Ga]DOTA-RRL in HepG2 tumor-bearing mice, tumor regions exhibited high radioactive accumulation over 120 min and the highest uptake at 30 min. After blocked with cold RRL, HepG2 tumors could not be visualized. [⁶⁸Ga]GaCl₃ was unable to show tumor images at any time point. The biodistribution results confirmed the PET imaging and blocking results.

Conclusions

Our study successfully prepared [⁶⁸Ga]DOTA-RRL with a high labeling yield under the optimized reaction conditions and demonstrated its potential role as a PET imaging agent for tumor-targeted diagnosis.

Nur mit Berechtigung zugänglich

Sun X, Li Y, Liu T et al (2016) Peptide-based imaging agents for cancer detection. Adv Drug Deliv Rev 110-111:38–51CrossRefPubMedPubMedCentral

Brown CK, Modzelewski RA, Johnson CS, Wong MK (2000) A novel approach for the identification of unique tumor vasculature binding peptides using an E. coli peptide display library. Ann Surg Oncol 7:743–749CrossRefPubMed

Lu X, Wang RF (2012) A concise review of current radiopharmaceuticals in tumor angiogenesis imaging. Curr Pharm Des 18:1032–1040CrossRefPubMed

Weller GE, Wong MK, Modzelewski RA, Lu E, Klibanov AL, Wagner WR, Villanueva FS (2005) Ultrasonic imaging of tumor angiogenesis using contrast microbubbles targeted via the tumor-binding peptide arginine-arginine-leucine. Cancer Res 65:533–539PubMed

Weller GE, Villanueva FS, Klibanov AL, Wagner WR (2002) Modulating targeted adhesion of an ultrasound contrast agent to dysfunctional endothelium. Ann Biomed Eng 30:1012–1019CrossRefPubMed

Lu X, Yan P, Wang RF, Liu M, Yu MM, Zhang CL (2012) Use of radioiodinated peptide Arg-Arg-Leu targeted to neovascularization as well as tumor cells in molecular tumor imaging. Chinese J Cancer Res 24:52–59CrossRef

Kim DW, Kim WH, Kim MH, Kim CG (2015) Synthesis and evaluation of Tc-99m-labeled RRL-containing peptide as a non-invasive tumor imaging agent in a mouse fibrosarcoma model. Ann Nucl Med 29:779–785CrossRefPubMed

Yu M, Zhou H, Liu X et al (2010) Study on biodistribution and imaging of radioiodinated arginine-arginine-leucine peptide in nude mice bearing human prostate carcinoma. Ann Nucl Med 24:13–19CrossRefPubMed

Zhao Q, Yan P, Yin L et al (2013) Validation study of (1)(3)(1)I-RRL: assessment of biodistribution, SPECT imaging and radiation dosimetry in mice. Mol Med Rep 7:1355–1360CrossRefPubMed

10.

Zhao Q, Yan P, Wang RF et al (2013) A novel ^99mTc-labeled molecular probe for tumor angiogenesis imaging in hepatoma xenografts model: a pilot study. PLoS One 8:e61043CrossRefPubMedPubMedCentral

11.

Lu X, Zhao L, Xue T, Zhang H (2013) Technetium-99m-Arg-Arg-Leu(g2), a modified peptide probe targeted to neovascularization in molecular tumor imaging. J BUON 18:1074–1081PubMed

12.

Yao N, Yan P, Wang RF, Zhang CL, Ma C, Chen XQ, Zhao Q, Hao P (2015) Detection of pulmonary metastases with the novel radiolabeled molecular probe, ^99mTc-RRL. Int J Clin Exp Med 8:1726–1736PubMedPubMedCentral

13.

Kang L, Wang RF, Yan P, Liu M, Zhang CL, Yu MM, Cui YG, Xu XJ (2010) Noninvasive visualization of RNA delivery with 99mTc-radiolabeled small-interference RNA in tumor xenografts. J Nucl Med 51:978–986CrossRefPubMed

14.

Lang L, Li W, Guo N, Ma Y, Zhu L, Kiesewetter DO, Shen B, Niu G, Chen X (2011) Comparison study of [¹⁸F]FAl-NOTA-PRGD2, [18F]FPPRGD2, and [⁶⁸Ga]Ga-NOTA-PRGD2 for PET imaging of U87MG tumors in mice. Bioconjug Chem 22:2415–2422CrossRefPubMedPubMedCentral

15.

Oxboel J, Brandt-Larsen M, Schjoeth-Eskesen C, Myschetzky R, el-Ali HH, Madsen J, Kjaer A (2014) Comparison of two new angiogenesis PET tracers ⁶⁸Ga-NODAGA-E[c(RGDyK)]2 and ⁶⁴Cu-NODAGA-E[c(RGDyK)]2; in vivo imaging studies in human xenograft tumors. Nucl Med Biol 41:259–267CrossRefPubMed

16.

Notni J, Pohle K, Wester HJ (2012) Comparative gallium-68 labeling of TRAP-, NOTA-, and DOTA-peptides: practical consequences for the future of gallium-68-PET. EJNMMI Res 2:28CrossRefPubMedPubMedCentral

17.

Shan L (2004) ¹³¹I-Labeled arginine-arginine-leucine (RRL)-containing cyclic peptide (YCGGRRLGGC) for imaging prostate carcinoma. In: Molecular Imaging and Contrast Agent Database (MICAD). Bethesda (MD)

18.

Geng H, Jiang F, Wu YD (2016) Accurate structure prediction and conformational analysis of cyclic peptides with residue-specific force fields. J Phys Chem Lett 7:1805–1810CrossRefPubMed

19.

Price EW, Orvig C (2014) Matching chelators to radiometals for radiopharmaceuticals. Chem Soc Rev 43:260–290CrossRefPubMed

20.

Poschenrieder A, Schottelius M, Schwaiger M, Wester HJ (2016) Preclinical evaluation of [⁶⁸Ga]NOTA-pentixafor for PET imaging of CXCR4 expression in vivo—a comparison to [⁶⁸Ga]pentixafor. EJNMMI Res 6:70CrossRefPubMedPubMedCentral

21.

Zhao N, Qin Y, Liu H, Cheng Z (2018) Tumor-targeting peptides: ligands for molecular imaging and therapy. Anti Cancer Agents Med Chem 18:74–86CrossRef

22.

Romero E, Martinez A, Oteo M et al (2016) Preparation of ⁶⁸Ga-labelled DOTA-peptides using a manual labelling approach for small-animal PET imaging. Appl Radiat Isot 107:113–120CrossRefPubMed

23.

Tolmachev V, Velikyan I, Sandstrom M, Orlova A (2010) A HER2-binding Affibody molecule labelled with ⁶⁸Ga for PET imaging: direct in vivo comparison with the 111In-labelled analogue. Eur J Nucl Med Mol Imaging 37:1356–1367CrossRefPubMed

24.

Mohsin H, Fitzsimmons J, Shelton T, Hoffman TJ, Cutler CS, Lewis MR, Athey PS, Gulyas G, Kiefer GE, Frank RK, Simon J, Lever SZ, Jurisson SS (2007) Preparation and biological evaluation of ¹¹¹In-, ¹⁷⁷Lu- and ⁹⁰Y-labeled DOTA analogues conjugated to B72.3. Nucl Med Biol 34:493–502CrossRefPubMed

25.

Antunes P, Ginj M, Zhang H, Waser B, Baum RP, Reubi JC, Maecke H (2007) Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals? Eur J Nucl Med Mol Imaging 34:982–993CrossRefPubMed

26.

Jackson GE, Byrne MJ (1996) Metal ion speciation in blood plasma: gallium-67-citrate and MRI contrast agents. J Nucl Med 37:379–386PubMed

27.

Fortin MA, Orlova A, Malmstrom PU, Tolmachev V (2007) Labelling chemistry and characterization of [⁹⁰Y/¹⁷⁷Lu]-DOTA-ZHER2:342-3 Affibody molecule, a candidate agent for locoregional treatment of urinary bladder carcinoma. Int J Mol Med 19:285–291PubMed

Titel: Noninvasive PET Imaging of a Ga-68-Radiolabeled RRL-Derived Peptide in Hepatocarcinoma Murine Models
verfasst von: Yan Huo
Lei Kang
Xiaoxi Pang
Haoyuan Shen
Ping Yan
Chunli Zhang
Xuhe Liao
Xueqi Chen
Rongfu Wang
Publikationsdatum: 18.06.2018
Verlag: Springer International Publishing
Erschienen in: Molecular Imaging and Biology / Ausgabe 2/2019
Print ISSN: 1536-1632
Elektronische ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-018-1234-7

Neu im Fachgebiet Radiologie

18.04.2024 | Pädiatrische Notfallmedizin | Nachrichten

Update Radiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Noninvasive PET Imaging of a Ga-68-Radiolabeled RRL-Derived Peptide in Hepatocarcinoma Murine Models

Abstract

Purpose

Procedures

Results

Conclusions

Neu im Fachgebiet Radiologie

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

Wie toxische Männlichkeit der Gesundheit von Männern schadet

Studie bestätigt Potenzial von KI in der Radiologie

Quantitative Angiografie könnte IVUS-Alternative darstellen

Update Radiologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose

Procedures

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2019

Linked Hexokinase and Glucose-6-Phosphatase Activities Reflect Grade of Ovarian Malignancy

Differentiation of Malignant and Benign Head and Neck Tumors with Amide Proton Transfer-Weighted MR Imaging

Imaging Cobalamin Uptake within Malignant Breast Tumors In Vivo

How Long of a Dynamic 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) PET Acquisition Is Needed for Robust Kinetic Analysis in Breast Cancer?

In Vivo Evaluation of Magnetic Targeting in Mice Colon Tumors with Ultra-Magnetic Liposomes Monitored by MRI

Near-Infrared Spatially Resolved Spectroscopy as an Indirect Technique to Assess Brown Adipose Tissue in Young Women

Neu im Fachgebiet Radiologie

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

Wie toxische Männlichkeit der Gesundheit von Männern schadet

Studie bestätigt Potenzial von KI in der Radiologie

Quantitative Angiografie könnte IVUS-Alternative darstellen

Update Radiologie