Development of a 68Ga-peptide tracer for PET GnRH1-imaging

Zoghi, Masoumeh; Jalilian, Amir Reza; Ниази, Али; Johari-Daha, Fariba; Alirezapour, Behrouz; Saeed, Ramezanpour

doi:10.1007/s12149-016-1074-y

Cited by 10 publications

(10 citation statements)

References 25 publications

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“…GnRH peptide analogues labeled with positron-emitting radionuclides are of particular interest due to the high spatial resolution and sensitivity of PET [19]. Recently, Zoghi et al developed [ 68 Ga]-labeled DOTA-triptorelin as a possible PET radiotracer for GnRH receptor imaging [17]. The biodistribution of the tracer was determined in normal male rats and 4T1 tumor-bearing mice.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of ¹⁸F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging

Huang

Han

et al. 2019

Contrast Media & Molecular Imaging

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The gonadotropin-releasing hormone (GnRH) receptor is overexpressed in the majority of tumors of the human reproductive system. The purpose of this study was to develop an 18F-labeled peptide for tumor GnRH receptor imaging. In this study, the GnRH (pGlu1-His2-Trp3-Ser4-Tyr5-Gly6-Leu7-Arg8-Pro9-Gly10-NH2) peptide analogues FP-D-Lys6-GnRH (FP = 2-fluoropropanoyl) and NOTA-P-D-Lys6-GnRH (P = ethylene glycol) were designed and synthesized. The IC50 values of FP-D-Lys6-GnRH and NOTA-P-D-Lys6-GnRH were 2.0 nM and 56.2 nM, respectively. 4-Nitrophenyl-2-[18F]fluoropropionate was conjugated to the ε-amino group of the D-lysine side chain of D-Lys6-GnRH to yield the new tracer [18F]FP-D-Lys6-GnRH with a decay-corrected yield of 8 ± 3% and a specific activity of 20−100 GBq/µmol (n=6). Cell uptake studies of [18F]FP-D-Lys6-GnRH in GnRH receptor-positive PC-3 cells and GnRH receptor-negative CHO-K1 cells indicated receptor-specific accumulation. Biodistribution and PET studies in nude mice bearing PC-3 xenografted tumors showed that [18F]FP-D-Lys6-GnRH was localized in tumors with a higher uptake than in surrounding muscle and heart tissues. Furthermore, the metabolic stability of [18F]FP-D-Lys6-GnRH was determined in mouse blood and PC-3 tumor homogenates at 1 h after tracer injection. The presented results indicated a potential of the novel tracer [18F]FP-D-Lys6-GnRH for tumor GnRH receptor imaging.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of ¹⁸F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging

Huang

Han

et al. 2019

Contrast Media & Molecular Imaging

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“…In vivo studies were done by three different procedures. The triptorelin‐hydrazide labeled with 177 Lu was evaluated in vitro using GnRH‐I expressing on the human prostatic carcinoma cell line LNCaP to determine receptor affinity and to assess internalization efficiency . Moreover, serum stability study was performed for 177 Lu‐DOTA‐TRPHYD.…”

Section: Introductionmentioning

confidence: 99%

Preclinical evaluation of new GnRH‐I receptor radionuclide therapy with ¹⁷⁷Lu‐peptide tracer

Zoghi

Nosrati

Rogni

et al. 2019

Labelled Comp Radiopharmac

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The purpose of this study was to develop preclinical evaluation of a novel radiolabeled gonadotropin-releasing hormone (GnRH) receptor targeting peptide for prostate cancer therapy. The new antiproliferative agent of GnRH-I analogue was developed on the basis of the D-Trp 6 -GnRH-I scaffold, and in vivo pharmacokinetics and receptor binding affinity were enhanced by the substitution of Gly-NHNH 2 for Gly-NH 2 at position 10 in D-Trp 6 -GnRH-I. To evaluate 177 Lu-DOTA-triptorelin-hydrazide as radionuclide therapy of tumor, the quality control tests and preclinical stage assessment were carried out.Solid-phase method was used to synthesize new peptide. Characterization and purity of peptide were done by mass spectroscopy and high-performance liquid chromatography (HPLC). In order to be utilized in targeted therapy, the new GnRH-I agonist was coupled with pSCN-Bn-DOTA. The precipitate crude of DOTA-triptorelin-hydrazide was then purified via preparative HPLC. At optimal conditions of time, temperature, ligand amount, and lutetium content, DOTA-triptorelin-hydrazide was labeled with 177 Lu (specific activity not less than 925 GBq/mg). Investigation of the in vivo biodistribution and in vitro studies for 177 Lu-DOTA-TRPHYD was performed in three different ways, and the binding of radiopeptide to GnRH receptors was expressed on the human cell lines using 125 I-labeled D-TRP 6 GnRH-I as a tracer, respectively.Synthesized novel GnRH-I was obtained with purity greater than 98%. Paper chromatography was found to be the most suitable with R f of the complex and observed radiochemical purity of RTLC and HPLC greater than 97%. For in vivo studies, 177 Lu-DOTA-triptorelin-hydrazide showed promising results with fast clearance from the blood and resulted in good T/NT ratios at 1, 4, and 24 hours postinjection and satisfactory biodistribution with no significant activity seen in normal tissue. The values of internalization efficiency and receptor affinity of new radiopeptide binding were IC 50 = 0.47 ± 0.06 vs 0.13 ± 0.01 nM for triptorelin and cellular uptake: 3.4 ± 0.7% at 1 hour and 6.8 ± 1.17% at 4 hours of the internal reference. The results showed a good stability and radiochemical purity of the obtained radioconjugate. For in vivo and in vitro studies, new radiopeptide showed a high uptake of 177 Lu conjugate in tumor and rapid clearance from the blood stream almost entirely via the

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“…)(22–24). Zoghi et al from Iran reported on the synthesis and biodistribution studies of 68 Ga-DOTA-triptorelin ( 68 Ga-DOTA-TRP) as a PET radioligand targeted to the GnRH-R (25). The authors reported a robust synthesis scheme with the radiotracer biodistribution demonstrating significant uptake in kidney (excretion route), stomach, and testes.…”

Section: Oncologymentioning

confidence: 99%

Highlights of articles published in annals of nuclear medicine 2016

Jadvar

2017

Eur J Nucl Med Mol Imaging

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This article is the first installment of highlights of selected articles published during 2016 in the Annals of Nuclear Medicine, an official peer-reviewed journal of the Japanese Society of Nuclear Medicine. A companion article highlighting selected articles published during 2016 in the European Journal of Nuclear Medicine and Molecular Imaging, which is the official peer-reviewed journal of the European Association of Nuclear Medicine, will also appear in the Annals Nuclear Medicine. This new initiative by the respective journals will continue as an annual endeavor and is anticipated to not only enhance the scientific collaboration between Europe and Japan but also facilitate global partnership in the field of nuclear medicine and molecular imaging.

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Development of a 68Ga-peptide tracer for PET GnRH1-imaging

Cited by 10 publications

References 25 publications

Synthesis and Evaluation of ¹⁸F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging

Synthesis and Evaluation of ¹⁸F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging

Preclinical evaluation of new GnRH‐I receptor radionuclide therapy with ¹⁷⁷Lu‐peptide tracer

Highlights of articles published in annals of nuclear medicine 2016

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Development of a 68Ga-peptide tracer for PET GnRH1-imaging

Cited by 10 publications

References 25 publications

Synthesis and Evaluation of 18F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging

Synthesis and Evaluation of 18F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging

Preclinical evaluation of new GnRH‐I receptor radionuclide therapy with 177Lu‐peptide tracer

Highlights of articles published in annals of nuclear medicine 2016

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Synthesis and Evaluation of ¹⁸F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging

Synthesis and Evaluation of ¹⁸F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging

Preclinical evaluation of new GnRH‐I receptor radionuclide therapy with ¹⁷⁷Lu‐peptide tracer