scholarly journals Gallium Ga 68-labeled GRPR Antagonist BAY86-7548

2020 ◽  
Author(s):  
Keyword(s):  
Grpr Antagonist

scholarly journals [99mTc]Tc-DB15 in GRPR-Targeted Tumor Imaging with SPECT: From Preclinical Evaluation to the First Clinical Outcomes

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5093
Author(s):  
Berthold A. Nock ◽  
Aikaterini Kaloudi ◽  
Panagiotis Kanellopoulos ◽  
Barbara Janota ◽  
Barbara Bromińska ◽  
...  
Keyword(s):  
Tumor Imaging ◽  
Pharmacokinetic Profile ◽  
Diglycolic Acid ◽  
Preclinical Evaluation ◽  
Peptide Receptor ◽  
Gastrin Releasing Peptide ◽  
Specific Uptake ◽  
Grpr Antagonist

Diagnostic imaging and radionuclide therapy of prostate (PC) and breast cancer (BC) using radiolabeled gastrin-releasing peptide receptor (GRPR)-antagonists represents a promising approach. We herein propose the GRPR-antagonist based radiotracer [99mTc]Tc-DB15 ([99mTc]Tc-N4-AMA-DGA-DPhe6,Sar11,LeuNHEt13]BBN(6-13); N4: 6-carboxy-1,4,8,11-tetraazaundecane, AMA: aminomethyl-aniline, DGA: diglycolic acid) as a new diagnostic tool for GRPR-positive tumors applying SPECT/CT. The uptake of [99mTc]Tc-DB15 was tested in vitro in mammary (T-47D) and prostate cancer (PC-3) cells and in vivo in T-47D or PC-3 xenograft-bearing mice as well as in BC patients. DB15 showed high GRPR-affinity (IC50 = 0.37 ± 0.03 nM) and [99mTc]Tc-DB15 strongly bound to the cell-membrane of T-47D and PC-3 cells, according to a radiolabeled antagonist profile. In mice, the radiotracer showed high and prolonged GRPR-specific uptake in PC-3 (e.g., 25.56 ± 2.78 %IA/g vs. 0.72 ± 0.12 %IA/g in block; 4 h pi) and T-47D (e.g., 15.82 ± 3.20 %IA/g vs. 3.82 ± 0.30 %IA/g in block; 4 h pi) tumors, while rapidly clearing from background. In patients with advanced BC, the tracer could reveal several bone and soft tissue metastases on SPECT/CT. The attractive pharmacokinetic profile of [99mTc]DB15 in mice and its capability to target GRPR-positive BC lesions in patients highlight its prospects for a broader clinical use, an option currently being explored by ongoing clinical studies.

scholarly journals 68 Ga/ 177 Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology

2016 ◽  
Vol 58 (2) ◽  
pp. 293-299 ◽  
Author(s):  
Simone U. Dalm ◽  
Ingrid L. Bakker ◽  
Erik de Blois ◽  
Gabriela N. Doeswijk ◽  
Mark W. Konijnenberg ◽  
...  
Keyword(s):  
Grpr Antagonist

scholarly journals Trastuzumab cotreatment improves survival of mice with PC‐3 prostate cancer xenografts treated with the GRPR antagonist 177 Lu‐DOTAGA‐PEG 2 ‐RM26

2019 ◽  
Vol 145 (12) ◽  
pp. 3347-3358 ◽  
Author(s):  
Bogdan Mitran ◽  
Sara S. Rinne ◽  
Mark W. Konijnenberg ◽  
Theodosia Maina ◽  
Berthold A. Nock ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Grpr Antagonist

scholarly journals Synthesis and evaluation of [186Re]Re(CO)3-p-NCS-benzyl-NODAGA-Ser2-RM2 for future development as a GRPR-antagonist for targeting prostate cancer

2021 ◽  
Vol 96-97 ◽  
pp. S90-S91
Author(s):  
Rebecca Hoerres ◽  
Pavithra H.A. Kankanamalage ◽  
Fabio Gallazzi ◽  
Heather Hennkens
Keyword(s):  
Prostate Cancer ◽  
Future Development ◽  
Grpr Antagonist

scholarly journals GRPr antagonist 68Ga-SB3 PET/CT-imaging of primary prostate cancer in therapy-naive patients

2021 ◽  
pp. jnumed.120.258814
Author(s):  
Ingrid L Bakker ◽  
Alida C Fröberg ◽  
Martijn B Busstra ◽  
J. Fred Verzijlbergen ◽  
Mark Konijnenberg ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Ct Imaging ◽  
Primary Prostate Cancer ◽  
Pet Ct ◽  
Grpr Antagonist

scholarly journals Bombesin receptor-targeted liposomes for enhanced delivery to lung cancer cells

2019 ◽  
Vol 10 ◽  
pp. 2553-2562
Author(s):  
Mohammad J Akbar ◽  
Pâmela C Lukasewicz Ferreira ◽  
Melania Giorgetti ◽  
Leanne Stokes ◽  
Christopher J Morris
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Storage Conditions ◽  
Lung Cancer Cells ◽  
Gastrin Releasing Peptide ◽  
Antagonist Peptides ◽  
Microscopic Studies ◽  
Grpr Antagonist

Background: Gastrin-releasing peptide is a member of the bombesin family of peptides. Its cognate receptor, gastrin releasing peptide receptor (GRPR), is widely expressed in cancers of the lung, pancreas and ovaries. Gastrin releasing peptide (GRP) is an autocrine growth factor in small cell lung cancer, which has very poor patient outcomes. High affinity antagonist peptides have been developed for in vivo cancer imaging. In this report we decorated pegylated liposomes with a GRPR antagonist peptide and studied its interaction with, and accumulation within, lung cancer cells. Results: An N-terminally cysteine modified GRPR antagonist (termed cystabn) was synthesised and shown to inhibit cell growth in vitro. Cystabn was used to prepare a targeted 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000) lipid conjugate that was formulated into liposomes. The liposomes displayed desirable colloidal properties and good stability under storage conditions. Flow cytometric and microscopic studies showed that fluorescently labelled cystabn-decorated liposomes accumulated more extensively in GRPR over-expressing cells than matched liposomes that contained no cystabn targeting motif. Conclusion: The use of GRPR antagonistic peptides for nanoparticle targeting has potential for enhancing drug accumulation in resistant cancer cells.

scholarly journals Preclinical Evaluation of the Copper-64 Labeled GRPR-Antagonist RM26 in Comparison with the Cobalt-55 Labeled Counterpart for PET-Imaging of Prostate Cancer

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5993
Author(s):  
Christina Baun ◽  
Bogdan Mitran ◽  
Sara S. Rinne ◽  
Johan H. Dam ◽  
Birgitte B. Olsen ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Late Time ◽  
Vitro Binding ◽  
Pet Ct ◽  
Liver And Pancreas ◽  
Prostate Cancers ◽  
Grpr Antagonist ◽  
Late Time Point

Gastrin-releasing peptide receptor (GRPR) is overexpressed in the majority of prostate cancers. This study aimed to investigate the potential of 64Cu (radionuclide for late time-point PET-imaging) for imaging of GRPR expression using NOTA-PEG2-RM26 and NODAGA-PEG2-RM26. Methods: NOTA/NODAGA-PEG2-RM26 were labeled with 64Cu and evaluated in GRPR-expressing PC-3 cells. Biodistribution of [64Cu]Cu-NOTA/NODAGA-PEG2-RM26 was studied in PC-3 xenografted mice and compared to the biodistribution of [57Co]Co-NOTA/NODAGA-PEG2-RM26 at 3 and 24 h p.i. Preclinical PET/CT imaging was performed in tumor-bearing mice. NOTA/NODAGA-PEG2-RM26 were stably labeled with 64Cu with quantitative yields. In vitro, binding of [64Cu]Cu-NOTA/NODAGA-PEG2-RM26 was rapid and GRPR-specific with slow internalization. In vivo, [64Cu]Cu-NOTA/NODAGA-PEG2-RM26 bound specifically to GRPR-expressing tumors with fast clearance from blood and normal organs and displayed generally comparable biodistribution profiles to [57Co]Co-NOTA/NODAGA-PEG2-RM26; tumor uptake exceeded normal tissue uptake 3 h p.i.. Tumor-to-organ ratios did not increase significantly with time. [64Cu]Cu-NOTA-PEG2-RM26 had a significantly higher liver and pancreas uptake compared to other agents. 57Co-labeled radioconjugates showed overall higher tumor-to-non-tumor ratios, compared to the 64Cu-labeled counterparts. [64Cu]Cu-NOTA/NODAGA-PEG2-RM26 was able to visualize GRPR-expression in a murine PC model using PET. However, [55/57Co]Co-NOTA/NODAGA-PEG2-RM26 provided better in vivo stability and overall higher tumor-to-non-tumor ratios compared with the 64Cu-labeled conjugates.

68Ga-NeoB: Präklinische Ergebnisse zur Bildgebung gastrointestinaler Stromatumoren und zur Bestimmung der Zielrezeptordichte im Gastrointestinaltrakt

2021 ◽  
Vol 44 (02) ◽  
pp. 102-112
Author(s):  
Marc Pretze ◽  
Carmen Wängler ◽  
Stefan O. Schönberg ◽  
Björn Wängler
Keyword(s):  
Ex Vivo ◽  
Gastrointestinale Stromatumoren ◽  
Pet Ct ◽  
Grpr Antagonist

Zusammenfassung 68Ga-NeoB (früher bekannt als NeoBOMB1) ist ein neuartiger DOTA-gekoppelter Gastrin-Releasing-Peptid-Rezeptor(GRPR)-Antagonist mit hoher Bindungsaffinität zum GRPR und ausgezeichneter In-vivo-Stabilität. Ziel dieser präklinischen Studie war es, die Verwendung von 68Ga-NeoB zur Bestimmung der GRPR-Expression im Pankreasgewebe weiter zu erforschen, indem der GRPR-Sättigungsgrad im Pankreas bei der Verwendung verschiedener molarer Stoffmengen von 68Ga-NeoB geschätzt wurde. Darüber hinaus wurde 68Ga-NeoB als Tracer für gastrointestinale Stromatumoren (GIST) in 2 verschiedenen Mausstämmen untersucht. Anschließende Ex-vivo-Biodistributionsstudien mit verschiedenen Stoffmengen des antagonistischen Tracers 68Ga-NeoB mit hoher Bindungsaffinität zu GRPR wurden zur Abschätzung der Rezeptordichte in Organen oder Geweben mit hoher Expression dieses Rezeptors genutzt. Die Kombination von PET/CT und MRT-Datensätzen unterstützte die Ermittlung von Organanreicherungen auch bei Erreichen des Sättigungsgrades des Radiotracers in gastrointestinalen Organen.

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