Preparation of 68 Ga-labelled DOTA-peptides using a manual labelling approach for small-animal PET imaging

Romero, Eduardo; Martínez, A.; Oteo, Marta; García, Angel Manuel Orejana; Morcillo, Miguel A.

doi:10.1016/j.apradiso.2015.10.005

Cited by 10 publications

(9 citation statements)

References 50 publications

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“…The peptide DOTA-D-Phe1,Tyr3-octreotate (DOTA-TATE), a somatostatin analog, which has a high affinity for the SSTR2 subtype somatostatin receptor, was labeled with 68 Ga obtained from a 68 Ge/ 68 Ga radionuclide generator as previously described ( Romero et al, 2016 ).…”

Section: Methodsmentioning

confidence: 99%

A knockin mouse model for human ATP4aR703C mutation identified in familial gastric neuroendocrine tumors recapitulates the premalignant condition of the human disease and suggests new therapeutic strategies

Calvete

Varró

Pritchard

et al. 2016

Disease Models &Amp; Mechanisms

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By whole exome sequencing, we recently identified a missense mutation (p.R703C) in the human ATP4a gene, which encodes the proton pump responsible for gastric acidification. This mutation causes an aggressive familial type I gastric neuroendocrine tumor in homozygous individuals. Affected individuals show an early onset of the disease, characterized by gastric hypoacidity, hypergastrinemia, iron-deficiency anemia, gastric intestinal metaplasia and, in one case, an associated gastric adenocarcinoma. Total gastrectomy was performed as the definitive treatment in all affected individuals. We now describe the generation and characterization of a knockin mouse model for the ATP4aR703C mutation to better understand the tumorigenesis process. Homozygous mice recapitulated most of the phenotypical alterations that were observed in human individuals, strongly suggesting that this mutation is the primary alteration responsible for disease development. Homozygous mice developed premalignant condition with severe hyperplasia, dysplasia and glandular metaplasia in the stomach. Interestingly, gastric acidification in homozygous mice, induced by treatment with 3% HCl acid in the drinking water, prevented (if treated from birth) or partially reverted (if treated during adulthood) the development of glandular metaplasia and dysplasia in the stomach and partially rescued the abnormal biochemical parameters. We therefore suggest that, in this model, achlorhydria contributes to tumorigenesis to a greater extent than hypergastrinemia. Furthermore, our mouse model represents a unique and novel tool for studying the pathologies associated with disturbances in gastric acid secretion.

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Section: Methodsmentioning

confidence: 99%

A knockin mouse model for human ATP4aR703C mutation identified in familial gastric neuroendocrine tumors recapitulates the premalignant condition of the human disease and suggests new therapeutic strategies

Calvete

Varró

Pritchard

et al. 2016

Disease Models &Amp; Mechanisms

Self Cite

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“…In addition to its short half-life, a key advantage of 68 Ga or 44 Sc is that they can be produced from a commercially available 68 Ge/ 68 Ga or 44 Ti/ 44 Sc generator allowing their production to be cyclotron-independent, making it accessible to any PET center and at a lower economic cost [ 77 , 78 , 79 ]. With regards to 44 Sc, as it emits prompt gamma-rays right after the positron emission, it can be distinguished from standard positron emitters like 68 Ga or 18 F, enabling multiplexed PET (mPET) imaging [ 80 , 81 , 82 ].…”

Section: Novel Non-invasive Immunotargeted Imaging Methods For Pdamentioning

confidence: 99%

Diagnosis of Pancreatic Ductal Adenocarcinoma by Immuno-Positron Emission Tomography

González-Gómez

Pazo‐Cid

Sarria

et al. 2021

JCM

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Diagnosis of pancreatic ductal adenocarcinoma (PDAC) by current imaging techniques is useful and widely used in the clinic but presents several limitations and challenges, especially in small lesions that frequently cause radiological tumors infra-staging, false-positive diagnosis of metastatic tumor recurrence, and common occult micro-metastatic disease. The revolution in cancer multi-“omics” and bioinformatics has uncovered clinically relevant alterations in PDAC that still need to be integrated into patients’ clinical management, urging the development of non-invasive imaging techniques against principal biomarkers to assess and incorporate this information into the clinical practice. “Immuno-PET” merges the high target selectivity and specificity of antibodies and engineered fragments toward a given tumor cell surface marker with the high spatial resolution, sensitivity, and quantitative capabilities of positron emission tomography (PET) imaging techniques. In this review, we detail and provide examples of the clinical limitations of current imaging techniques for diagnosing PDAC. Furthermore, we define the different components of immuno-PET and summarize the existing applications of this technique in PDAC. The development of novel immuno-PET methods will make it possible to conduct the non-invasive diagnosis and monitoring of patients over time using in vivo, integrated, quantifiable, 3D, whole body immunohistochemistry working like a “virtual biopsy”.

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“…The labelled peptides were purified using a Sep-Pak Light C18 cartridge (Waters) conditioned and equilibrated previously with 4 mL of pure ethanol and 4 mL of deionized water. Thus, the reaction mixture was transferred onto Sep-Pak where the 68 Ga-DOTA-AF7p and colloidal 68 Ga were retained, whereas free 68 GaCl 3 passed through the cartridge [ 23 ]. Next, the cartridge was rinsed with 4 mL of deionized water, and the activity on the Sep-Pak cartridge was recovered with 0.5 mL ethanol 96% (v/v).…”

Section: Methodsmentioning

confidence: 99%

MT1-MMP as a PET Imaging Biomarker for Pancreas Cancer Management

Morcillo

Lucas

Oteo

et al. 2018

Contrast Media & Molecular Imaging

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Pancreatic ductal adenocarcinoma (PDAC) continues to be one of the deadliest cancers for which optimal diagnostic tools are still greatly needed. Identification of PDAC-specific molecular markers would be extremely useful to improve disease diagnosis and follow-up. MT1-MMP has long been involved in pancreatic cancer, especially in tumour invasion and metastasis. In this study, we aim to ascertain the suitability of MT1-MMP as a biomarker for positron emission tomography (PET) imaging. Two probes were assessed and compared for this purpose, an MT1-MMP-specific binding peptide (MT1-AF7p) and a specific antibody (LEM2/15), labelled, respectively, with 68Ga and with 89Zr. PET imaging with both probes was conducted in patient-derived xenograft (PDX), subcutaneous and orthotopic, PDAC mouse models, and in a cancer cell line (CAPAN-2)-derived xenograft (CDX) model. Both radiolabelled tracers were successful in identifying, by means of PET imaging techniques, tumour tissues expressing MT1-MMP although they did so at different uptake levels. The 89Zr-DFO-LEM2/15 probe showed greater specific activity compared to the 68Ga-labelled peptide. The mean value of tumour uptake for the 89Zr-DFO-LEM2/15 probe (5.67 ± 1.11%ID/g, n=28) was 25–30 times higher than that of the 68Ga-DOTA-AF7p ones. Tumour/blood ratios (1.13 ± 0.51 and 1.44 ± 0.43 at 5 and 7 days of 89Zr-DFO-LEM2/15 after injection) were higher than those estimated for 68Ga-DOTA-AF7p probes (of approximately tumour/blood ratio = 0.5 at 90 min after injection). Our findings strongly point out that (i) the in vivo detection of MT1-MMP by PET imaging is a promising strategy for PDAC diagnosis and (ii) labelled LEM2/15 antibody is a better candidate than MT1-AF7p for PDAC detection.

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Preparation of 68 Ga-labelled DOTA-peptides using a manual labelling approach for small-animal PET imaging

Cited by 10 publications

References 50 publications

A knockin mouse model for human ATP4aR703C mutation identified in familial gastric neuroendocrine tumors recapitulates the premalignant condition of the human disease and suggests new therapeutic strategies

A knockin mouse model for human ATP4aR703C mutation identified in familial gastric neuroendocrine tumors recapitulates the premalignant condition of the human disease and suggests new therapeutic strategies

Diagnosis of Pancreatic Ductal Adenocarcinoma by Immuno-Positron Emission Tomography

MT1-MMP as a PET Imaging Biomarker for Pancreas Cancer Management

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