Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P61278 (
somatostatin
)
22,083
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Most of the radiolabeled
somatostatin
analogues (SSAs) are specific for subtype somatostatin receptor 2 (SSTR
2
). Lack of ligands targeting other subtypes of SSTRs, especially SSTR
1,
SSTR
3
, and SSTR
5
, limited their applications in tumors of low SSTR
2
expression, including lung tumor. In this study, we aimed to design and synthesize a positron emission tomography (PET) radiotracer targeting multi-subtypes of SSTRs for PET imaging.
PA1
peptide and its conjugate with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator or fluorescein isothiocyanate (FITC) at the N-terminal of the lysine position were synthesized.
68
Ga was chelated to DOTA-
PA1
to obtain
68
Ga-DOTA-
PA1
radiotracer. The stability, lipophilicity, binding affinity, and binding specificity of
68
Ga-DOTA-
PA1
and FITC-
PA1
were evaluated by various in vitro experiments. Micro-PET imaging of
68
Ga-DOTA-
PA1
was performed in nude mice bearing A549 lung adenocarcinoma, as compared with
68
Ga-DOTA-(Tyr3)-octreotate (
68
Ga-DOTA-TATE). Histological analysis of SSTR expression in A549 tumor tissues and human tumor tissues was conducted using immunofluorescence staining and immunohistochemical assay.
68
Ga-DOTA-
PA1
had high radiochemical yield and radiochemical purity of over 95% and 99%, respectively. The radiotracer was stable in vitro in different buffers over a 2 h incubation period. Cell uptake of
68
Ga-DOTA-
PA1
was 1.31-, 1.33-, and 1.90-fold that of
68
Ga-DOTA-TATE, which has high binding affinity only for SSTR
2
, after 2 h incubation in H520, PG, and A549 lung cancer cell lines, respectively. Micro-PET images of
68
Ga-DOTA-
PA1
showed that the PET imaging signal correlated with the total expression of SSTRs, instead of SSTR
2
only, which was measured by Western blotting and immunofluorescence analysis in mice bearing A549 tumors. In summary, a novel PET radiotracer,
68
Ga-DOTA-
PA1
, targeting multi-subtypes of SSTRs, was successfully synthesized and was confirmed to be useful for PET imaging. It may have potential as a noninvasive PET radiotracer for imaging SSTR-positive tumors.
...
PMID:Design, Synthesis, and Biological Evaluation of
68
Ga-DOTA-PA1 for Lung Cancer: A Novel PET Tracer for Multiple Somatostatin Receptor Imaging. 2927 11
64
Cu-labeled new pan-
somatostatin
receptors (pan-SSTRs) probe
PA1
was synthesized, characterized, and evaluated by
in vitro
and
in vivo
experiments. [
64
Cu]NOTA-
PA1
was obtained with high specific activity, high radiochemical purity, and good stability. Cell uptake of [
64
Cu]NOTA-
PA1
was higher than that of [
64
Cu]DOTA-TATE in MCF-7, A549, BGC823, and HT-29 cell lines. [
64
Cu]NOTA-
PA1
showed high binding affinity for SSTRs expressed in A549 cells. The
in vivo
biodistribution and micropositron emission tomography (micro-PET) imaging studies of [
64
Cu]NOTA-
PA1
revealed good detection ability in MCF-7 and A549 xenografted nude mice. The radiosynthesis, quality control, and preliminary biological evaluation of [
64
Cu]NOTA-
PA1
have broaden the application of radiolabeled octreotide for SSTRs imaging, which could act as a potential multisubtypes targeted radiotracer for imaging SSTRs-positive tumors.
...
PMID:Evaluation of Pan-SSTRs Targeted Radioligand [
64
Cu]NOTA-PA1 Using Micro-PET Imaging in Xenografted Mice. 3229 48
