Peptides and Receptors in Image-Guided Therapy: Theranostics for Neuroendocrine Neoplasms
Section snippets
Peptides and SSTRs in NEN
A new avenue in the field of molecular imaging was opened in the late 1980s with the use of radiolabeled SMS analogs for the localization of NENs.5 There are 5 different types of SSTR proteins that have been cloned (SSTR 1-5); SSTR 2 consists of 2 subtypes, SSTR 2A and SSTR 2B. The basis of peptide receptor imaging using radiolabeled SMS analogs is the overexpression of some of these receptors in NENs, especially SSTR 2.6 The advantages of small peptides as compared with antibodies are better
SSTR PET/CT Using 68Ga
The single most imperative aspect of PET/CT is its ability to quantify the disease at a molecular level. For a quantitative approach, 68Ga and PET/CT is clearly superior to gamma-emitting radionuclides and single-photon emission CT (SPECT)/CT. The development of 68Ga-labeled SMS analogs has been a major breakthrough. 68Ga-DOTATOC was the first peptide that has been studied in a larger number of patients. 68Ga is a diagnostic trivalent radiometal with convenient labeling characteristics, and is
Diagnosis, Staging, and Restaging
In a recent study in normal human tissues, maximum standardized uptake value (SUVmax) of 68Ga-DOTATOC imaging has been related to the expression of SSTR 2 at the level of mRNA.31 This highly interesting observation shows the real power of molecular imaging. The novel normative database may improve diagnostics, monitoring, and therapy of SSTR-expressing tumors or inflammation on a molecular basis. Another recent study from our group by Kaemmerer et al provided for the first time the proof of
Peptide Receptor Radionuclide Therapy
Following the scintigraphic localization of NENs with radiolabeled SMS analogs, therapeutic approaches with radiolabeled peptides were developed. The biological basis of PRRNT is the receptor-mediated internalization and intracellular retention of the radiopeptide. PRRNT can deliver radiation doses to tumors, which are adequate to achieve volume reduction or even cure. Upregulation of SSTR 2 in the peritumoral vessels, but not in the distant vessels, may constitute another target for
Clinical Results of PRRNT
In a study including 265 patients with neuroendocrine gastroenteropancreatic or bronchial tumors, treatment with 177Lu-DOTATATE resulted not only in reduction of tumors and prolongation of overall survival but also improved the patients' self-assessed quality of life.67 In a milestone study including 310 patients with GEP NEN (published by the group from Erasmus Medical Center, Rotterdam), PRRNT with 177Lu-DOTATATE showed complete and partial tumor responses in 30% of the patients (with very
Theranostics of NENs With Other Peptides
The success of the theranostic approach in the management of NENs with SSTR targeting also prompted a case for exploring the possibility of targeting other peptide receptors like vasoactive intestinal peptide, cholecystokinin, and bombesin receptors.89, 90, 91 The expression of the following bombesin receptor subtypes has been demonstrated in NENs: gastrin-releasing peptide (GRP) receptors in gastrinomas, neuromedin-B in gut carcinoids, and BB3 in lung carcinoids. Of particular interest was the
References (98)
- et al.
Gastroenteropancreatic neuroendocrine tumors
Lancet Oncol
(2008) - et al.
Molecular imaging of neuroendocrine tumors
Semin Oncol
(2010) - et al.
Localisation of endocrine-related tumors with radioiodinated analogue of somatostatin
Lancet
(1989) - et al.
Imaging of neuroendocrine tumors
Semin Nucl Med
(2006) - et al.
Yttrium-90-labelled somatostatin-analogue for cancer treatment
Lancet
(1998) - et al.
Evaluation of positron emission tomography imaging using [68Ga]-DOTA-D Phe(1)-Tyr(3)-octreotide in comparison to [111In]-DTPAOC SPECTFirst results in patients with neuroendocrine tumors
Mol Imaging Biol
(2003) - et al.
Somatostatin receptors and their subtypes in human tumors and in peritumoral vessels
Metabolism
(1996) - et al.
Neuroendocrine neoplasia of the gastroentero systemPathology and classification
Onkologe
(2011) - et al.
ENETS Consensus guidelines for the standards of care in neuroendocrine tumors: Radiological examinations
Neuroendocrinology
(2009) - et al.
Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in man: Metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide
J Nucl Med
(1992)
DOTA-NOC, a high-affinity ligand of somatostatin receptor subtypes 2, 3 and 5 for labelling with various radiometals
Eur J Nucl Med Mol Imaging
Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands
Eur J Nucl Med Mol Imaging
Endocrine tumors of the gastrointestinal tract and pancreas
Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use
Eur J Nucl Med Mol Imaging
Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: The Rotterdam experience with more than 1000 patients
Eur J Nucl Med Mol Imaging
Oncology Committee of the EANM: 111In-pentetreotide scintigraphy: Procedure guidelines for tumour imaging
Eur J Nucl Med Mol Imaging
Detection of neuroendocrine tumors: 99mTc-P829 scintigraphy compared with 111In-pentetreotide scintigraphy
J Nucl Med
99mTc-HYNIC-[Tyr3]-octreotide for imaging somatostatin-receptor-positive tumors: Preclinical evaluation and comparison with 111In-octreotide
J Nucl Med
[99mTc]Demotate, a new 99mTc-based [Tyr3]octreotate analogue for the detection of somatostatin receptor-positive tumors: Synthesis and preclinical results
Eur J Nucl Med Mol Imaging
Evaluation of [99mTc/EDDA/HYNIC0]octreotide derivatives compared with [111In-DOTA0, Tyr3, Thr8]octreotide and [111In-DTPA0]octreotide: Does tumor or pancreas uptake correlate with the rate of internalization?
J Nucl Med
Gallium-67/gallium-68-[DFO]-octreotide—A potential radiopharmaceutical for PET imaging of somatostatin receptor-positive tumors: Synthesis and radiolabeling in vitro and preliminary in vivo studies
J Nucl Med
Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA0, d-Phe1, Tyr3]octreotide, a promising somatostatin analogue for radionuclide therapy
Eur J Nucl Med Mol Imaging
[177Lu-DOTA0 Tyr3]octreotate: Comparison with [111In-DTPAo]octreotide in patients
Eur J Nucl Med
Preclinical evaluation of new and highly potent analogues of octreotide for predictive imaging and targeted radiotherapy
Clin Cancer Res
68Ga-DOTANOC: A first compound for PET imaging with high affinity for somatostatin receptor subtypes 2 and 5
Eur J Nucl Med Mol Imaging
Biodistribution of the Ga-68 labeled somatostatin analogue DOTA-NOC in patients with neuroendocrine tumors: Characterization of uptake in normal organs and tumor lesions
Q J Nucl Med Mol Imaging
68Ga-labeled peptides in tumor imaging
J Nucl Med
First clinical evidence that imaging with somatostatin receptor antagonists is feasible
J Nucl Med
Generator-based PET radiopharmaceuticals for molecular imaging of tumors: On the way to THERANOSTICS
Dalton Trans
Processing of generator-produced 68Ga for medical application
J Nucl Med
Procedure guidelines for PET/CT tumor imaging with 68Ga-DOTA-conjugated peptides: 68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE
Eur J Nucl Med Mol Imaging
FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: Version 1.0
Eur J Nucl Med Mol Imaging
68Ga-DOTATOC PET/CT and somatostatin receptor (sst1-sst5) expression in normal human tissue: Correlation of sst2 mRNA and SUV max
Eur J Nucl Med Mol Imaging
Molecular imaging with 68Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumors
Eur J Nucl Med Mol Imaging
Biokinetics and imaging with the somatostatin receptor PET radioligand 68Ga-DOTATOC: Preliminary data
Eur J Nucl Med Mol Imaging
Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumors
Eur J Nucl Med Mol Imaging
68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: Comparison with somatostatin receptor scintigraphy and CT
J Nucl Med
Cost comparison of 111In-DTPA-octreotide scintigraphy and 68Ga-DOTATOC PET/CT for staging enteropancreatic neuroendocrine tumors
Eur J Nucl Med Mol Imaging
68Ga-DOTA-NOC PET/CT imaging of neuroendocrine tumors: Comparison with 111In-DTPA-octreotide (Octreoscan)
Mol Imaging Biol
A comparison of 68Ga-DOTATATE and 18F-FDG PET/CT in pulmonary neuroendocrine tumors
J Nucl Med
Concomitant lung and gastroenteropancreatic neuroendocrine tumors and the value of gallium-68 PET/CT
Cancer Imaging
Are radiogallium-labeled DOTA-conjugated somatostatin analogues superior to those labeled with other radiometals?
Eur J Nucl Med Mol Imaging
68Ga-DOTATOC versus 68Ga DOTATATE PET/CT in functional imaging of neuroendocrine tumors
J Nucl Med
The role of 68Ga-DOTATATE PET in patients with neuroendocrine tumors and negative or equivocal findings on 111In-DTPA-octreotide scintigraphy
J Nucl Med
68Ga-DOTANOC PET/CT clinical impact in patients with neuroendocrine tumors
J Nucl Med
Comparison of the pharmacokinetics of 68Ga-DOTATOC and 18F-FDG in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy
Eur J Nucl Med Mol Imaging
68 Ga-DOTA-TATE PET vs. 123I-MIBG in identifying malignant neural crest tumors
Mol Imaging Biol
Gluc-Lys([18F]FP)-TOCA PET in patients with SSTR-positive tumors: Biodistribution and diagnostic evaluation compared with [111In]DTPA-octreotide
J Nucl Med
Preparation and biological evaluation of copper-64-labeled tyr3-octreotate using a cross-bridged macrocyclic chelator
Clin Cancer Res
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2020, Nuclear Medicine and BiologyCitation Excerpt :natSc]Sc-DOTA-Ava-BBN2 displayed a three-fold higher binding affinity (IC50 = 5.2 ± 0.7 nM) than [68Ga]Ga-DOTA-Ava-BBN2 (IC50 = 15 ± 6 nM). This finding is in contrast to a recent study discussing a higher binding affinity of the natGa-DOTA bombesin BN [2–14] peptide compared to the corresponding natSc-DOTA peptide [21]. Regardless of using an Ava linker connecting the GRPR-binding peptide to the DOTA chelator in our peptides, the main difference in the previous study was the use of the BN [2–14] bombesin motif, which acts as a GRPR agonist rather than an antagonist as with our BBN2 motif [39,40].
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