The prototypes for tumor targeting with radiolabeled peptides are derivatives of somatostatin. Usually, they primarily have high affinity for somatostatin receptor subtype 2 (sst2), and they have moderate affinity for sst5. We aimed at developing analogs that recognize different somatostatin receptor subtypes for internal radiotherapy in order to extend the present range of accessible tumors. We synthesized DOTA-octapeptides based on octreotide by replacing Phe3 mainly with unnatural amino acids. The affinity profile was determined by using cell lines transfected with sst1-5. Internalization was determined by using AR42J, HEK-sst3, and HEK-sst5 cell lines, and biodistribution was studied in rat tumor models. Two of the derivatives thus obtained showed an improved binding affinity profile, enhanced internalization into cells expressing sst2 and sst3, respectively, and better tumor:kidney ratios in animals.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.chembiol.2006.08.012 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Are Oral Somatostatin Receptor Ligands Moving Closer to Becoming a Reality?
Clin Endocrinol (Oxf)
December 2024
Departments of Endocrinology, Leeds Centre for Diabetes & Endocrinology, Leeds Teaching Hospital NHS Trust, Leeds, UK.
With the current therapeutic modalities available to endocrinologists, control of GH and IGF-I is now possible in almost all patients with acromegaly with multi-modality therapy. Despite biochemical control of GH and IGF-I, patients with acromegaly continue to experience impaired quality of life. Although there are likely multiple factors contributing to this dissatisfaction with current medical therapies, in particular the widely utilised injectable long-acting somatostatin receptor ligands (iSRL), is a contributor.
View Article and Find Full Text PDFAnalysis of oxytocin and oxytocin receptor expressions after hand therapy treatment in a mouse model of chemotherapy-induced peripheral neuropathy .
Neuro Endocrinol Lett
December 2024
Di Bella Foundation, Via Guglielmo Marconi 51 Bologna, 40122 Italy.
Objectives: Triple negative breast cancer (TNBC) is a distinct subtype of breast cancer that has a poor prognosis due to the lack of effective therapeutic agents. Since a significant proportion of human surgical samples of TNBC expressed mRNA for the growth hormone (GH), growth hormone-releasing hormone (GHRH), and gonadotropin-releasing hormone (GnRH) receptors, and the mitogenic proliferative activity of GH, GHRH, and GnRH, have been identified as effective therapeutic targets for somatostatin and its analogs and GnRH analogs, Di Bella Method (DBM), a combination of hormonal analogs and vitamins, was introduced to target and inhibit solid tumors. The present study aimed to improve the prognosis of TNBC using DBM in women with TNBC.
View Article and Find Full Text PDFPasireotide-induced hyperglycemia in Cushing's disease and Acromegaly: A clinical perspective and algorithms proposal.
Front Endocrinol (Lausanne)
December 2024
Recordati Rare Diseases, Central and Eastern Europe, Warsaw, Poland.
Pasireotide is an effective treatment for both Cushing's disease (CD) and acromegaly due to its ability to suppress adrenocorticotropic hormone and growth hormone, and to normalize insulin-like growth factor-1 levels, resulting in tumor shrinkage. However, it may also cause hyperglycemia as a side effect in some patients. The aim of this study was to review previous recommendations regarding the management of pasireotide-induced hyperglycemia in patients with CD and acromegaly and to propose efficient monitoring and treatment algorithms based on recent evidence and current guidelines for type 2 diabetes treatment.
View Article and Find Full Text PDFPheochromocytoma: an updated scoping review from clinical presentation to management and treatment.
Front Endocrinol (Lausanne)
December 2024
One Health Research Group, Universidad de las Americas, Quito, Ecuador.
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from chromaffin cells, with 80-85% originating in the adrenal medulla and 15-20% from extra-adrenal chromaffin tissues (paragangliomas). Approximately 30-40% of PPGLs have a hereditary component, making them one of the most genetically predisposed tumor types. Recent advances in genetic research have classified PPGLs into three molecular clusters: pseudohypoxia-related, kinase-signaling, and -signaling pathway variants.
View Article and Find Full Text PDFBackground: Somatostatin analogs (SSAs) binding to and activating somatostatin receptors (SSTRs) have been extensively used for the treatment of neuroendocrine tumors (NETs). The currently approved synthetic SSAs have high affinity for SSTR2 (octreotide/lanreotide), or for SSTR2 and SSTR5 (pasireotide). These agents have shown symptoms control and antiproliferative effects in subsets of NET patients and this was associated to the expression of the targeted SSTRs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!