Radiolabeled peptide conjugates for targeting of the bombesin receptor superfamily subtypes

Smith, Charles J.; Volkert, Wynn A.; Hoffman, Timothy J.

doi:10.1016/j.nucmedbio.2005.05.005

Cited by 171 publications

(223 citation statements)

References 34 publications

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“…Therefore the development of labeled Bn analogues for imaging or targeted cytotoxicity is a very active area of investigation at present. Numerous radiolabeled [ 111 Indium, 68 Gallium, 177 Lutetium, 64 Copper, 86 Yttrium, 18 F, 99m Tc] GRP analogues with enhanced stability that bind with high affinity to BB 2 -receptors are reported, as well as there ability to image various human tumors in vivo using gamma detectors or PET imaging [10,[69][70][71][72][73][74][75][76][77]. In some preliminary studies in humans, tumors were imaged in the majority of patients, and in some cases, tumors were detected using radiolabeled Bn analogues that were not seen on other commonly used imaging modalities [75,[78][79][80].…”

Section: Iiigbb Receptors-recent Advances-tumor Imaging and Receptomentioning

confidence: 99%

Bombesin-related peptides and their receptors: recent advances in their role in physiology and disease states

González

Moody

Igarashi

et al. 2008

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

186

175

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Purpose of review-Mammalian bombesin-related peptides, gastrin-releasing peptide(GRP) and neuromedin B(NMB) actions are mediated by two receptors (BB 1 -,BB 2 -receptor), which are closely related to the orphan receptor BRS-3(BB 3 -receptor).The purpose of this review is to highlight advances in the understanding of these peptides in physiology/disease states.Recent Findings-Pharmacologic/receptor-knockout studies showinvolvement of these receptors in a number of new processes/diseases. NMB/BB 1 -receptor is an important physiological regulator of pituitary-thyroid function; in mediating behavior, especially fear/anxiety; in mediating satiety through different cascades than GRP/BB 2 receptors and for its autocrine tumor-growth effects. GRP/ BB 2 -receptor plays important roles in: mediating signals for pruritus; lung development/injury; small intestinal mucosal defense and CNS processes such as learning/memory. The signaling mechanisms of its potent growth effects are being elucidate and possible therapeutic targets identified. BB 3 -receptor knockout mice provided insights for their obesity/glucose intolerance and demonstrate this receptor may be important in the lung response to injury, tumor growth and GI motility. Each receptor is frequently over-expressed in human tumors and have potent growth effects. This effect is being explored to develop new anti-tumor treatments, such as Bn-receptor ligands conjugated to cytotoxic agents.Summary-This receptor family are involved in an increasing number of CNS/peripheral processes physiologically and in disease states, and increased understanding of their role may lead to novel treatments, especially for pruritus, CNS disorders, lung diseases and tumor localization/treatment.

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Section: Iiigbb Receptors-recent Advances-tumor Imaging and Receptomentioning

confidence: 99%

Bombesin-related peptides and their receptors: recent advances in their role in physiology and disease states

González

Moody

Igarashi

et al. 2008

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

186

175

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“…3,23,24 To date, three mammalian BN receptor subtypes have been cloned and characterized: BB1, BB2 (GRPR) and BB3. 4,6 High affinity receptors for BN/GRP, specially GRPR overexpression, have been detected in specimens of prostate carcinoma 25 and PC-3 and DU-145 human prostate cancer cells. 4 We studied GRPR expression (mRNA and protein levels) through prostate cancer progression, because GRPR appears to be the most common receptor form in malignant prostate tissue 4,26 and BB1 and BB3 occur with much lower frequency.…”

Section: Discussionmentioning

confidence: 99%

“…4,5 Three receptor subtypes are found in mammalians: neuromedin B receptor subtype (BB1), GRP receptor subtype (GRPR subtype or BB2 subtype) and orphan receptor subtype (BB3). 6 BN-like peptides regulate the expression of multiple genes and intracellular signaling pathways, which together may enhance prostate cancer growth and metastasis. 7 High affinity receptors for BN/GRP and mRNA of the BN receptor subtype 2 have been found in androgen-dependent (LNCaP) and androgen-independent (PC-3 and DU-145) human prostate cancer cell lines.…”

mentioning

confidence: 99%

Regulation of HER expression and transactivation in human prostate cancer cells by a targeted cytotoxic bombesin analog (AN‐215) and a bombesin antagonist (RC‐3095)

Sotomayor

Muñoz-Moreno

Carmena

et al. 2010

Intl Journal of Cancer

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Bombesin (BN) and gastrin-releasing peptide (GRP) have been shown to stimulate the growth of human prostate cancer in vivo and in vitro by mechanisms initiated by binding of the peptide to BN/GRP receptor (GRPR). GRPR is overexpressed in a variety of human cancers, including human prostatic carcinoma. This led us to evaluate the effectiveness of blocking GRPR and of chemotherapy targeted to GRPR in androgen-dependent (LNCaP) and androgen-independent (PC-3) prostate cancer cells, which exhibit different features of disease progression. Thus, we used a cytotoxic BN/GRP analog, AN-215, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to BN-like carrier peptide, and a BN/GRP receptor antagonist, RC-3095. Semiquantitative RT-PCR and Western blotting revealed that mRNA and protein levels for GRPR increased in prostate cancer cells as compared with nonneoplastic RWPE-1 cells. Immunofluorocytochemistry and Western blot assays revealed that AN-215 was the most effective analog decreasing both the expression of epidermal growth factor receptor family members and the activation of epidermal growth factor receptor and HER-2, which are associated to a poor prognosis. Furthermore, analogs targeted to BN/GRP receptors, AN-215 and RC-3095, blocked the effect of BN on cell growth in RWPE-1, LNCaP and PC-3 cells. These findings shed light on the mechanisms of action of these analogs and support the view that the use of AN-215 and RC-3095 for blocking BN/GRP receptors for targeted therapy may be of benefit for treatment of advanced prostate cancer.Prostate carcinoma is the most common malignancy in men and the second leading cause of death from cancer. 1 Hormonal therapies based on androgen deprivation provide only a remission of limited duration, and patients with androgen refractory prostate cancer have a very poor prognosis. Treatment of advanced or metastatic cancers is carried out mainly by chemotherapy, which can also be applied as adjuvant to surgery and/or radiotherapy. 2 However, cancer chemotherapy is restricted by the toxicity of the drugs, and a more selective delivery of the cytotoxic agents to the tumors and their metastases would allow a dose escalation and reduce the peripheral toxicity. Targeted chemotherapy represents a modern oncologic strategy that improves the effectiveness of cytotoxic drugs and decreases their peripheral toxicity. 3 Bombesin (BN)-like peptides, such as gastrin-releasing peptide (GRP) and neuromedin B, bind to their specific Gprotein-coupled receptors (GPCRs) on the cell surface of tumors. 4,5 Three receptor subtypes are found in mammalians: neuromedin B receptor subtype (BB1), GRP receptor subtype (GRPR subtype or BB2 subtype) and orphan receptor subtype (BB3). 6 BN-like peptides regulate the expression of multiple genes and intracellular signaling pathways, which together may enhance prostate cancer growth and metastasis. 7 High affinity receptors for BN/GRP and mRNA of the BN receptor subtype 2 have been found in androgen-dependent (LNCaP) and androgen-independent (PC-3 and DU-145) hum...

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“…The C-terminal 7-14 amino acid sequence (GlnTrp-Ala-Val-Gly-His-Leu-Met-NH 2 ) of BN-like peptides is known to be critical for receptor binding affinity and biological activity (Smith, Volkert, Hoffman, 2005). Most radiolabeled BN-like peptides are based on the 7-14 amino acid sequence, coupled with a chelator through a spacer group at the N-terminus of the peptide (Smith, Volkert, Hoffman, 2005;Okarvi, 2004).…”

Section: Molecular Modelling and Cadd Applied To Development Of Radiomentioning

confidence: 99%

“…Most radiolabeled BN-like peptides are based on the 7-14 amino acid sequence, coupled with a chelator through a spacer group at the N-terminus of the peptide (Smith, Volkert, Hoffman, 2005;Okarvi, 2004). Also, much attention has been focused on developing 99m Tc-labeled BN-like pep-FIGURE 3 -Amino acid residue sequences for SST-14 and 111 In-OctreoScan (adapted from Okarvi, 2008), and the 3D structure of sandostatin retrieved from PDB entry code 1SOC (Melacini, 1997).…”

Section: Molecular Modelling and Cadd Applied To Development Of Radiomentioning

confidence: 99%

Polymeric micelles and molecular modeling applied to the development of radiopharmaceuticals

Grallert

Rangel-Yagui

Pasqualoto

et al. 2012

Braz. J. Pharm. Sci.

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Micelles composed of amphiphilic copolymers linked to a radioactive element are used in nuclear medicine predominantly as a diagnostic application. A relevant advantage of polymeric micelles in aqueous solution is their resulting particle size, which can vary from 10 to 100 nm in diameter. In this review, polymeric micelles labeled with radioisotopes including technetium (99mTc) and indium (111In), and their clinical applications for several diagnostic techniques, such as single photon emission computed tomography (SPECT), gamma-scintigraphy, and nuclear magnetic resonance (NMR), were discussed. Also, micelle use primarily for the diagnosis of lymphatic ducts and sentinel lymph nodes received special attention. Notably, the employment of these diagnostic techniques can be considered a significant tool for functionally exploring body systems as well as investigating molecular pathways involved in the disease process. The use of molecular modeling methodologies and computer-aided drug design strategies can also yield valuable information for the rational design and development of novel radiopharmaceuticals.
Micelas poliméricas compostas de copolímeros ligadas a um elemento radioativo são utilizadas em Medicina Nuclear com aplicação predominantemente diagnóstica. A vantagem relevante da utilização de micelas poliméricas em solução aquosa é o tamanho de suas partículas, as quais podem variar de 10 a 100 nm de diâmetro. Neste trabalho de revisão são apresentadas micelas poliméricas marcadas com radioisotopos, como tecnécio-99m (99mTc) e índio-111 (111In), assim como suas aplicações clínicas em técnicas de diagnóstico como Tomografia por emissão de Fóton Único (Single photon Emission Computed Tomography - SPECT), cintilografia, e Ressonância Magnética Nuclear (RMN). Neste contexto, sua aplicação em diagnóstico de sistema linfático e linfonodo sentinela recebe atenção especial. O emprego de técnicas de diagnóstico pode ser considerado uma ferramenta importante para a exploração de sistemas no organismo humano assim como para a investigação de caminhos moleculares envolvidos nos processos de diversas doenças. O uso de metodologias de modelagem molecular e estratégias de desenvolvimento de fármacos assistidas computacionalmente também pode fornecer informações valiosas para o planejamento e o desenvolvimento racional de novos radiofármacos

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Radiolabeled peptide conjugates for targeting of the bombesin receptor superfamily subtypes

Cited by 171 publications

References 34 publications

Bombesin-related peptides and their receptors: recent advances in their role in physiology and disease states

Bombesin-related peptides and their receptors: recent advances in their role in physiology and disease states

Regulation of HER expression and transactivation in human prostate cancer cells by a targeted cytotoxic bombesin analog (AN‐215) and a bombesin antagonist (RC‐3095)

Polymeric micelles and molecular modeling applied to the development of radiopharmaceuticals

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