RESUMEN
Natriuretic peptide system (NPS) is a group of peptide hormones or paracrine factors, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and natriuretic peptide precursor C (NPC), that are structurally related. The physiological effects of NPS include natriuresis, increased glomerular filtration rate, inhibition release of renin, vasopressin, and aldosterone, sympathetic inhibition, vasodilatations, and prevents cardiac hypertrophy and remodeling. ANP has immunological effects, as it is produced locally from immune cells; it regulates innate and adaptive immune responses. Metabolism and degradation of ANP are achieved by neutral endopeptidase (NEP), also known as neprilysin. Coronavirus disease 2019 (Covid-19) pandemic may lead to acute lung injury (ALI) and/or respiratory distress syndrome (ARDS). The underlying causes of inflammatory and immunological disorders in patients with severe Covid-19 are connected to the immune over-stimulation with the subsequent release of pro-inflammatory cytokines. Covid-19 severity is linked with high ANP serum levels regardless of acute cardiac injury. Inflammatory stimuli appear to be linked with the release of NPs, which anti-inflammatory effects prevent the development of ALI/ARDS in Covid-19. Therefore, neprilysin inhibitors like sacubitril increase endogenous NPs and may reduce the risk of ALI in Covid-19 due to the potentiation of endogenous anti-inflammatory effects of NPs. However, sacubitril increases gastrin-releasing peptide, cathepsin G and release of pro-inflammatory cytokines that are inactivated by neprilysin. In conclusion, NPs and neprilysin have cardio-pulmonary protective effects against Covid-19-induced ALI/ARDS. Neprilysin inhibitor sacubitril has dual protective and harmful effects regarding metabolizing vasoactive peptides by neprilysin. These findings require potential reevaluation of the effect of neprilysin inhibitors in managing Covid-19.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , Insuficiencia Cardíaca , Síndrome de Dificultad Respiratoria , Aldosterona , Aminobutiratos , Antiinflamatorios , Factor Natriurético Atrial/metabolismo , Factor Natriurético Atrial/uso terapéutico , Compuestos de Bifenilo , Catepsina G , Citocinas , Péptido Liberador de Gastrina/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Péptido Natriurético Encefálico/metabolismo , Péptido Natriurético Encefálico/uso terapéutico , Péptidos Natriuréticos , Neprilisina/metabolismo , Neprilisina/uso terapéutico , Renina/uso terapéutico , Tetrazoles/farmacología , Tetrazoles/uso terapéutico , Valsartán/uso terapéuticoRESUMEN
OBJECTIVES: The aim of this study was to evaluate the efficacy, safety, and tolerability of gastrin-releasing peptide (GRP) compared with placebo in autism spectrum disorder symptoms. METHODOLOGY: This is a randomized, double-blind, placebo-controlled crossover trial using GRP 160 pmol/kg for 4 consecutive days in 10 children with autism. Outcomes were measured by the Aberrant Behavior Checklist (ABC) scale. RESULTS: All participants were boys, aged between 4 and 9 years. There was a reduction in the scores of the ABC range and its subscales after use GRP and placebo. The reduction was more prominent with GRP, particularly in the subscale "hyperactivity and noncompliance," but there was no statistical difference between the results (P = 0.334). After a week of infusion, 5 children showed improvement of 25% or greater in the total score of the ABC scale with GRP use and 2 with placebo use; however, there was no statistical difference (P = 0.375). There were no adverse effects, changes in vital signs, or laboratory abnormalities associated with the use of GRP. CONCLUSIONS: The results of this study, despite the small sample size, reinforce previous data on the safety of the GRP in short-term use. There is a need for further research with other designs and a larger sample size to evaluate the efficacy and safety of GRP in children with autism.
Asunto(s)
Trastorno del Espectro Autista/tratamiento farmacológico , Conducta Infantil/efectos de los fármacos , Péptido Liberador de Gastrina/uso terapéutico , Psicotrópicos/uso terapéutico , Antiulcerosos/uso terapéutico , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Antipsicóticos/efectos adversos , Antipsicóticos/uso terapéutico , Trastorno del Espectro Autista/fisiopatología , Trastorno del Espectro Autista/psicología , Niño , Preescolar , Terapia Combinada/efectos adversos , Estudios Cruzados , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Método Doble Ciego , Quimioterapia Combinada/efectos adversos , Estudios de Seguimiento , Péptido Liberador de Gastrina/administración & dosificación , Péptido Liberador de Gastrina/efectos adversos , Humanos , Infusiones Intravenosas , Masculino , Omeprazol/uso terapéutico , Escalas de Valoración Psiquiátrica , Psicotrópicos/administración & dosificación , Psicotrópicos/efectos adversos , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
Neuronal gastrin-releasing peptide (GRP) has been proved to be an important neuromodulator in the brain and involved in a variety of neurological diseases. Whether GRP could attenuate cognition impairment induced by vascular dementia (VD) in rats, and the mechanism of synaptic plasticity and GRP's action on synaptic efficiency are still poorly understood. In this study, we first investigated the effects of GRP on glutamatergic transmission with patch-clamp recording. We found that acute application of GRP enhanced the excitatory synaptic transmission in hippocampal CA1 neurons via GRPR in a presynaptic mechanism. Secondly, we examined whether exogenous GRP or its analogue neuromedin B (NMB) could prevent VD-induced cognitive deficits and the mechanism of synaptic plasticity. By using Morris water maze, long-term potentiation (LTP) recording, western blot assay and immunofluorescent staining, we verified for the first time that GRP or NMB substantially improved the spatial learning and memory abilities in VD rats, restored the impaired synaptic plasticity and was able to elevate the expression of synaptic proteins, synaptophysin (SYP) and CaMKII, which play pivotal roles in synaptic plasticity. These results suggest that the facilitatory effects of GRP on glutamate release may contribute to its long-term action on synaptic efficacy which is essential in cognitive function. Our findings present a new entry point for a better understanding of physiological function of GRP and raise the possibility that GRPR agonists might ameliorate cognitive deficits associated with neurological diseases.
Asunto(s)
Trastornos del Conocimiento , Demencia Vascular/complicaciones , Péptido Liberador de Gastrina/uso terapéutico , Ácido Glutámico/metabolismo , Hipocampo/citología , Transmisión Sináptica/efectos de los fármacos , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , 6-Ciano 7-nitroquinoxalina 2,3-diona/uso terapéutico , Animales , Animales Recién Nacidos , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/prevención & control , Modelos Animales de Enfermedad , Estimulación Eléctrica , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Péptido Liberador de Gastrina/farmacología , Ácido Glutámico/farmacología , Técnicas In Vitro , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Red Nerviosa/efectos de los fármacos , Red Nerviosa/fisiología , Neuroquinina B/análogos & derivados , Neuroquinina B/farmacología , Neuroquinina B/uso terapéutico , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
OBJECTIVES: The aim of this study was to determine the efficacy and tolerability of gastrin-releasing peptide (GRP) for core symptoms of autism spectrum disorder. METHODS: This is a prospective, open-label study with 160 pmol/kg of GRP tested in 10 children with autism. Outcome measures used were the Clinical Global Impressions-Improvement Scale, Aberrant Behavior Checklist (ABC), Childhood Autism Rating Scale, and Autism Diagnostic Interview-Revised. Positive response was defined as a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions-Improvement Scale and an improvement of 25% or greater on at least 1 subscale of ABC. RESULTS: Six (60%) of the 10 subjects responded to GRP. Improvements were observed on the ABC irritability and hyperactivity subscales in 80% of patients, and 70% exhibited improvement on the social withdrawal subscale. On the Childhood Autism Rating Scale, there was a mean reduction of 4 points (4.3 ± 2.9). Analysis of the Autism Diagnostic Interview-Revised results detected significant improvements in the domain that assesses social interaction, with a mean reduction of 2.4 points (2.4 ± 2.83). Adverse effects occurred in 3 patients. CONCLUSIONS: Gastrin-releasing peptide was safe and well tolerated by most subjects and may be effective for core symptoms of autism.
Asunto(s)
Trastorno del Espectro Autista/tratamiento farmacológico , Péptido Liberador de Gastrina/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Masculino , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
How neuropeptides in the primate spinal cord regulate itch and pain is largely unknown. Here we elucidate the sensory functions of spinal opioid-related peptides and gastrin-releasing peptide (GRP) in awake, behaving monkeys. Following intrathecal administration, ß-endorphin (10-100 nmol) and GRP (1-10 nmol) dose-dependently elicit the same degree of robust itch scratching, which can be inhibited by mu-opioid peptide (MOP) receptor and GRP receptor (BB2) antagonists, respectively. Unlike ß-endorphin, which produces itch and attenuates inflammatory pain, GRP only elicits itch without affecting pain. In contrast, enkephalins (100-1000 nmol) and nociceptin-orphanin FQ (3-30 nmol) only inhibit pain without eliciting itch. More intriguingly, dynorphin A(1-17) (10-100 nmol) dose-dependently attenuates both ß-endorphin- and GRP-elicited robust scratching without affecting pain processing. The anti-itch effects of dynorphin A can be reversed by a kappa-opioid peptide (KOP) receptor antagonist nor-binaltorphimine. These nonhuman primate behavioral models with spinal delivery of ligands advance our understanding of distinct functions of neuropeptides for modulating itch and pain. In particular, we demonstrate causal links for itch-eliciting effects by ß-endorphin-MOP receptor and GRP-BB2 receptor systems and itch-inhibiting effects by the dynorphin A-KOP receptor system. These studies will facilitate transforming discoveries of novel ligand-receptor systems into future therapies as antipruritics and/or analgesics in humans.
Asunto(s)
Analgésicos Opioides/uso terapéutico , Péptido Liberador de Gastrina/uso terapéutico , Neuropéptidos/uso terapéutico , Dolor/tratamiento farmacológico , Prurito/tratamiento farmacológico , Médula Espinal/patología , Analgésicos Opioides/farmacología , Animales , Conducta Animal , Dinorfinas/farmacología , Femenino , Péptido Liberador de Gastrina/administración & dosificación , Péptido Liberador de Gastrina/farmacología , Hiperalgesia/tratamiento farmacológico , Inyecciones Espinales , Macaca mulatta , Masculino , Neuropéptidos/farmacología , Dolor/complicaciones , Prurito/complicaciones , Médula Espinal/efectos de los fármacos , betaendorfina/metabolismoRESUMEN
Recent studies support roles for neurokinin-1 (NK-1) and gastrin-releasing peptide (GRP) receptor-expressing spinal neurons in itch. We presently investigated expression of substance P (SP) and GRP in pruritogen-responsive primary sensory neurons and roles for these neuropeptides in itch signaling. Responses of dorsal root ganglion (DRG) cells to various pruritogens were observed by calcium imaging. DRG cells were then processed for SP, GRP, and isolectin B-4 (IB4; a marker for nonpeptidergic neurons) immunofluorescence. Of pruritogen-responsive DRG cells, 11.8-26.8%, 21.8-40.0%, and 21.4-26.8% were immunopositive for SP, GRP, and IB4, respectively. In behavioral studies, both systemic and intrathecal administration of a NK-1 receptor antagonist significantly attenuated scratching evoked by chloroquine and a protease-activated receptor 2 agonist, SLIGRL, but not histamine, bovine adrenal medulla peptide 8-22 (BAM8-22), or serotonin. Systemic or intrathecal administration of a GRP receptor antagonist attenuated scratching evoked by chloroquine and SLIGRL but not BAM8-22 or histamine. The GRP receptor antagonist enhanced scratching evoked by serotonin. These results indicate that SP and GRP expressed in primary sensory neurons are partially involved as neurotransmitters in histamine-independent itch signaling from the skin to the spinal cord.
Asunto(s)
Péptido Liberador de Gastrina/metabolismo , Prurito/metabolismo , Células Receptoras Sensoriales/metabolismo , Sustancia P/metabolismo , Animales , Calcio/metabolismo , Cloroquina/farmacología , Ganglios Espinales/metabolismo , Péptido Liberador de Gastrina/uso terapéutico , Histamina/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Antagonistas del Receptor de Neuroquinina-1 , Oligopéptidos/farmacología , Fragmentos de Péptidos/farmacología , Prurito/inducido químicamente , Prurito/tratamiento farmacológico , Receptores de Bombesina/antagonistas & inhibidores , Células Receptoras Sensoriales/efectos de los fármacos , Serotonina/farmacología , Transducción de Señal/efectos de los fármacos , Sustancia P/uso terapéuticoRESUMEN
Optimization of therapy for individual patients remains a goal of clinical practice. Radionuclide imaging can identify those patients who may benefit from subsequent targeted therapy by providing regional information on the distribution of the target. An ideal situation may be when the imaging and the therapeutic compounds are the same agent. Two antibodies ([ [90Y]ibritumomab, [131I]tositumomab) are now approved for the systemic radiotherapy of non-Hodgkin's lymphoma. The main hurdle is to deliver higher absorbed doses to the more refractory solid tumors paying particular regard to the bone marrow toxicity. The low dose is thought to be a result of the large size of antibodies slowing delivery to the target. Peptides having high affinity to receptors expressed on cancer cells are a promising alternative. They are usually rapidly excreted from the body through renal and/or hepatobiliary excretion thus creating a prolonged accumulation of the radioactivity in the kidneys, which represents a recognized issue for systemic radiotherapy. The first radiopeptide developed was a somatostatin analogue, which led to a major breakthrough in the field. Beside the kidney issue, somatostatin use remains limited to few cancers that express receptors in sufficiently large quantities, mainly neuroendocrine tumors. The gastrin releasing peptide (GRP) receptor is an attractive target for development of new radiopeptides with diagnostic and therapeutic potential. This is based upon the functional expression of GRP receptors in several of the more prevalent cancers including prostate, breast, and small cell lung cancer. This review covers the efforts currently underway to develop new and clinically promising GRP-receptor specific molecules labeled with imageable and therapeutic radionuclides.
Asunto(s)
Péptido Liberador de Gastrina/análogos & derivados , Péptido Liberador de Gastrina/uso terapéutico , Lutecio/farmacocinética , Lutecio/uso terapéutico , Neoplasias/metabolismo , Neoplasias/radioterapia , Receptores de Bombesina/metabolismo , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Humanos , Neoplasias/diagnóstico por imagen , Radioisótopos/farmacocinética , Radioisótopos/uso terapéutico , Cintigrafía , Radiofármacos/farmacocinética , Radiofármacos/uso terapéuticoRESUMEN
El péptido bombesina (BN), de 14 amino ácidos, se aisló de la piel de los batracios y forma parte de un amplio grupo de neuropéptidos con diversas funciones biológicas. El homólogo equivalente en los mamíferos es el péptido liberador de la gastrina (GRP) y sus receptores (GRP-r) se expresan abundantemente en la membrana de las células tumorales, estimulando su crecimiento. La unión BN-GRP-r es una fuerte unión altamente específica por lo cual la BN marcada con radionucleidos se ha utilizado en medicina nuclear para la localización de tumores malignos de cáncer de mama y próstata principalmente. Las modificaciones en la cadena peptídica y el marcado se llevan a cabo en la región de extremo-N inicial, quedando el extremo C-terminal con su especificidad y acción biológica intactas. Se presentan varios análogos de BN radiactivos y la estructura de uno nuevo formado por un conjugado EDDA/HYNIC-BBN que fácilmente se une al 99mTc. Las expectativas para utilizar radiofármacos de BN marcados con emisores beta-negativos en radiopéptidoterapia son grandes y prometedoras.
Asunto(s)
Humanos , Bombesina/análogos & derivados , Bombesina/farmacología , Péptido Liberador de Gastrina/análogos & derivados , Péptido Liberador de Gastrina/farmacología , Receptores de Bombesina/metabolismo , Bombesina , Bombesina/uso terapéutico , Datos de Secuencia Molecular , Neoplasias/diagnóstico , Neoplasias/radioterapia , Péptido Liberador de Gastrina , Péptido Liberador de Gastrina/uso terapéutico , Radiofármacos , Radiofármacos/uso terapéutico , Relación Estructura-ActividadRESUMEN
The discoverers of secretin already thought of the existence of a chemical excitant for the internal secretion of the pancreas. Numerous experiments have been performed and published between 1906 and 1935 testing the effect of injected or ingested duodenal ("secretin") extracts on fasting or elevated blood glucose levels of normal or diabetic animals and humans with contradictory results. In 1940, after a series of negative dog experiments performed by an opinion leader, the existence of an incretin was considered questionable and further research stopped for more than 20 years. However, after the development of the radio-immunoassay, the incretin-concept has been revived in 1964, showing that significantly more insulin was released after ingestion of glucose than after intravenous injection. The possibility that nerves or one of the known gut hormones were responsible for the incretin effect could be ruled out. In 1970, glucose dependent insulinotropic polypeptide (GIP), and finally, in 1985 glucagon-like peptide 1 (GLP-1) and its truncated form GLP-1(7-36) were recognized as true incretins. Thereafter, multiple antidiabetic qualities and the therapeutic perspectives of GLP-1(7-36) and its analogues and mimetics have been demonstratred.
Asunto(s)
Polipéptido Inhibidor Gástrico/historia , Glucagón/historia , Hipoglucemiantes/historia , Fragmentos de Péptidos/historia , Precursores de Proteínas/historia , Animales , Diabetes Mellitus/tratamiento farmacológico , Polipéptido Inhibidor Gástrico/uso terapéutico , Péptido Liberador de Gastrina/historia , Péptido Liberador de Gastrina/uso terapéutico , Hormonas Gastrointestinales/historia , Hormonas Gastrointestinales/uso terapéutico , Glucagón/uso terapéutico , Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/metabolismo , Secreción de Insulina , Fragmentos de Péptidos/uso terapéutico , Péptidos/historia , Péptidos/farmacología , Precursores de Proteínas/uso terapéutico , Secretina/uso terapéuticoRESUMEN
BACKGROUND: Gastric cancer is the fourth most common malignancy worldwide. Adenoviral vectors (Ads) have been applied for gene therapy of various cancers because of their high transduction efficiency. However, the infectivity of gastrointestinal cancer cells is poor due to the limited expression of the Coxsackie-adenovirus receptor (CAR). In addition, few tumor-specific promoters (TSPs) have been characterized for this type of cancer. To overcome these problems, we proposed TSP-driven conditionally replicating adenoviruses (CRAds) with fiber modification for virotherapy of gastric cancer. METHODS: We assessed the expression profile of eight TSPs in gastric cancer cell lines and evaluated promising candidates in the context of CRAd cytocidal effect. Next, infectivity enhancement by fiber modifications was analyzed in the gastric cancer cell lines. Finally, we combined the TSP-driven CRAds of choice with the fiber modifications to augment the killing effect. RESULTS: Out of the eight TSPs, the midkine (MK) and cyclooxygenase-2 (Cox-2M and Cox-2L) promoters showed high transcriptional activity in gastric cancer cells. When these promoters were used in a CRAd context, Cox-2 CRAds elicited the strongest cytocidal effect. The greatest infectivity enhancement was observed with adenoviral vectors displaying 5/3 chimeric fibers. Likewise, Cox-2 CRAds with 5/3 chimeric fibers showed the strongest cytocidal effect in gastric cancer cell lines. Therefore, Cox-2 CRAds with 5/3 chimeric fiber modification showed good selectivity and infectivity in gastric cancer cells to yield enhanced oncolysis. CONCLUSIONS: Cox-2 CRAds with 5/3 chimeric fiber modification are promising for virotherapy of gastric cancer.
Asunto(s)
Elementos de Facilitación Genéticos/genética , Vectores Genéticos/genética , Vectores Genéticos/uso terapéutico , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Adenoviridae/efectos de los fármacos , Adenoviridae/fisiología , Línea Celular Tumoral , Proteína de la Membrana Similar al Receptor de Coxsackie y Adenovirus , Ciclooxigenasa 2/efectos de los fármacos , Ciclooxigenasa 2/genética , Citocinas/efectos de los fármacos , Citocinas/genética , Elementos de Facilitación Genéticos/efectos de los fármacos , Péptido Liberador de Gastrina/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Regulación Viral de la Expresión Génica/efectos de los fármacos , Regulación Viral de la Expresión Génica/genética , Vectores Genéticos/efectos de los fármacos , Humanos , Integrinas/biosíntesis , Integrinas/efectos de los fármacos , Integrinas/genética , Midkina , Viroterapia Oncolítica , Regiones Promotoras Genéticas/efectos de los fármacos , Regiones Promotoras Genéticas/genética , Proteínas Inhibidoras de Proteinasas Secretoras , Proteínas/uso terapéutico , Receptores Virales/biosíntesis , Receptores Virales/efectos de los fármacos , Receptores Virales/genética , Inhibidores de Serina Proteinasa/uso terapéutico , Neoplasias Gástricas/virología , Transcripción Genética/efectos de los fármacos , Transcripción Genética/genética , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Replicación Viral/efectos de los fármacos , Replicación Viral/genéticaRESUMEN
Work on cytotoxic analogs of luteinizing hormone-releasing hormone (LH-RH), somatostatin and bombesin, designed for targeting chemotherapy to peptide receptors on various cancers, is reviewed here as the project is at advanced stages of development and clinical trials are pending. Cytotoxic analogs of LH-RH, AN-152 and AN-207, containing doxorubicin (DOX) or 2-pyrrolino-DOX (AN-201), respectively, target LH-RH receptors and can be used for the treatment of prostatic, breast, ovarian and endometrial cancers and melanomas. AN-201 was also incorporated into the cytotoxic analog of somatostatin, AN-238, which can be targeted to receptors for somatostatin in prostatic, renal, mammary, ovarian, gastric, colorectal and pancreatic cancers as well as glioblastomas and lung cancers, suppressing the growth of these tumors and their metastases. A cytotoxic analog of bombesin AN-215, containing 2-pyrrolino-DOX, was likewise synthesized and successfully tested in experimental models of prostate cancer, small cell lung carcinoma, gastrointestinal cancers and brain tumors expressing receptors for bombesin/gastrin-releasing peptide. This new class of targeted cytotoxic peptide analogs might provide a more effective therapy for various cancers.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Receptores de Superficie Celular/efectos de los fármacos , Animales , Bombesina/análogos & derivados , Bombesina/uso terapéutico , Péptido Liberador de Gastrina/análogos & derivados , Péptido Liberador de Gastrina/uso terapéutico , Hormona Liberadora de Gonadotropina/análogos & derivados , Hormona Liberadora de Gonadotropina/uso terapéutico , Humanos , Somatostatina/análogos & derivados , Somatostatina/uso terapéuticoRESUMEN
Small neuropeptides, labeled with gamma- and/or beta-emitting radionuclides, are currently being investigated for their ability to bind to cell-surface receptors, overexpressed in a wide variety of malignant tissues being, thus, potentially useful for radionuclide detection and/or therapy for tumors. Particular attention has been focused on the amphibian peptide, bombesin (BN), and the molecularly related gastrin-releasing peptide (GRP). These peptides act as neurotransmitters and endocrine cancer cell-growth factors on normal tissues as well as on neoplastic cells of various origin. In recent investigations, modification of the native peptide structure has been attempted in order to obtain derivatives, which might easily be labeled with radionuclides. Thus, iodinated (I-125) BN derivatives, as well as Indium (In-111) labeled BN analogs are currently being investigated, presenting satisfactory tumor localization. Also, some new BN analogs containing a 6-carbon linker have been prepared and labeled with Rhenium-188, resulting in positive in vitro binding to prostate cancer cells. More recent studies refer to the Technetium-99m labeling of BN, performed either directly, after attaching proper technetium-chelating groups onto the BN sequence, or indirectly, by coupling BN to a preformed 99mTc-tagging ligand. Both types of conjugates were found to have a high in vitro affinity for cells with BN receptors, also presenting satisfactory in vivo uptake in experimental tumor models. Pilot clinical studies of a new BN-derived, 99mTc-labeled pentadecapeptide indicated significant uptake by breast cancer and invaded lymph nodes, as well as by prostate cancer, small-cell lung carcinoma, gastro-entero-pancreatic tumors, and others, Further studies of this new GRP derivative, as well as of other new BN-like peptides, are intensively performed internationally today.