RESUMEN
The new GnRH-Ιanalogue developed in this paper was based on the D-Trp6 -GnRH-Ι-scaffold, and its potency was increased by the replacement Gly-NH2 by NH-NH2 binding to the Gly at position 10. Triptorelin-Hydrazide analogue was synthesized using solid phase. For 111 In labeling, synthesized peptide was followed by conjugation with DOTA using pSCN-Bn-DOTA. The conjugated Triptorelin-Hydrazide was labeled with 500-550 MBq of 111 In-chloride (in 0.2 M HCl). At optimized conditions after labeling, radio-chromatography showed radiochemical purity of approximately equal to 98% (RTLC) and greater than 95% (HPLC). The serum stability of the tracer was determined up to 24 hr. Binding affinities of Triptorelin-Hydrazide analogue were determined in a binding assay for both human and rat GnRH receptors. For in vivo studies, 111 In-peptide was injected intravenously via the tail vein into rats and significant ovaries uptake consist with reported GnRH receptor mappings. In vitro radioligand binding assays performed with GnRHR-expressing human cell lines using 125 I-Triptorelin as the standard radioligand. The quantities of internalization efficiency and receptor affinity of the new radioligand were IC50 = 0.20 ± 0.04 nM vs 0.13 ± 0.08 nM for Triptorelin and internalization: 3.5 ± 0.9% at 1 hr and 12.8 ± 1.8% at 4 hr of the internal reference.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Hormona Liberadora de Gonadotropina/química , Hormona Liberadora de Gonadotropina/farmacología , Radioisótopos de Indio , Animales , Antineoplásicos/farmacocinética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Estabilidad de Medicamentos , Hormona Liberadora de Gonadotropina/farmacocinética , Compuestos Heterocíclicos con 1 Anillo/química , Humanos , Marcaje Isotópico , Ratones , Ratas , Distribución TisularRESUMEN
Paragangliomas associated with mutations of the SDHD gene can occasionally result in distant metastasis. Diagnosis can be difficult, and nuclear imaging is used to evaluate the case further. Not all tumors are alike; nuclear avidity may differ. We present a case in which metastatic paraganglioma caused by mutations of the SDHD gene was negative on 123I-metaiodobenzylguanidine scintigraphy and positive on 111In-labeled octreotide scintigraphy. This situation presents an opportunity for a novel therapeutic approach toward metastatic paraganglioma using targeted peptide receptor radionuclide therapy.
Asunto(s)
Imagen Multimodal , Paraganglioma/diagnóstico por imagen , Paraganglioma/patología , Femenino , Humanos , Persona de Mediana Edad , Mutación , Metástasis de la Neoplasia , Paraganglioma/genética , Succinato Deshidrogenasa/genéticaRESUMEN
PURPOSE: This study was performed to evaluate the efficacy of (177)Lu-labelled peptide receptor radionuclide therapy (PRRT) in patients with inoperable or metastatic neuroendocrine tumours (NETs). METHODS: Systematic searches of MEDLINE and EMBASE databases were performed using the keywords of "neuroendocrine", "(177)Lu" and "prognosis". All published studies of neuroendocrine tumours treated with (177)Lu-labelled radiopharmaceuticals and evaluated with either Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 or Southwest Oncology Group (SWOG) criteria or both were included. If there was more than one published study from the same institution, only one report with the information most relevant to this study was included. Each response criteria group was analysed for disease response rates and disease control rates, defined as the percentages of patients with complete response (CR) + partial response (PR), and CR + PR + stable disease (SD), respectively, to a therapeutic intervention in clinical trials of anticancer agents. The pooled proportions are presented with both a fixed-effects model and random-effects model. RESULTS: Six studies with 473 patients (4 in RECIST criteria group with 356 patients, 3 in SWOG criteria group with 375 patients and 1 in both groups) were included. The RECIST criteria group demonstrated disease response rates ranging between 17.6 and 43.8% with a pooled effect of 29% [95% confidence interval (CI) 24-34%]. Disease control rates ranged from 71.8 to 100%. The random-effects model showed an average disease control rate of 81% (95% CI 71-91%). The SWOG criteria group demonstrated disease response rates ranging between 7.0 and 36.5% with a pooled effect of 23% (95% CI 11-38%). Disease control rates ranged from 73.9 to 89.1%. The random-effects model showed an average disease control rate of 82% (95% CI 71-91%). CONCLUSION: (177)Lu-labelled PRRT is an effective treatment option for patients with inoperable or metastatic NETs.