RESUMO
A potential milestone in personalized nuclear medicine is theranostics of metastatic castration-resistant prostate cancer (mCRPC) based on molecular imaging using PET/CT with 68Ga-labeled prostate-specific membrane antigen (PSMA) ligands and molecular radiotherapy using PSMA-targeted radioligand therapy (PRLT) with 177Lu-PSMA ligands. 68Ga-PSMA PET/CT enables accurate detection of mCRPC lesions with high diagnostic sensitivity and specificity and provides quantitative and reproducible data that can be used to select patients for PRLT and therapeutic monitoring. Our comprehensive experience over the last 3 years using different radioligands indicates that PRLT is highly effective for the treatment of mCRPC, even in advanced cases, and potentially lends a significant benefit to overall and progression-free survival. Additionally, significant improvement in clinical symptoms and excellent palliation of pain can be achieved.
Assuntos
Carcinoma/radioterapia , Carcinoma/secundário , Glutamato Carboxipeptidase II/antagonistas & inibidores , Terapia de Alvo Molecular , Neoplasias de Próstata Resistentes à Castração/radioterapia , Radioisótopos/uso terapêutico , Antígenos de Superfície , Carcinoma/metabolismo , Medicina Baseada em Evidências , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/metabolismo , Radioisótopos/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION: For many tumors, the overexpression of the chemokine receptor CXCR4 is associated with increased malignancy and poor patient outcomes. However, comprehensive data for neuroendocrine neoplasms of the lung are still lacking. METHODS: CXCR4 expression was evaluated in a panel of bronchopulmonary neuroendocrine neoplasms (BP-NEN) comprising typical carcinoids (n = 26), atypical carcinoids (n = 30), and small cell lung cancers (SCLC, n = 34). Samples were analyzed by immunohistochemistry using the novel monoclonal rabbit anti-human CXCR4 antibody UMB-2 and by qRT-PCR. The expression was correlated with clinical data and overall patient survival. RESULTS: CXCR4 was predominantly localized at the plasma membrane of the tumor cells. CXCR4 was expressed with a high intensity in almost all of the 30 SCLC samples. In contrast, it was detected infrequently and with low intensity in the typical carcinoid and atypical carcinoid samples. There was a significant correlation between the immunohistochemistry and qRT-PCR data. Additionally, there was a significant negative relationship between CXCR4 expression and overall survival. CONCLUSIONS: With increasing malignancy, BP-NEN clearly differ in the extent of CXCR4 expression. As in other tumor entities, CXCR4 overexpression significantly correlates with negative patient outcome. Due to its particular high expression rate in SCLC, CXCR4 may serve as a promising new target for diagnostic and pharmacological intervention as well as for peptide receptor-based radionuclide therapy.
Assuntos
Biomarcadores Tumorais/análise , Tumor Carcinoide/imunologia , Neoplasias Pulmonares/imunologia , Receptores CXCR4/análise , Carcinoma de Pequenas Células do Pulmão/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Tumor Carcinoide/genética , Tumor Carcinoide/mortalidade , Tumor Carcinoide/patologia , Tumor Carcinoide/terapia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , RNA Mensageiro/análise , Receptores CXCR4/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia , Regulação para Cima , Adulto JovemRESUMO
CONTEXT AND OBJECTIVES: Gastroenteropancreatic neuroendocrine neoplasms are known for their overexpression of somatostatin receptors (SSTRs), which provide the molecular basis for diagnostic and therapeutic interventions. In contrast, few data on the SSTR expression profile exist for bronchopulmonary neuroendocrine neoplasms (BP-NEN). DESIGN AND SETTINGS: A total of 240 formalin-fixed, paraffin-embedded specimens from 26 typical carcinoid (TC), 30 atypical carcinoid (AC), and 34 small cell lung cancer (SCLC) patients were examined retrospectively by immunohistochemistry (IHC) using specific rabbit monoclonal antibodies and evaluated by the immunoreactive score. Adjacent slides from 20 samples of each tumor type were subjected to additional RT-quantitative PCR mRNA analysis. RESULTS: With different expression patterns, SSTRs were present in most of the tumor sections, at both the protein and mRNA levels. The RT-quantitative PCR data correlated with the IHC scores. SSTR1 was detected in approximately 65% of the TC and AC, but hardly in the SCLC, whereas both SSTR2A and SSTR5 were present in approximately 45% of each entity. Furthermore, the SSTR1 expression level was positively correlated with patient survival. CONCLUSIONS: Our results suggest that SSTRs can be used as novel diagnostic, prognostic, and therapeutic markers of BP-NEN. The differences in the SSTR expression profile between the three types of BP-NEN may help to set a diagnostic cutoff and predict patient prognosis. Similar to TC and AC, our results also revealed a previously unappreciated high level of SSTR2A expression in SCLC within a subgroup of patients. However, in most cases, pan-somatostatin analogs may represent an additional therapeutic option.
