RESUMO
ABSTRACT: Adrenocortical carcinoma (ACC) is a rare malignancy with a prevalence of 1 to 2 cases/million/year. The diagnosis depends upon endocrine workup followed by imaging with CT, MRI, and 18F-FDG PET/CT. The treatment includes surgical resection, debulking surgery, chemotherapy, and radiotherapy. However, patients do not respond well to any of the available therapies. We present noninvasive imaging of histopathology-proven ACC patients using 68Ga-DOTAGA-IAC PET/CT, specific for integrin αvß3. 68Ga-DOTAGA-IAC PET/CT 45 minutes after IV injection showed a decent tumor-to-background ratio and could be used as a promising radiotracer for metastatic and recurrent ACC.
Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Carcinoma Adrenocortical/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Neoplasias do Córtex Suprarrenal/diagnóstico por imagem , Neoplasias do Córtex Suprarrenal/patologia , Fluordesoxiglucose F18RESUMO
UNLABELLED: (68)Ga-NODAGA-THERANOST™ is an αvß3 integrin antagonist and the first radiolabeled peptidomimetic to reach clinical development for targeting integrin receptors. In this first-in-human study, the feasibility of integrin receptor peptidomimetic positron emission tomography/computed tomography (PET/CT) imaging was confirmed in patients with non-small-cell lung cancer and breast cancer. METHODS: Patients underwent PET/CT imaging with (68)Ga NODAGA-THERANOST. PET images were analyzed qualitatively and quantitatively and compared to 2-deoxy-2-((18)F) fluoro-d-glucose ((18)F-FDG) findings. Images were obtained 60 minutes postinjection of 300-500 MBq of (68)Ga-NODAGA-THERANOST. RESULTS: (68)Ga-NODAGA-THERANOST revealed high tumor-to-background ratios (SUVmax=4.8) and uptake at neoangiogenesis sites. Reconstructed fused images distinguished cancers with high malignancy potential and enabled enhanced bone metastasis detection. (18)F-FDG-positive lung and lymph node metastases did not show uptake, indicating the absence of neovascularization. CONCLUSIONS: (68)Ga-NODAGA-THERANOST was found to be safe and effective, exhibiting in this study rapid blood clearance, stability, rapid renal excretion, favorable biodistribution and PK/PD, low irradiation burden (µSv/MBq/µg), and convenient radiolabeling. This radioligand might enable theranostics, that is, a combination of diagnostics followed by the appropriate therapeutics, namely antiangiogenic therapy, image-guided presurgical assessment, treatment response evaluation, prediction of pathologic response, neoadjuvant-peptidomimetic-radiochemotherapy, and personalized medicine strategies. Further clinical trials evaluating (68)Ga-NODAGA-THERANOST are warranted.
Assuntos
Acetatos/administração & dosagem , Radioisótopos de Gálio/administração & dosagem , Compostos Heterocíclicos com 1 Anel/administração & dosagem , Integrina alfaVbeta3/antagonistas & inibidores , Neovascularização Patológica/tratamento farmacológico , Peptidomiméticos/uso terapêutico , Acetatos/metabolismo , Adulto , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Compostos Heterocíclicos com 1 Anel/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Distribuição Tecidual , Tomografia Computadorizada por Raios X/métodosRESUMO
There is growing interest in small peptidomimetic α(v)ß(3) integrin antagonists that are readily synthesized and characterized and can be easily handled using physiological conditions. Peptidomimetic 4-[2-(3,4,5,6-tetrahydropyrimidine-2-ylamino)ethyloxy]benzoyl-2-[N-(3-amino-neopenta-1-carbamyl)]-aminoethylsulfonyl-amino-ß-alanine (IAC) was successfully conjugated to 1-(1-carboxy-3-carbo-t-butoxypropyl)-4,7-(carbo-tert-butoxymethyl)-1,4,7-triazacyclononane (NODA-GA(tBu)(3)) and 1-(1-carboxy-3-carbotertbutoxymethyl)-1,4,7,10-tetraazacyclododecane (DOTA-GA(tBu)(4)) and radiolabeled with (111)In, (67)Ga and (203)Pb. Results of a radioimmunoassay demonstrated binding to purified α(v)ß(3) integrin when 1-4equiv of integrin were added to the reaction. Based on this promising result, investigations are moving forward to evaluate the NODA-GA-IAC and DOTA-GA-IAC conjugates for targeting tumor associated angiogenesis and α(v)ß(3) integrin positive tumors to define their PET and SPECT imaging qualities as well as their potential for delivery of therapeutic radionuclides.