Positron emission tomography (PET) imaging of neuroblastoma and melanoma with 64Cu-SarAr immunoconjugates.
نویسندگان
چکیده
The advancement of positron emission tomography (PET) depends on the development of new radiotracers that will complement (18)F-FDG. Copper-64 ((64)Cu) is a promising PET radionuclide, particularly for antibody-targeted imaging, but the high in vivo lability of conventional chelates has limited its clinical application. The objective of this work was to evaluate the novel chelating agent SarAr (1-N-(4-aminobenzyl)-3, 6,10,13,16,19-hexaazabicyclo[6.6.6] eicosane-1,8-diamine) for use in developing a new class of tumor-specific (64)Cu radiopharmaceuticals for imaging neuroblastoma and melanoma. The anti-GD2 monoclonal antibody (mAb) 14.G2a, and its chimeric derivative, ch14.18, target disialogangliosides that are overexpressed on neuroblastoma and melanoma. Both mAbs were conjugated to SarAr using carbodiimide coupling. Radiolabeling with (64)Cu resulted in >95% of the (64)Cu being chelated by the immunoconjugate. Specific activities of at least 10 microCi/microg (1 Ci = 37 GBq) were routinely achieved, and no additional purification was required after (64)Cu labeling. Solid-phase radioimmunoassays and intact cell-binding assays confirmed retention of bioactivity. Biodistribution studies in athymic nude mice bearing s.c. neuroblastoma (IMR-6, NMB-7) and melanoma (M21) xenografts showed that 15-20% of the injected dose per gram accumulated in the tumor at 24 hours after injection, and only 5-10% of the injected dose accumulated in the liver, a lower value than typically seen with other chelators. Uptake by a GD2-negative tumor xenograft was significantly lower (<5% injected dose per gram). MicroPET imaging confirmed significant uptake of the tracer in GD-2-positive tumors, with minimal uptake in GD-2-negative tumors and nontarget tissues such as liver. The (64)Cu-SarAr-mAb system described here is potentially applicable to (64)Cu-PET imaging with a broad range of antibody or peptide-based imaging agents.
منابع مشابه
A Pretargeted Approach for the Multimodal PET/NIRF Imaging of Colorectal Cancer
The complementary nature of positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging makes the development of strategies for the multimodal PET/NIRF imaging of cancer a very enticing prospect. Indeed, in the context of colorectal cancer, a single multimodal PET/NIRF imaging agent could be used to stage the disease, identify candidates for surgical intervention, and facil...
متن کاملThe effect of fasting on Positron Emission Tomography (PET) imaging
As a nuclear approach, Positron Emission Tomography (PET) is a functional imaging technique which is based on the detection of gamma ray pairs emitted by a positron-emitting radionuclide. There are certain limitations to this technique such as normal tissue uptake. Therefore, it has been recommended that patients prepare before scanning. Fasting for a short while before PET imaging is an exampl...
متن کاملCorrelation between positron emission tomography and Cerenkov luminescence imaging in vivo and ex vivo using 64Cu-labeled antibodies in a neuroblastoma mouse model
Antibody-based therapies gain momentum in clinical therapy, thus the need for accurate imaging modalities with respect to target identification and therapy monitoring are of increasing relevance. Cerenkov luminescence imaging (CLI) are a novel method detecting charged particles emitted during radioactive decay with optical imaging. Here, we compare Position Emission Tomography (PET) with CLI in...
متن کاملCalculation of Positron Distribution in the Presence of a Uniform Magnetic Field for the Improvement of Positron Emission Tomography (PET) Imaging Using GEANT4 Toolkit
Introduction Range and diffusion of positron-emitting radiopharmaceuticals are important parameters for image resolution in positron emission tomography (PET). In this study, GEANT4 toolkit was applied to study positron diffusion in soft tissues with and without a magnetic field for six commonly used isotopes in PET imaging including 11C, 13N, 15O, 18F, 68Ga, and 82Rb. Materials and Methods GEA...
متن کاملDetection of Alzheimer\\\\\\\'s Disease using Multitracer Positron Emission Tomography Imaging
Alzheimer's disease is characterized by impaired glucose metabolism and demonstration of amyloid plaques. Individual positron emission tomography tracers may reveal specific signs of pathology that is not readily apparent on inspection of another one. Combination of multitracer positron emission tomography imaging yields promising results. In this paper, 57 Alzheimer's disease neuroimaging ini...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 104 44 شماره
صفحات -
تاریخ انتشار 2007