Design and evaluation of radiolabeled tracers for tumor imaging

Wållberg, Helena; Ståhl, Stefan

doi:10.1002/bab.1111

Cited by 16 publications

(9 citation statements)

References 198 publications

(265 reference statements)

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“…Developing a nuclear tracer for the clinic requires in vitro characterization of the tracer, followed by in vivo assessment of its biodistribution and tumor targeting properties. To aid and accelerate this process, efforts are being made in order to develop in vitro and in vivo models, as well as imaging techniques for the preclinical setting [10]. One of such in vitro models is spheroids three-dimensional (3D) cell cultures.…”

Section: Introductionmentioning

confidence: 99%

Imaging of Tumor Spheroids, Dual-Isotope SPECT, and Autoradiographic Analysis to Assess the Tumor Uptake and Distribution of Different Nanobodies

et al. 2019

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Purpose Recent studies have shown rapid accumulation of nanobodies (NBs) in tumors and fast clearance of the unbound fraction, making NBs exceptional tracers for cancer imaging. In this study, we investigate the combination of in vitro imaging of tumor spheroids, in vivo dual-isotope single-photon emission computed tomography (SPECT), and ex vivo autoradiographic analysis of tumors to efficiently, and with few mice, assess the tumor uptake and distribution of different NBs. Procedures The irrelevant NB R2 (16 kDa) and the EGFR-targeted NBs 7D12 (16 kDa) and 7D12-R2 (32 kDa) were investigated. Confocal microscopy was used to study the penetration of the NBs into A431 tumor spheroids over time, using the anti-EGFR monoclonal antibody (mAb) cetuximab (150 kDa) as a reference. Dual-isotope [111In]DOTA-NB/[177Lu]DOTA-NB SPECT was used for longitudinal imaging of multiple tracers in the same animal bearing A431 tumor xenografts. Tumor sections were analyzed using autoradiography. Results No binding of the irrelevant NB was observed in spheroids, whereas for the specific tracers an increase in the spheroid’s covered area was observed over time. The NB 7D12 saturated the spheroid earlier than the larger, 7D12-R2. Even slower penetration was observed for the large mAb. In vivo, the tumor uptake of 7D12 was 19-fold higher than R2 after co-injection in the same animal, and 2.5-fold higher than 7D12-R2 when co-injected. 7D12-R2 was mainly localized at the rim of tumors, while 7D12 was found to be more evenly distributed. Conclusions This study demonstrates that the combination of imaging of tumor spheroids, dual-isotope SPECT, and autoradiography of tumors is effective in comparing tumor uptake and distribution of different NBs. Results were in agreement with published data, highlighting the value of monomeric NBs for tumor imaging, and re-enforcing the value of these techniques to accurately assess the most optimal format for tumor imaging. This combination of techniques requires a lower number of animals to obtain significant data and can accelerate the design of novel tracers.

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Section: Introductionmentioning

confidence: 99%

Imaging of Tumor Spheroids, Dual-Isotope SPECT, and Autoradiographic Analysis to Assess the Tumor Uptake and Distribution of Different Nanobodies

et al. 2019

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“…However, nuclear imaging itself provides poor information on morphological and anatomical features and call for the employment of specific tracers (i.e., imaging agents) able to emit γ-rays. 143 PET and SPECT are minimally invasive high-resolution techniques which enable quantitative estimation of the number of radio-labeled species available in a specific location. Both techniques are widely employed in early diagnosis and in the evaluation of patient response to therapy by exploiting radiolabeled markers.…”

Section: Conventional Imaging Techniquesmentioning

confidence: 99%

Section: Conventional Imaging Techniquesmentioning

confidence: 99%

Medical Imaging of Microrobots: Toward In Vivo Applications

et al. 2020

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Medical microrobots (MRs) have been demonstrated for a variety of non-invasive biomedical applications, such as tissue engineering, drug delivery, and assisted fertilization, among others. However, most of these demonstrations have been carried out in in vitro settings and under optical microscopy, being significantly different from the clinical practice. Thus, medical imaging techniques are required for localizing and tracking such tiny therapeutic machines when used in medical-relevant applications. This review aims at analyzing the state of the art of microrobots imaging by critically discussing the potentialities and limitations of the techniques employed in this field. Moreover, the physics and the working principle behind each analyzed imaging strategy, the spatiotemporal resolution, and the penetration depth are thoroughly discussed. The paper deals with the suitability of each imaging technique for tracking single or swarms of MRs and discusses the scenarios where contrast or imaging agent's inclusion is required, either to absorb, emit, or reflect a determined physical signal detected by an external system. Finally, the review highlights the existing challenges and perspective solutions which could be promising for future in vivo applications.

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“…As an advantage, ICG has a high photon count rate, but its depth of penetration is estimated to be between 2 and 4 cm [ 45 ], limiting its utility to imaging near the surface of the patients skin or patients undergoing surgery. There is a trend to shift from fluorescent imaging to radiolabeling targeting agents such as antibodies [ 46 ] to overcome this penetrance limitation. Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are the two majors molecular imaging modalities based on the detection of radioactive decay.…”

Section: Discussionmentioning

confidence: 99%

Early detection of pancreatic cancer in mouse models using a novel antibody, TAB004

Williams

Grover

et al. 2018

PLoS ONE

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Pancreatic ductal adenocarcinoma (PDA) is the fourth-leading cause of cancer death in the United States with a 5-year overall survival rate of 8% for all stages combined. But this decreases to 3% for the majority of patients that present with stage IV PDA at time of diagnosis. The lack of distinct early symptoms for PDA is one of the primary reasons for the late diagnosis. Common symptoms like weight loss, abdominal and back pains, and jaundice are often mistaken for symptoms of other issues and do not appear until the cancer has progressed to a late stage. Thus the development of novel imaging platforms for PDA is crucial for the early detection of the disease. MUC1 is a tumor-associated antigen (tMUC1) expressed on 80% of PDA. The goal of this study was to determine the targeting and detection capabilities of a tMUC1 specific antibody, TAB004. TAB004 antibody conjugated to a near infrared fluorescent probe was injected intraperitoneally into immune competent orthotopic and spontaneous models of PDA. Results show that fluorophore conjugated TAB004 specifically targets a) 1 week old small tumor in the pancreas in an orthotopic PDA model and b) very early pre-neoplastic lesions (PanIN lesions) that develop in the spontaneous PDA model before progression to adenocarcinoma. Thus, TAB004 is a promising antibody to deliver imaging agents directly to the pancreatic tumor microenvironment, significantly affecting early detection of PDA.

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Design and evaluation of radiolabeled tracers for tumor imaging

Cited by 16 publications

References 198 publications

Imaging of Tumor Spheroids, Dual-Isotope SPECT, and Autoradiographic Analysis to Assess the Tumor Uptake and Distribution of Different Nanobodies

Imaging of Tumor Spheroids, Dual-Isotope SPECT, and Autoradiographic Analysis to Assess the Tumor Uptake and Distribution of Different Nanobodies

Medical Imaging of Microrobots: Toward In Vivo Applications

Early detection of pancreatic cancer in mouse models using a novel antibody, TAB004

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