Review

Authors: Javad Garousi, Anna Orlova, Fredrik Y Frejd...

The use of radiolabelled antibodies was proposed in 1970s for staging of malignant tumours. Intensive research established chemistry for radiolabelling of proteins and understanding of factors determining biodistribution and targeting properties. The use of radioimmunodetection for staging of cancer was not established as common practice due to approval and widespread use of [F]-FDG, which provided a more general diagnostic use than antibodies or their fragments. Expanded application of antibody-based therapeutics renewed the interest in radiolabelled antibodies. RadioimmunoPET emerged as a powerful tool for evaluation of pharmacokinetics of and target engagement by biotherapeutics. In addition to monoclonal antibodies, new radiolabelled engineered proteins have recently appeared, offering high-contrast imaging of expression of therapeutic molecular targets in tumours shortly after injection. This creates preconditions for noninvasive determination of a target expression level and stratification of patients for targeted therapies. Radiolabelled proteins hold great promise to play an important role in development and implementation of personalised targeted treatment of malignant tumours. This article provides an overview of biodistribution and tumour-seeking features of major classes of targeting proteins currently utilized for molecular imaging. Such information might be useful for researchers entering the field of the protein-based radionuclide molecular imaging.

PubMed: 32577943
DOI: 10.1186/s41181-020-00094-w

Review

Authors: Suxia Han, Guihua Jin, Lijuan Wang...

PAM4, a new monoclonal antibody (MAb) known as clivatuzumab, is highly reactive with pancreatic cancer and precursor lesions. It is absent from the normal tissues and has limited reactivity with nonpancreatic cancer. The detailed characteristic of the PAM4 epitope is unknown but recent studies have shown that it is dependent on MUC1 glycosylation status. The limited PAM4 expression pattern makes it an attractive candidate for management of pancreatic adenocarcinoma. In addition, PAM4 is a serum biomarker for diagnosis of pancreatic cancer. Several different radiolabeled immunodiagnostic and immunotherapeutic agents of PAM4 have been developed and some are being evaluated in preclinical and/or clinical studies. The review will focus on PAM4 and its potential utility for the diagnosis, radioimmunodetection, and radioimmunotherapy of pancreatic cancer.

Topics: Animals; Antibodies, Monoclonal; Humans; Neoplasm Staging; Pancreatic Neoplasms; Precancerous Conditions; Radioimmunodetection; Radioimmunotherapy

PubMed: 24818166
DOI: 10.1155/2014/268479

Review

Authors: Carlos Pérez-Medina, Zahi A Fayad, Willem J M Mulder...

The immune system's role in atherosclerosis has long been an important research topic and is increasingly investigated for therapeutic and diagnostic purposes. Therefore, noninvasive imaging of hematopoietic organs and immune cells will undoubtedly improve atherosclerosis phenotyping and serve as a monitoring method for immunotherapeutic treatments. Among the available imaging techniques, positron emission tomography's unique features make it an ideal tool to quantitatively image the immune response in the context of atherosclerosis and afford reliable readouts to guide medical interventions in cardiovascular disease. Here, we summarize the state of the art in the field of atherosclerosis positron emission tomography immunoimaging and provide an outlook on current and future applications.

Topics: Atherosclerosis; Hematopoietic System; Humans; Nanoparticles; Phagocytes; Plaque, Atherosclerotic; Positron-Emission Tomography; Radioimmunodetection; Radiopharmaceuticals

PubMed: 32078338
DOI: 10.1161/ATVBAHA.119.313455

Review

Authors: Pontus K E Börjesson, Ernst J Postema, Remco de Bree...

Radiolabeled monoclonal antibodies (MAbs) can add a dimension to diagnostic imaging and staging of metastatic head and neck cancer, as well as in eradication of this disease. The vast majority of malignancies arising in the oral cavity, pharynx and larynx are squamous cell carcinomas. This common cellular origin makes it attractive to search for appropriate tumor-associated antigens, which are preferentially expressed in these neoplasms. Radiolabeled MAbs directed against these antigens can be used for tumor detection and selective therapy, known as radioimmunoscintigraphy and radioimmunotherapy, respectively. The combination of MAbs with positron emission tomography (PET) is an attractive novel option to improve tumor detection and to facilitate MAb quantification in a therapeutic setting. Basic aspects of tumor targeting with MAbs, as well as a review of the clinical trials reported in the literature, including own results, are presented.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Head and Neck Neoplasms; Humans; Lymphatic Metastasis; Neoplasm Metastasis; Neoplasm Staging; Radioimmunodetection; Radioimmunotherapy

PubMed: 15288829
DOI: 10.1016/j.oraloncology.2003.11.009

Review

Authors: Vilma I J Jallinoja, Jacob L Houghton

The principle of pretargeted radioimmunoimaging and therapy has been investigated over the past 30 y in preclinical and clinical settings with the aim of reducing the radiation burden of healthy tissue for antibody-based nuclear medicine techniques. In the past few decades, 4 pretargeting methodologies have been proposed, and 2 of them-the bispecific antibody-hapten and the streptavidin-biotin platforms-have been evaluated in humans in phase 1 and 2 studies. With this review article, we aim to survey clinical pretargeting studies in order to understand the challenges that these platforms have faced in human studies and to provide an overview of how the clinical approval of the pretargeting system has proceeded in the past several decades. Additionally, we will discuss the successes of the pretargeting human studies and compare and highlight the pretargeting approaches and conditions that will advance clinical translation of the pretargeting platform in the future.

Topics: Humans; Radioimmunotherapy; Neoplasms; Animals; Radioimmunodetection

PubMed: 34016727
DOI: 10.2967/jnumed.120.260687

Review

Authors: C Van de Wiele, H Revets, N Mertens...

The advent of biotechnology has made it possible to overcome the undesired host antiglobulin response evidenced following the injection of rodent antibodies for radioimmunoimaging; initially through the construction of chimeric and CDR-grafted antibodies and more recently through the derivation of completely human antibodies. Available platforms for derivation of completely human antibodies include phage- and ribosome-display techniques and transgenic mice that are deleted in their own antibody genes and reconstituted with large parts of the genes encoding for human antibodies. Additionally, biotechnology has made it possible to tailor affinity, respectively through CDR-walking or chain schuffling, and avidity, respectively through manifold engineering, of antibodies and derivatives. More recent developments include the development of highly stable single domain binders based on the use of a conserved framework region and a highly variable antigen-binding site, using other proteins or molecules that are smaller in size and easier to manufacture than antibodies. Finally, novel technologies have been and are being developed optimizing the concept of pretargeting.

Topics: Animals; Antibodies, Monoclonal; Humans; Neoplasms; Radioimmunodetection; Radioisotopes; Radiopharmaceuticals

PubMed: 15640795
DOI: No ID Found

Review

Authors: Tove Olafsen, Anna M Wu

Noninvasive molecular imaging approaches include nuclear, optical, magnetic resonance imaging, computed tomography, ultrasound, and photoacoustic imaging, which require accumulation of a signal delivered by a probe at the target site. Monoclonal antibodies are high affinity molecules that can be used for specific, high signal delivery to cell surface molecules. However, their long circulation time in blood makes them unsuitable as imaging probes. Efforts to improve antibodies pharmacokinetics without compromising affinity and specificity have been made through protein engineering. Antibody variants that differ in antigen binding sites and size have been generated and evaluated as imaging probes to target tissues of interest. Fast clearing fragments, such as single-chain variable fragment (scFv; 25 kDa), with 1 antigen-binding site (monovalent) demonstrated low accumulation in tumors because of the low exposure time to the target. Using scFv as building block to produce larger, bivalent fragments, such as scFv dimers (diabodies, 50 kDa) and scFv-fusion proteins (80 kDa minibodies and 105 kDa scFv-Fc), resulted in higher tumor accumulation because of their longer residence time in blood. Imaging studies with these fragments after radiolabeling have demonstrated excellent, high-contrast images in gamma cameras and positron emission tomography scanners. Several studies have also investigated antibody fragments conjugated to fluorescence (near infrared dyes), bioluminescence (luciferases), and quantum dots for optical imaging and iron oxides nanoparticles for magnetic resonance imaging. However, these studies indicate that there are several factors that influence successful targeting and imaging. These include stability of the antibody fragment, the labeling chemistry (direct or indirect), whether critical residues are modified, the number of antigen expressed on the cell, and whether the target has a rapid recycling rate or internalizes upon binding. The preclinical data presented are compelling, and it is evident that antibody-based molecular imaging tracers will play an important future role in the diagnosis and management of cancer and other diseases.

Topics: Antibodies, Monoclonal; Humans; Image Enhancement; Isotope Labeling; Molecular Probe Techniques; Radioimmunodetection; Radiopharmaceuticals; Tomography, Emission-Computed

PubMed: 20350626
DOI: 10.1053/j.semnuclmed.2009.12.005

Authors: P Holvoet, D Collen

Topics: Humans; Indium Radioisotopes; Radioimmunodetection; Thrombosis

PubMed: 1744723
DOI: No ID Found

Review

Authors: Françoise Kraeber-Bodéré, Caroline Rousseau, Caroline Bodet-Milin...

Labeled antibodies, as well as their fragments and antibody-derived recombinant constructs, have long been proposed as general vectors to target radionuclides to tumor lesions for imaging and therapy. They have indeed shown promise in both imaging and therapeutic applications, but they have not fulfilled the original expectations of achieving sufficient image contrast for tumor detection or sufficient radiation dose delivered to tumors for therapy. Pretargeting was originally developed for tumor immunoscintigraphy. It was assumed that directly-radiolabled antibodies could be replaced by an unlabeled immunoconjugate capable of binding both a tumor-specific antigen and a small molecular weight molecule. The small molecular weight molecule would carry the radioactive payload and would be injected after the bispecific immunoconjugate. It has been demonstrated that this approach does allow for both antibody-specific recognition and fast clearance of the radioactive molecule, thus resulting in improved tumor-to-normal tissue contrast ratios. It was subsequently shown that pretargeting also held promise for tumor therapy, translating improved tumor-to-normal tissue contrast ratios into more specific delivery of absorbed radiation doses. Many technical approaches have been proposed to implement pretargeting, and two have been extensively documented. One is based on the avidin-biotin system, and the other on bispecific antibodies binding a tumor-specific antigen and a hapten. Both have been studied in preclinical models, as well as in several clinical studies, and have shown improved targeting efficiency. This article reviews the historical and recent preclinical and clinical advances in the use of bispecific-antibody-based pretargeting for radioimmunodetection and radioimmunotherapy of cancer. The results of recent evaluation of pretargeting in PET imaging also are discussed.

PubMed: 25873896
DOI: 10.3389/fphar.2015.00054