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Radionuclide-based Diagnosis and Therapy of Prostate Cancer
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Sven-Erik Strand, Mohamed Altai, Joanna Strand, David Ulmert
Beta-emitting radionuclides usually have a long path length (<12 mm) and low linear energy transfer (LET) (≈0.2 keV/µm), supporting their therapeutic effectiveness in medium to large tumours. The long β-particle range is advantageous in heterogeneous tumours as the effect expands to distant located cells, even if not targeted directly (crossfire effect). However, the crossfire effect can also result in the irradiation of healthy tissue surrounding the tumour site (i.e. bone metastases and bone marrow). For example, in targeted radioimmunotherapy using antibodies as targeting vectors and β-emitters, bone-marrow toxicity represents one of the most common side effects due to non-specific irradiation of hematopoietic stem cells as a result of the prolonged circulation of the radionuclide-carrying antibodies in the blood.
Breast Imaging with Radiolabeled Antibodies
Published in Raymond Taillefer, Iraj Khalkhali, Alan D. Waxman, Hans J. Biersack, Radionuclide Imaging of the Breast, 2021
Lamk M. Lamki, Bruce J. Barron
When the ideal radioimmunoconjugate that localizes in high concentration in a large percentage of tumors is identified, the potential for radioimmunotherapy will become compelling. Radioimmunoimaging will play a crucial role in determining eligibility for radioimmunotherapy and for determining dosimetry. Therapeutic trials with the murine antibody BrE-3 and with the humanized anti-CEA antibody are already under way.
Immunoscintigraphy and Radioimmunotherapy
Published in Siegfried Matzku, Rolf A. Stahel, Antibodies in Diagnosis and Therapy, 2019
Radioimmunotherapy is a promising tool in treatment of various cancers, especially B-cell lymphomas and leukemias, but probably also as an adjuvant treatment modality in minimal residual disease of solid tumors. Continuing research should compare different radionuclides and antibodies in the same system (Bischof Delaloye et al., 1997) as well as the relative efficacy and toxicity of equivalent doses of RIT and external beam irradiation. It should be determined how heterogeneity of radiolabeled antibody deposition affects the absorbed dose distribution and relevant biological end points. Strategies for increasing and optimizing the therapeutic index of RIT have to be developed as well as combined treatment modalities (Knox, 1995).
Efficacy of nimotuzumab (hR3) conjugated with 131I or 90Y in laryngeal carcinoma xenograft mouse model
Published in International Journal of Radiation Biology, 2021
Thi-Thu Nguyen, Anh-Son Ho, Thi-Khanh-Giang Nguyen, Thi-Ngoc Nguyen, Van-Cuong Bui, Thanh-Binh Nguyen, Ho-Hong-Quang Dang, Dang-Khoa Nguyen, Thanh-Nhan Nguyen, Linh-Toan Nguyen
Radioimmunotherapy (RIT) using monoclonal antibodies labeled with radionuclides is a safe and effective cancer treatment that delivers cytotoxic radiation to target tumor cells. Monoclonal antibodies recognize and specifically bind to the surface of cancer cells. Many antibodies were administered for treatment of tumors, namely rituximab, ibritumomab tiuxetan, polatuzumab vedotin for hematological tumors or cetuximab, trastuzumab, bevacizumab, panitumumab, omburtamab, clivatuzumab for solid ones (Zaheer et al. 2019; Kaplon et al. 2020). Coupling of these antibodies with therapeutic radionuclides that emit ionizing radiation with short penetration depth into tissue, such as beta or alpha emitters (e.g. 131I, 90Y, 177Lu, 188Re, 67Cu, 225Ac, 211At, 213 Bi and 223Ra), can be used for specific deposit of considerable amounts of radiation energy in the tumor target. Therefore, RIT is a promising approach for the innovate treatment of cancer (Larson et al. 2015; Reulen et al. 2019).
Chemotherapy combinations for B-cell lymphoma and chemo-free approach in elderly patients: an update on best practice
Published in Expert Review of Hematology, 2020
Elisa Santambrogio, Mattia Novo, Delia Rota-Scalabrini, Umberto Vitolo
Aimed at avoiding chemotherapy, radioimmunotherapy has also been tested. 90Yttrium-Ibritumomab tiuxetan (zevalin®) is an anti-CD20 antibody conjugated with a radionuclide. It is typically used as consolidation therapy; however, it has been studied also in first-line treatment. A phase II trial treated 59 cases of FL with rituximab, as pretreatment followed by zevalin. After 3 months from radioimmunotherapy, MRD was evaluated; patients with MRD negativity were observed, while those still positive received consolidation with rituximab. Median age was 66 years with patients up to 83 years. ORR was 87%, with 56% CR or unconfirmed CR. With a median follow-up of 30.6 months, median OS was not reached and PFS was 25.9 months. The most common toxicities were transient thrombocytopenia and leukocytopenia and infections (20% grade 3, no infection of grade 4 observed) [74]. This trial demonstrated the good efficacy of zevalin, with a tolerable toxicity, even in elderly patients, particularly when more aggressive chemotherapies are not appropriated.
Development and clinical application of bispecific antibody in the treatment of colorectal cancer
Published in Expert Review of Clinical Immunology, 2020
Maryam Balibegloo, Nima Rezaei
Targeted radiotherapy with α or β emitting radionuclides is a promising strategy in cancer therapy. Due to CRC radioresistance, radioimmunotherapy is usually ineffective. Moreover, because of the toxicity, radiation dose would be limited. By means of PRIT, while the radiation dose to normal tissues is decreased, effective lethal doses are delivered to the cancer cells, via selective delivery. In this approach, the BsAb is administered intravenously, and after its accumulation in the tumor and clearance from the circulation, a radiolabeled hapten is administered, rapidly clearing from the circulation and captured in the tumor by BsAb owing an anti-hapten arm. Apart from the general principles of the strategy, PRIT protocols may vary by the BsAbs targeting different antigens, various radionuclides with distinctive properties such as half-life and emitted α or β particles, several haptens, and chelators. Many preclinical and clinical experiments have studied the safety and efficacy of BsAb applied in PRIT [118,126]. BsAbs may also perform diagnostic applications, such as imaging through being radiolabeled. AMG211 a CEA * CD3 recognizing BiTE was radiolabeled with zirconium-89 (89Zr) or fluorescent dye and administered to mice bearing xenografts including CRC model, to evaluate the tumor-targeting properties, bio-distribution, and generally the pharmacokinetics of AMG21 [172].