Bifunctional Chelators for Radiorhenium: Past, Present and Future Outlook

2022 ◽  
Author(s):  
Diana Melis ◽  
Andrew Burgoyne ◽  
Maarten Ooms ◽  
Gilles Gasser
Keyword(s):  
Nuclear Medicine ◽  
Cancer Treatment ◽  
Radionuclide Therapy ◽  
Targeted Radionuclide Therapy ◽  
Future Outlook ◽  
Bifunctional Chelators ◽  
Normal Tissues

Targeted radionuclide therapy (TRNT) is an ever-expanding field of nuclear medicine that provides a personalised approach to cancer treatment while limiting toxicity to normal tissues. It involves the radiolabelling of...

scholarly journals Bismuth-213 for Targeted Radionuclide Therapy: From Atom to Bedside

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 599
Author(s):  
Stephen Ahenkorah ◽  
Irwin Cassells ◽  
Christophe M. Deroose ◽  
Thomas Cardinaels ◽  
Andrew R. Burgoyne ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Radionuclide Therapy ◽  
Chemical Properties ◽  
High Energy ◽  
Magic Bullet ◽  
Targeted Radionuclide Therapy ◽  
Energy Photon ◽  
Normal Tissues ◽  
Preclinical And Clinical Studies ◽  
Alpha Therapy

In contrast to external high energy photon or proton therapy, targeted radionuclide therapy (TRNT) is a systemic cancer treatment allowing targeted irradiation of a primary tumor and all its metastases, resulting in less collateral damage to normal tissues. The α-emitting radionuclide bismuth-213 (213Bi) has interesting properties and can be considered as a magic bullet for TRNT. The benefits and drawbacks of targeted alpha therapy with 213Bi are discussed in this review, covering the entire chain from radionuclide production to bedside. First, the radionuclide properties and production of 225Ac and its daughter 213Bi are discussed, followed by the fundamental chemical properties of bismuth. Next, an overview of available acyclic and macrocyclic bifunctional chelators for bismuth and general considerations for designing a 213Bi-radiopharmaceutical are provided. Finally, we provide an overview of preclinical and clinical studies involving 213Bi-radiopharmaceuticals, as well as the future perspectives of this promising cancer treatment option.

scholarly journals Clinical trials in molecular radiotherapy—Tribulations and Triumphs Report of the NCRI CTRad meeting held at the Lift Islington, 8 June 2018

2019 ◽  
Vol 92 (1100) ◽  
pp. 20190117 ◽  
Author(s):  
Nadia Falzone ◽  
Rebecca Gregory ◽  
Matthew Aldridge ◽  
Samantha YA Terry ◽  
Glenn Flux
Keyword(s):  
Clinical Trials ◽  
Nuclear Medicine ◽  
Radionuclide Therapy ◽  
Targeted Radionuclide Therapy ◽  
Molecular Radiotherapy ◽  
Challenges And Opportunities ◽  
The Uk

It has been almost a decade since the commentary Molecular radiotherapy — the radionuclide raffle? by Gaze and Flux (2010). The overarching feeling then was that no individual or organisation has taken up the challenge, nationally or internationally, of championing molecular targeted radionuclide therapy in all its aspects. Here, we report on the recent NCRI–CTRad (Clinical Trials in Molecular Radiotherapy–Tribulations and Triumphs) meeting, held in London on the 8 June 2018. The meeting was organized by the NCRI–CTRad to review the challenges and opportunities for clinical trials in molecular radiotherapy, particularly focussing on investigator-led trials that incorporate imaging and dosimetry, and to discuss how the community can move forward. This meeting was organised in conjunction with the British Nuclear Medicine Society and reflects the progress of Nuclear Medicine in the UK.

scholarly journals Novel Bifunctional [16]aneS4-Derived Chelators for Soft Radiometals

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4603
Author(s):  
Natan J. W. Straathof ◽  
Charlotte B. Magnus ◽  
Fedor Zhuravlev ◽  
Andreas I. Jensen
Keyword(s):  
Carboxylic Acid ◽  
Metal Ions ◽  
Lewis Acid ◽  
Radionuclide Therapy ◽  
Targeted Radionuclide Therapy ◽  
Bifunctional Chelators ◽  
Soft Metal ◽  
Radiopharmaceutical Chemistry ◽  
Selection Of ◽  
General Method

The field of targeted radionuclide therapy is rapidly growing, highlighting the need for wider radionuclide availability. Soft Lewis acid ions, such as radioisotopes of platinum, rhodium and palladium, are particularly underdeveloped. This is due in part to a lack of compatible bifunctional chelators. These allow for the practical bioconjugation to targeting vectors, in turn enabling radiolabeling. The [16]andS4 macrocycle has been reported to chelate a number of relevant soft metal ions. In this work, we present a procedure for synthesizing [16]andS4 in 45% yield (five steps, 12% overall yield), together with a selection of strategies for preparing bifunctional derivatives. An ester-linked N-hydroxysuccimide ester (NHS, seven steps, 4% overall yield), an ether-linked isothiocyanate (NCS, eight steps, 5% overall yield) and an azide derivative were prepared. In addition, a new route to a carbon-carbon linked carboxylic acid functionalized derivative is presented. Finally, a general method for conjugating the NHS and NCS derivatives to a polar peptide (octreotide) is presented, by dissolution in water:acetonitrile (1:1), buffered to pH 9.4 using borate. The reported compounds will be readily applicable in radiopharmaceutical chemistry, by facilitating the labeling of a range of molecules, including peptides, with relevant soft radiometal ions.

scholarly journals The Application of Nuclear Medicine

2016 ◽  
Vol 1 (2) ◽  
pp. 81
Author(s):  
Giner Maslebu ◽  
Suryasatriya Trihandaru
Keyword(s):  
Nuclear Medicine ◽  
Neutron Capture ◽  
Radionuclide Therapy ◽  
Hybrid Imaging ◽  
Cross Validation ◽  
Neutron Capture Therapy ◽  
Targeted Radionuclide Therapy ◽  
Diagnostic Modality ◽  
Definition Of ◽  
Radiopharmaceutical Therapy

Currently, the practice of nuclear medicine in modern countries comprises a large number of procedures. It is applied to study function of organs/body systems, to visualize, to characterize, and to quantify the functional state of lesions and for targeted radionuclide therapy. This overview presents all kinds of application in nuclear medicine services. Instrumentation and radioactive/radiolabeled substances are the basic components for application. Biotechnology contributes to the development and production of biomolecules used in radiopharmaceuticals. As a diagnostic modality, imaging depicts radioactivity distribution as a function of time. Hybrid imaging provides more precise localization and definition of le-sions as well as molecular imaging cross validation. Counting tests study invivo<br />organ functions externally or assess analytes in the biologic samples. Radiopharmaceutical therapy can be applied directly into the lesion or targeted systemically. Nanotechnology facilitates targeting and opens the development of bimodal techniques. In addition, neutron application contributes to the advancement of nuclear medicine services, such as neutron activation analysis, neutron teletherapy and neutron capture therapy.

scholarly journals Bismuth-213 for Targeted Radionuclide Therapy: From Atom to Bedside

2021 ◽  
Author(s):  
Stephen Ahenkorah ◽  
Irwin Cassells ◽  
Christophe M Deroose ◽  
Thomas Cardinaels ◽  
Andrew R Burgoyne ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Vascular System ◽  
Chemical Properties ◽  
Proton Beam Therapy ◽  
High Energy ◽  
The Body ◽  
Magic Bullet ◽  
Targeted Radionuclide Therapy ◽  
Normal Tissues ◽  
Systemic Spread

Besides external high-energy photon or proton beam therapy, targeted radionuclide therapy (TRNT) is an alternative approach to deliver radiation to cancer cells. TRNT is distributed within the body by the vascular system and allows targeted irradiation of a primary tumor and all its metastases, resulting in substantially less collateral damage to normal tissues as compared to ex-ternal beam radiotherapy (EBRT). It is a systemic cancer therapy, tackling systemic spread of the disease, which is the cause of death in most cancer patients. The &alpha;-emitting radionuclide bis-muth-213 (213Bi) has interesting properties and can be considered as a magic bullet for TRNT. The benefits and drawbacks of targeted alpha therapy with 213Bi are discussed in this review, covering the entire chain from radionuclide production to bedside. First, the radionuclide properties and production of 225Ac and its daughter 213Bi are discussed, followed by the fundamental chemical properties of bismuth. Next, an overview of available acyclic and macrocyclic bifunctional chelators for bismuth, and general considerations for designing a 213Bi-radiopharmaceutical are provided. Finally, we will provide an overview of preclinical and clinical studies involving 213Bi-radiopharmaceuticals, as well as the future perspectives of this promising cancer treatment option.

NOB1: A Potential Biomarker or Target in Cancer

2019 ◽  
Vol 20 (10) ◽  
pp. 1081-1089
Author(s):  
Weiwei Ke ◽  
Zaiming Lu ◽  
Xiangxuan Zhao
Keyword(s):  
Cancer Treatment ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Binding Protein ◽  
Tumor Development ◽  
Anticancer Therapy ◽  
Research Progress ◽  
Normal Tissues ◽  
Potential Biomarker

Human NIN1/RPN12 binding protein 1 homolog (NOB1), an RNA binding protein, is expressed ubiquitously in normal tissues such as the lung, liver, and spleen. Its core physiological function is to regulate protease activities and participate in maintaining RNA metabolism and stability. NOB1 is overexpressed in a variety of cancers, including pancreatic cancer, non-small cell lung cancer, ovarian cancer, prostate carcinoma, osteosarcoma, papillary thyroid carcinoma, colorectal cancer, and glioma. Although existing data indicate that NOB1 overexpression is associated with cancer growth, invasion, and poor prognosis, the molecular mechanisms behind these effects and its exact roles remain unclear. Several studies have confirmed that NOB1 is clinically relevant in different cancers, and further research at the molecular level will help evaluate the role of NOB1 in tumors. NOB1 has become an attractive target in anticancer therapy because it is overexpressed in many cancers and mediates different stages of tumor development. Elucidating the role of NOB1 in different signaling pathways as a potential cancer treatment will provide new ideas for existing cancer treatment methods. This review summarizes the research progress made into NOB1 in cancer in the past decade; this information provides valuable clues and theoretical guidance for future anticancer therapy by targeting NOB1.

Resveratrol as an Adjuvant for Normal Tissues Protection and Tumor Sensitization

2020 ◽  
Vol 20 (2) ◽  
pp. 130-145 ◽  
Author(s):  
Keywan Mortezaee ◽  
Masoud Najafi ◽  
Bagher Farhood ◽  
Amirhossein Ahmadi ◽  
Dheyauldeen Shabeeb ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Clinical Studies ◽  
Normal Tissue ◽  
Medical Science ◽  
Treatment Modalities ◽  
Radiation Toxicity ◽  
Normal Tissues ◽  
Normal Tissue Toxicity

Cancer is one of the most complicated diseases in present-day medical science. Yearly, several studies suggest various strategies for preventing carcinogenesis. Furthermore, experiments for the treatment of cancer with low side effects are ongoing. Chemotherapy, targeted therapy, radiotherapy and immunotherapy are the most common non-invasive strategies for cancer treatment. One of the most challenging issues encountered with these modalities is low effectiveness, as well as normal tissue toxicity for chemo-radiation therapy. The use of some agents as adjuvants has been suggested to improve tumor responses and also alleviate normal tissue toxicity. Resveratrol, a natural flavonoid, has attracted a lot of attention for the management of both tumor and normal tissue responses to various modalities of cancer therapy. As an antioxidant and anti-inflammatory agent, in vitro and in vivo studies show that it is able to mitigate chemo-radiation toxicity in normal tissues. However, clinical studies to confirm the usage of resveratrol as a chemo-radioprotector are lacking. In addition, it can sensitize various types of cancer cells to both chemotherapy drugs and radiation. In recent years, some clinical studies suggested that resveratrol may have an effect on inducing cancer cell killing. Yet, clinical translation of resveratrol has not yielded desirable results for the combination of resveratrol with radiotherapy, targeted therapy or immunotherapy. In this paper, we review the potential role of resveratrol for preserving normal tissues and sensitization of cancer cells in combination with different cancer treatment modalities.

Organs dosimetry in targeted radionuclide therapy

2021 ◽  
pp. 109668
Author(s):  
Meshari Alnaaimi ◽  
Abdelmoneim Sulieman ◽  
Mohammed Alkhorayef ◽  
Hasan Salah ◽  
Musa Alduaij ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Targeted Radionuclide Therapy
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