Preclinical optimization of antibody‐based radiopharmaceuticals for cancer imaging and radionuclide therapy—Model, vector, and radionuclide selection

Carter, Lukas M.; Poty, Sophie; Sharma, Sai Kiran; Lewis, Jason S.

doi:10.1002/jlcr.3612

Cited by 30 publications

(22 citation statements)

References 140 publications

(253 reference statements)

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“…Though antibodies possess features that favor them to achieve high tumor uptake, their large size hampers an access to tumor cells and their tumor penetration capabilities [82]. To overcome this problem, smaller PSMA antibody fragments have been developed, including minibodies, diabodies, single-chain variable region fragments, nanobodies, and monobodies ( Figure 2).…”

Section: Minibodies Diabodies Single-chain Variable Region Fragmentmentioning

confidence: 99%

Targeted Radionuclide Therapy of Prostate Cancer—From Basic Research to Clinical Perspectives

et al. 2020

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Prostate cancer is the most commonly diagnosed malignancy in men and the second leading cause of cancer-related deaths in Western civilization. Although localized prostate cancer can be treated effectively in different ways, almost all patients progress to the incurable metastatic castration-resistant prostate cancer. Due to the significant mortality and morbidity rate associated with the progression of this disease, there is an urgent need for new and targeted treatments. In this review, we summarize the recent advances in research on identification of prostate tissue-specific antigens for targeted therapy, generation of highly specific and selective molecules targeting these antigens, availability of therapeutic radionuclides for widespread medical applications, and recent achievements in the development of new-generation small-molecule inhibitors and antibody-based strategies for targeted prostate cancer therapy with alpha-, beta-, and Auger electron-emitting radionuclides.

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Section: Minibodies Diabodies Single-chain Variable Region Fragmentmentioning

confidence: 99%

Targeted Radionuclide Therapy of Prostate Cancer—From Basic Research to Clinical Perspectives

et al. 2020

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“…According to the "magic bullet" ("Zauberkugel") approach proposed by Paul Ehrlich (1900), the cytotoxic payload is delivered selectively to the malignant cells [22]. The vectors can be represented by small molecules, peptides, antibodies, or antibody derivatives, as well as by nanocarriers (as a full review of these would be exceeding the limits of this article, please refer, for instance, to [23][24][25][26][27][28]). [ 223 Ra]RaCl 2 , however, represents an exception due to its intrinsic bone-targeting properties, mimicking the chemical behavior and metabolic pathway of calcium, as both elements belong to the alkali earth metals.…”

Section: Introductionmentioning

confidence: 99%

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

2020

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Atomic in vivo nanogenerators such as actinium-225, thorium-227, and radium-223 are of increasing interest and importance in the treatment of patients with metastatic cancer diseases. This is due to their peculiar physical, chemical, and biological characteristics, leading to astonishing responses in otherwise resistant patients. Nevertheless, there are still a few obstacles and hurdles to be overcome that hamper the broader utilization in the clinical setting. Next to the limited supply and relatively high costs, the in vivo complex stability and the fate of the recoiling daughter radionuclides are substantial problems that need to be solved. In radiobiology, the mechanisms underlying treatment efficiency, possible resistance mechanisms, and late side effect occurrence are still far from being understood and need to be unraveled. In this review, the current knowledge on the scientific and clinical background of targeted alpha therapies is summarized. Furthermore, open issues and novel approaches with a focus on the future perspective are discussed. Once these are unraveled, targeted alpha therapies with atomic in vivo nanogenerators can be tailored to suit the needs of each patient when applying careful risk stratification and combination therapies. They have the potential to become one of the major treatment pillars in modern cancer management.

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“…The most critical item to consider when choosing a radionuclide is matching the physical half-life of the radionuclide with the biological half-life of the biomolecules to provide synchronous activity. This is essential to ensure that there is sufficient time for the RIC to accumulate in the tumor site before the radionuclide decay, to allow for good tumor visualization, and that the radiation exposure to normal tissues is as low as possible [17]. Biomolecules used for nuclear immuno-imaging and therapy have different formats that define and impact on their pharmacokinetics and development (Table 3).…”

Section: Radionuclide and Antibody-based Tumor Targeting Molecules For Radioimmunoimaging And Therapymentioning

confidence: 99%

“…Summary of the key properties of intact antibodies, antibody fragments, nanobodies, and affibodies[10,17].…”

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confidence: 99%

Enzymatic Methods for the Site-Specific Radiolabeling of Targeting Proteins

Bolzati

Spolaore

2021

Molecules

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Site-specific conjugation of proteins is currently required to produce homogenous derivatives for medicine applications. Proteins derivatized at specific positions of the polypeptide chain can actually show higher stability, superior pharmacokinetics, and activity in vivo, as compared with conjugates modified at heterogeneous sites. Moreover, they can be better characterized regarding the composition of the derivatization sites as well as the conformational and activity properties. To this aim, several site-specific derivatization approaches have been developed. Among these, enzymes are powerful tools that efficiently allow the generation of homogenous protein–drug conjugates under physiological conditions, thus preserving their native structure and activity. This review will summarize the progress made over the last decade on the use of enzymatic-based methodologies for the production of site-specific labeled immunoconjugates of interest for nuclear medicine. Enzymes used in this field, including microbial transglutaminase, sortase, galactosyltransferase, and lipoic acid ligase, will be overviewed and their recent applications in the radiopharmaceutical field will be described. Since nuclear medicine can benefit greatly from the production of homogenous derivatives, we hope that this review will aid the use of enzymes for the development of better radio-conjugates for diagnostic and therapeutic purposes.

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Preclinical optimization of antibody‐based radiopharmaceuticals for cancer imaging and radionuclide therapy—Model, vector, and radionuclide selection

Cited by 30 publications

References 140 publications

Targeted Radionuclide Therapy of Prostate Cancer—From Basic Research to Clinical Perspectives

Targeted Radionuclide Therapy of Prostate Cancer—From Basic Research to Clinical Perspectives

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

Enzymatic Methods for the Site-Specific Radiolabeling of Targeting Proteins

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