ImmunoPET: Antibody-Based PET Imaging in Solid Tumors

Manafi‐Farid, Reyhaneh; Ataeinia, Bahar; Ranjbar, Shaghayegh; Araghi, Zahra Jamshidi; Moradi, Mohammad; Pirich, Christian; Beheshti, Mohsen

doi:10.3389/fmed.2022.916693

Cited by 18 publications

(17 citation statements)

References 392 publications

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“…28 Given all of this, radiolabeled antibodies are being investigated for imaging and therapy [29][30][31] and, most recently, their use has also begun expanding to explicitly include theranostics. [32][33][34] Uses of antibodies for PET imaging and immunotherapy have primarily focused on oncology, and numerous antibody-based radiopharmaceuticals have been successfully developed for a broad spectrum of targets expressed by tumors, metastases, and/or malignant cells (for recent reviews, see Wei et al 35 and Manafi-Farid et al 36 ). There is also enormous interest in antibody-based radiopharmaceuticals in neuroscience and neuro-oncology applications.…”

Section: Introductionmentioning

confidence: 99%

“…Uses of antibodies for PET imaging and immunotherapy have primarily focused on oncology, and numerous antibody‐based radiopharmaceuticals have been successfully developed for a broad spectrum of targets expressed by tumors, metastases, and/or malignant cells (for recent reviews, see Wei et al 35 and Manafi‐Farid et al 36 ). There is also enormous interest in antibody‐based radiopharmaceuticals in neuroscience and neuro‐oncology applications 37 .…”

Section: Introductionmentioning

confidence: 99%

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Applications of radiolabeled antibodies in neuroscience and neuro‐oncology

Pakula

Scott

2023

Labelled Comp Radiopharmac

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Positron emission tomography (PET) is a powerful tool in medicine and drug development, allowing for non‐invasive imaging and quantitation of biological processes in live organisms. Targets are often probed with small molecules, but antibody‐based PET is expanding because of many benefits, including ease of design of new antibodies toward targets, as well as the very strong affinities that can be expected. Application of antibodies to PET imaging of targets in the central nervous system (CNS) is a particularly nascent field, but one with tremendous potential. In this review, we discuss the growth of PET in imaging of CNS targets, present the promises and progress in antibody‐based CNS PET, explore challenges faced by the field, and discuss questions that this promising approach will need to answer moving forward for imaging and perhaps even radiotherapy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Applications of radiolabeled antibodies in neuroscience and neuro‐oncology

Pakula

Scott

2023

Labelled Comp Radiopharmac

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“…Positron emission tomography (PET) is a highly sensitive and quantitative imaging modality that enables the noninvasive, real-time visualization of tumor biomarkers. Several tumor-targeted antibody PET agents have been developed and translated to date for applications in oncology. , ImmunoPET, a technology that combines the sensitivity of PET and the selectivity of antibodies, allows visualization of tumor biomarkers in vivo , and has the potential to be used as a complementary technique to IHC allowing for more accurate assessment of biomarkers in cancer diagnosis and treatment. , …”

Section: Introductionmentioning

confidence: 99%

“…Several tumortargeted antibody PET agents have been developed and translated to date for applications in oncology. 15,16 Immuno-PET, a technology that combines the sensitivity of PET and the selectivity of antibodies, allows visualization of tumor biomarkers in vivo, and has the potential to be used as a complementary technique to IHC allowing for more accurate assessment of biomarkers in cancer diagnosis and treatment. 17,18 Building on our previous work where we optimized the IHC detection of tumoral CAV1 using a murine CAV1-specific monoclonal antibody, 7 here we evaluated the utility of CAV1targeted immunoPET to detect tumoral CAV1 in HER2- expressing gastric tumors.…”

Section: ■ Introductionmentioning

confidence: 99%

PET and Optical Imaging of Caveolin-1 in Gastric Tumors

Surendra Panikar,

Shmuel,

Lewis

et al. 2023

ACS Omega

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Previous studies have suggested tumoral caveolin-1 (CAV1) as a predictive biomarker for the response to anti-HER2 antibody drug therapies in gastric tumors. In this study, radiolabeled and fluorescently labeled anti-CAV1 antibodies were developed and tested as an immunoPET or optical imaging agent to detect CAV1 in HER2-positive/CAV1-high NCIN87 gastric tumors. The expression of CAV1 receptors in NCIN87 gastric tumors and nontumor murine organs was determined by Western blot. Binding assays were performed to validate the anti-CAV1 antibody specificity for CAV1-expressing NCIN87 cancer cells. Subcutaneous and orthotopic NCIN87 xenografts were used for PET imaging and ex vivo biodistribution of the radioimmunoconjugate. Additional HER2-PET and CAV1-optical imaging was also performed to determine CAV1 in the HER2-positive tumors. 89 Zr-labeled anti-CAV1 antibody was able to bind to CAV1-expressing NCIN87 cells with a B max value of 2.7 × 10 3 CAV1 receptors/cell in vitro. ImmunoPET images demonstrated the localization of the antibody in subcutaneous NCIN87 xenografts. In the orthotopic model, CAV1 expression was also observed by optical imaging in the HER2-positive tumors previously imaged with HER2-PET. Ex vivo biodistribution analysis further confirmed these imaging results. The preclinical data from this study demonstrate the potential of using CAV1-PET and optical imaging for detecting gastric tumors.

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“…Additionally, the neonatal Fc receptor mediates a recycling process that shuttles the mAbs back into the blood plasma. – This extended circulation of mAbs in the plasma, in combination with the short physical half-life of preferred and typically used PET radionuclides for clinical imaging, implies some challenges with regard to both signal-to-noise ratios (due to radioactivity background in the blood pool) and radiation exposure of healthy tissue. While in immune PET-studies, e.g., for imaging of oncological diseases, , typically PET nuclides such as Zr-89 (78.4 h) and Ce-134 (75.8 h) for antibodies or Cu-64 (12.7 h) and Y-86 (14.7 h) for antibody fragments with moderate to high kinetics are commonly used, the radionuclide F-18 (110 min) in [ 18 F]aluminum fluoride radiochemistry is also reported . However, an immuno-PET approach with 18 F seems unusable due to the short physical half-life of the radionuclide and the long pharmacokinetic half-life of the mAbs .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Tetrazine Tracers for Pretargeted Imaging within the Central Nervous System

Edelmann,

Bredack,

Belli

et al. 2023

Bioconjugate Chem.

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The pretargeting approach separates the biological half-life of an antibody from the physical half-life of the radioisotope label, providing a strategy for reducing the radiation burden. A widely explored pretargeting approach makes use of the bioorthogonal click reaction between tetrazines (Tzs) and trans-cyclooctenes (TCOs), combining the targeting specificity of monoclonal antibodies (mAbs) with the rapid clearance and precise reaction of Tzs and TCOs. Such a strategy can allow for the targeting and imaging (e.g., by positron emission tomography (PET)) of molecular markers, which cannot be addressed by solely relying on small molecules. Tz derivatives that undergo inverse electron-demand Diels−Alder (IEDDA) reactions with an antibody bearing TCO moieties have been investigated. This study describes the synthesis and characterization of 11 cold Tz imaging agent candidates. These molecules have the potential to be radiolabeled with 18 F or 3 H, and with the former label, they could be of use as imaging tracers for positron emission tomography studies. Selection was made using a multiparameter optimization score for the central nervous system (CNS) PET tracers. Novel tetrazines were tested for their pH-dependent chemical stability. Those which turned out to be stable in a pH range of 6.5−8 were further characterized in in vitro assays with regard to their passive permeability, microsomal stability, and P-glycoprotein transport. Furthermore, selected Tzs were examined for their systemic clearance and CNS penetration in a single-dose pharmacokinetic study in rats. Two tetrazines were successfully labeled with 18 F, one of which showed brain penetration in a biodistribution study in mice. Another Tz was successfully tritium-labeled and used to demonstrate a bioorthogonal click reaction on a TCO-modified antibody. As a result, we identified one Tz as a potential fluorine-18-labeled CNS-PET agent and a second as a 3 H-radioligand for an IEDDA-based reaction with a modified brain-penetrating antibody.

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ImmunoPET: Antibody-Based PET Imaging in Solid Tumors

Cited by 18 publications

References 392 publications

Applications of radiolabeled antibodies in neuroscience and neuro‐oncology

Applications of radiolabeled antibodies in neuroscience and neuro‐oncology

PET and Optical Imaging of Caveolin-1 in Gastric Tumors

Evaluation of Tetrazine Tracers for Pretargeted Imaging within the Central Nervous System

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