Emerging Role of ImmunoPET in Receptor Targeted Cancer Therapy

Mařı́k, Jan; Junutula, Jagath R.

doi:10.2174/156720111793663589

Cited by 12 publications

(4 citation statements)

References 66 publications

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“…Nowhere is this more easily observed than with the advent of personalized medicine and the expansion of monoclonal antibodies (mAbs) as targeted therapeutics. PET performed with radiolabeled mAbs (immunoPET) as target specific tracers allows for the whole body assessment of biomarker expression and the non-invasive biodistribution of therapeutic antibodies 1 , 2 . Since monoclonal antibodies exhibit a much longer biological half-life than small molecules the most widely used positron emitting radionuclide 18 F (T 1/2 = 110 min) is not ideal for the radiolabeling of monoclonal antibodies.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a 3-hydroxypyridin-2-one (2,3-HOPO) Based Macrocyclic Chelator for ⁸⁹Zr⁴⁺ and Its Use for ImmunoPET Imaging of HER2 Positive Model of Ovarian Carcinoma in Mice

Tinianow¹,

Pandya

Pailloux

et al. 2016

Theranostics

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A novel octadentate 3-hydroxypyridin-2-one (2,3-HOPO) based di-macrocyclic ligand was evaluated for chelation of 89Zr; subsequently, it was used as a bi-functional chelator for preparation of 89Zr-labeled antibodies. Quantitative chelation of 89Zr4+ with the octadentate ligand forming 89ZrL complex was achieved under mild conditions within 15 minutes. The 89Zr-complex was stable in vitro in presence of DTPA, but a slow degradation was observed in serum. In vivo, the hydrophilic 89Zr-complex showed prevalently renal excretion; and an elevated bone uptake of radioactivity suggested a partial release of 89Zr4+ from the complex.The 2,3-HOPO based ligand was conjugated to the monoclonal antibodies, HER2-specific trastuzumab and an isotypic anti-gD antibody, using a p-phenylene bis-isothiocyanate linker to yield products with an average loading of less than 2 chelates per antibody. Conjugated antibodies were labeled with 89Zr under mild conditions providing the PET tracers in 60-69% yield. Despite the limited stability in mouse serum; the PET tracers performed very well in vivo. The PET imaging in mouse model of HER2 positive ovarian carcinoma showed tumor uptake of 89Zr-trastuzumab (29.2 ± 12.9 %ID/g) indistinguishable (p = 0.488) from the uptake of positive control 89Zr-DFO-trastuzumab (26.1 ± 3.3 %ID/g).In conclusion, the newly developed 3-hydroxypyridin-2-one based di-macrocyclic chelator provides a viable alternative to DFO-based heterobifunctional ligands for preparation of 89Zr-labeled monoclonal antibodies for immunoPET studies.

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Section: Introductionmentioning

confidence: 99%

Evaluation of a 3-hydroxypyridin-2-one (2,3-HOPO) Based Macrocyclic Chelator for ⁸⁹Zr⁴⁺ and Its Use for ImmunoPET Imaging of HER2 Positive Model of Ovarian Carcinoma in Mice

Tinianow¹,

Pandya

Pailloux

et al. 2016

Theranostics

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“…These pharmaceutical developments rely crucially on the antibody's ability to localize at sites of disease. Immuno-PET, a molecular imaging technique combining the high resolution and sensitivity of positron emission tomography (PET) and the selective localization of antibodies at their target in vivo, has profited from recent technical advances and the availability of Good Manufacturing Practice (GMP)-grade radionuclides, and might play an important role in the future both in cancer staging and tailoring of therapy (6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Radretumab Radioimmunotherapy in Patients with Brain Metastasis: A 124I-L19SIP Dosimetric PET Study

Poli

Bianchi

Virotta

et al. 2013

Cancer Immunology Research

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Radioimmunotherapy (RIT) with 131 I-labeled L19SIP (radretumab; a small immunoprotein format antibody directed against the ED-B domain of fibronectin; $80 kDa molecular weight) has been investigated in several clinical trials. Here, we describe the use of immuno-PET imaging with iodine-124 ( 124 I)-labeled L19SIP to predict doses delivered to tumor lesions and healthy organs by a subsequent radretumab RIT in patients with brain metastases from solid cancer. Bone marrow doses were evaluated both during the diagnostic phase and posttherapy, measuring activities in blood (germanium detector) and whole body (lanthanum bromide detector). Expected doses for radretumab administration (4,107 MBq/m 2 ) were calculated from data obtained after administration of an average of 167 MBq 124 I-L19SIP to 6 patients. To assess lesion average doses, the positron emission tomography (PET) scanner was calibrated for the use of 124 I with an International Electrotechnical Commission (IEC) Body Phantom and recovery coefficients were calculated. The average dose to bone red marrow was 0.21 Gy/GBq, with high correlation between provisional and actual posttherapy doses. Although the fraction of injected activity in normal organs was similar in different patients, the antibody uptake in the neoplastic lesions varied by as much as a factor of 60. Immuno-PET with 124 I-labeled L19SIP offers significant advantages over conventional 131 I imaging, in particular accuracy of dosimetric results. Furthermore, the study indicates that antibody uptake can be highly variable even in different lesions of the same patient and that immuno-PET procedures may guide product development with armed antibodies. Cancer Immunol Res; 1(2); 134-43. Ó2013 AACR.

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“… 107 In addition, peptides and other receptor-targeting compounds, such as nanobodies or bispecific antibodies, are being used to design novel immune-PET tracers. 107 , 108 By dynamically monitoring tumor antigens’ expression, immune-PET imaging is a promising technique for evaluating the efficacy of cancer-targeted therapy.…”

Section: Molecular Imagingmentioning

confidence: 99%

Molecular and functional imaging in cancer-targeted therapy: current applications and future directions

Bai

Qiu

Zhang

2023

Sig Transduct Target Ther

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Targeted anticancer drugs block cancer cell growth by interfering with specific signaling pathways vital to carcinogenesis and tumor growth rather than harming all rapidly dividing cells as in cytotoxic chemotherapy. The Response Evaluation Criteria in Solid Tumor (RECIST) system has been used to assess tumor response to therapy via changes in the size of target lesions as measured by calipers, conventional anatomically based imaging modalities such as computed tomography (CT), and magnetic resonance imaging (MRI), and other imaging methods. However, RECIST is sometimes inaccurate in assessing the efficacy of targeted therapy drugs because of the poor correlation between tumor size and treatment-induced tumor necrosis or shrinkage. This approach might also result in delayed identification of response when the therapy does confer a reduction in tumor size. Innovative molecular imaging techniques have rapidly gained importance in the dawning era of targeted therapy as they can visualize, characterize, and quantify biological processes at the cellular, subcellular, or even molecular level rather than at the anatomical level. This review summarizes different targeted cell signaling pathways, various molecular imaging techniques, and developed probes. Moreover, the application of molecular imaging for evaluating treatment response and related clinical outcome is also systematically outlined. In the future, more attention should be paid to promoting the clinical translation of molecular imaging in evaluating the sensitivity to targeted therapy with biocompatible probes. In particular, multimodal imaging technologies incorporating advanced artificial intelligence should be developed to comprehensively and accurately assess cancer-targeted therapy, in addition to RECIST-based methods.

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Emerging Role of ImmunoPET in Receptor Targeted Cancer Therapy

Cited by 12 publications

References 66 publications

Evaluation of a 3-hydroxypyridin-2-one (2,3-HOPO) Based Macrocyclic Chelator for ⁸⁹Zr⁴⁺ and Its Use for ImmunoPET Imaging of HER2 Positive Model of Ovarian Carcinoma in Mice

Evaluation of a 3-hydroxypyridin-2-one (2,3-HOPO) Based Macrocyclic Chelator for ⁸⁹Zr⁴⁺ and Its Use for ImmunoPET Imaging of HER2 Positive Model of Ovarian Carcinoma in Mice

Radretumab Radioimmunotherapy in Patients with Brain Metastasis: A 124I-L19SIP Dosimetric PET Study

Molecular and functional imaging in cancer-targeted therapy: current applications and future directions

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Emerging Role of ImmunoPET in Receptor Targeted Cancer Therapy

Cited by 12 publications

References 66 publications

Evaluation of a 3-hydroxypyridin-2-one (2,3-HOPO) Based Macrocyclic Chelator for 89Zr4+ and Its Use for ImmunoPET Imaging of HER2 Positive Model of Ovarian Carcinoma in Mice

Evaluation of a 3-hydroxypyridin-2-one (2,3-HOPO) Based Macrocyclic Chelator for 89Zr4+ and Its Use for ImmunoPET Imaging of HER2 Positive Model of Ovarian Carcinoma in Mice

Radretumab Radioimmunotherapy in Patients with Brain Metastasis: A 124I-L19SIP Dosimetric PET Study

Molecular and functional imaging in cancer-targeted therapy: current applications and future directions

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Evaluation of a 3-hydroxypyridin-2-one (2,3-HOPO) Based Macrocyclic Chelator for ⁸⁹Zr⁴⁺ and Its Use for ImmunoPET Imaging of HER2 Positive Model of Ovarian Carcinoma in Mice

Evaluation of a 3-hydroxypyridin-2-one (2,3-HOPO) Based Macrocyclic Chelator for ⁸⁹Zr⁴⁺ and Its Use for ImmunoPET Imaging of HER2 Positive Model of Ovarian Carcinoma in Mice