Monoclonal antibody based radiopharmaceuticals for imaging and therapy

Lin, Min; Paolillo, Vincenzo; Le, Dao; Macapinlac, Homer A.; Ravizzini, Gregory

doi:10.1016/j.currproblcancer.2021.100796

Cited by 20 publications

(21 citation statements)

References 72 publications

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“…24 When compared with rituximab (uptake of 28.6% ID/g) and tositumomab, 89 Zr-labeled ofatumumab and obinutuzumab demonstrated better tumor uptake in human lymphoma xenografts (42.4% and 32.6% ID/g respectively), 24 thus showing potential for RIT. 8 Human CDH3 (P-Cadherin) as a Target…”

Section: Cd20 As a Targetmentioning

confidence: 99%

“…Both were radiolabeled with 89 Zr to evaluate tumor targeting efficacy by PET/CT imaging in a preclinical mouse model with xenografts that overexpress CD20 24 . When compared with rituximab (uptake of 28.6% ID/g) and tositumomab, 89 Zr-labeled ofatumumab and obinutuzumab demonstrated better tumor uptake in human lymphoma xenografts (42.4% and 32.6% ID/g respectively), 24 thus showing potential for RIT 8 …”

Section: Cd20 As a Targetmentioning

confidence: 99%

“…On the other hand, it has been shown that antibody fragments with faster PK or clearance rates can be labeled with shorter half-life radionuclides, for example, 18 F, 64 Cu, and 68 Ga, for effective imaging applications (Table 1). 8 For targeted therapy, the diagnostic radionuclide component of the labeled mAb can be replaced with an appropriate therapeutic radionuclide emitting β − radiation (β − ), α-particles (α), or Auger electrons with the intent to deliver a sufficiently large radiation dose to the tumor. 9 β − Emitters with energies between 30 keVand 2.3 MeV have a low LET (linear energy transfer), approximately 0.2 keV/μm, and a relatively broad penetrating range in tissue (0.5-12 mm).…”

mentioning

confidence: 99%

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confidence: 99%

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The Role of Radiolabeled Monoclonal Antibodies in Cancer Imaging and ADC Treatment

Martiniova¹,

Zieliński²,

Lin³

et al. 2022

Cancer J

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Antibody-drug conjugates (ADCs) are designed to deliver cytotoxic payloads to distinctive target-expressing cancer cells. Following internalization, the ADCs are routed to different compartments in the cells, where cleavage of the linker causes release of the cytotoxic cargo. With such a delivery system, more effective payloads can reach cancer cells, allowing for more efficient treatment and dosing schedule. The monoclonal antibody (mAb) component of ADC plays a crucial role in the effective targeting of cancer cell-specific antigens while minimizing binding to normal cells. Often, the same mAbs used in ADCs can be labeled instead with radionuclides suitable for positron emission tomography or gamma-camera scintigraphy. To achieve high sensitivity and specificity for imaging, radiolabeled mAbs must have high affinity for the antigen, favorable pharmacokinetic properties, and a low toxicity profile. The use of radiolabeled mAbs permits the noninvasive interrogation of specific target expression on tumor cells and assessment of tumor heterogeneity in vivo by a simple diagnostic imaging scan that may include the whole body in the field of view. With this approach, radiolabeled mAbs can serve as important imaging biomarkers to predict the optimal delivery of ADCs to tumors and be used to monitor therapy with follow-up scans. Moreover, the same mAb can then be radiolabeled with an analogous radionuclide for the delivery of β-emitters, α-particles, or Auger electrons as part of a radioimmunotherapy approach. The purpose of this review is to introduce key concepts regarding radiolabeled mAbs targeting various tumor antigens (CD20, CDH3, type I insulinlike growth factor receptor, prostate-specific membrane antigen, and human epidermal growth factor receptor 2) that are being used in the clinical setting or undergoing development.

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Section: Cd20 As a Targetmentioning

confidence: 99%

Section: Cd20 As a Targetmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The Role of Radiolabeled Monoclonal Antibodies in Cancer Imaging and ADC Treatment

Martiniova¹,

Zieliński²,

Lin³

et al. 2022

Cancer J

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“…Finally, the pharmacokinetic properties of the antibody or antibody fragment in relation to the imaging timepoints are also a key consideration when designing imaging experiments using such species. The PET imaging (and treatment) of a variety of cancers and other disorders in the periphery using highly selective and specific monoclonal antibodies and antibody fragments has revolutionised our understanding of these conditions over the last 10 years 2,25–30 . Studies in this area have highlighted the fact that these large molecules tend to be slow to accumulate at their target site and are also slow to clear from the circulation.…”

Section: Introductionmentioning

confidence: 99%

The inverse electron demand Diels–Alder cycloaddition with carbon‐11 and fluorine‐18: A gateway to pretargeted imaging across the blood–brain barrier

Zientek

Thompson

Sephton

et al. 2023

Labelled Comp Radiopharmac

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Monoclonal Antibody and Targeted Toxin Therapy

Bast¹,

Zalutsky²

2022

Holland‐Frei Cancer Medicine

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Overview Monoclonal antibodies have impacted significantly on the care of patients with cancer. Overall, the US FDA has approved 100 different monoclonal antibodies for the treatment of human diseases. More than 40 monoclonal antibodies, cytotoxic drug conjugates, radionuclide conjugates, and targeted toxins have been approved for the treatment of more than two dozen different malignancies. Useful monoclonal antibodies have most frequently targeted structural proteins and receptors on the cancer cell surface (CD20 by rituximab, HER2 by trastuzumab, and pertuzumab), inhibiting growth, inducing apoptosis, and enhancing chemotherapy, but some have targeted cytokines (IL‐6 by siltuximab), growth factors (vascular endothelial growth factor (VEGF) by bevacizumab), and growth factor receptors (VEGFR2 by ramucirumab) that affect both cancer cells and normal stromal cells including endothelial cells and lymphocytes. Monoclonal antibodies have disrupted checkpoint inhibition of effector T lymphocytes by blocking CTLA4 (ipilimumab), PD1 (pembrolizumab, nivolumab, and cemiplimab), and PD‐L1 (atezolizumab, durvalumab, and avelumab). In the case of trastuzumab and pertuzumab, binding of the two antibodies to different sites on the HER2 cell surface receptor has produced greater antitumor activity than either alone. Enhanced cancer cell killing has also been achieved by conjugation of antibodies with cytotoxic drugs (emtansine to anti‐HER2 trastuzumab and vedotin to anti‐CD30 brentuximab) or radionuclide conjugates ( 90 Y to anti‐CD20 ibritumomab tiuxetan) permitting effective treatment of patients who had failed therapy with unconjugated antibodies. There are several barriers to effective therapy with monoclonal antibodies including antigen specificity, antigenic modulation, heterogeneity of antigen expression, effective delivery of antibodies to cancer cells, potency of effector mechanisms, and response to immunologically foreign globulin. The latter problem has been circumvented with the use of chimeric constructs, humanization of murine antibodies, and developing genetically engineered mice with the ability to develop fully human antibodies. Use of unconjugated antibodies is likely to improve as our knowledge of tumor biology and immunology grows, identifying targets such as OX‐40 ligand. Use of smaller molecularly engineered binding constructs may improve pharmacokinetics and pharmacodynamics of monoclonal antibody and conjugate therapy. Combinations of antibodies may be required to compensate for antigenic heterogeneity. Development of more effective antibody–drug conjugates will require the identification of monoclonal reagents that target tumor‐initiating stem cells. Use of antibody fragments, pretargeting, and the use of alpha‐emitters are promising approaches to improving antibody–radionuclide conjugates. Development of targeted toxins must be further explored.

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Monoclonal antibody based radiopharmaceuticals for imaging and therapy

Cited by 20 publications

References 72 publications

The Role of Radiolabeled Monoclonal Antibodies in Cancer Imaging and ADC Treatment

The Role of Radiolabeled Monoclonal Antibodies in Cancer Imaging and ADC Treatment

The inverse electron demand Diels–Alder cycloaddition with carbon‐11 and fluorine‐18: A gateway to pretargeted imaging across the blood–brain barrier

Monoclonal Antibody and Targeted Toxin Therapy

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