A Single Treatment of Yttrium-90-labeled CHX-A″–C6.5 Diabody Inhibits the Growth of Established Human Tumor Xenografts in Immunodeficient Mice

Adams, Gregory P.; Shaller, Calvin; Dadachova, Ekaterina; Simmons, Heidi; Horak, Eva; Tesfaye, Abohawariat; Klein‐Szanto, Andres J.; Marks, James D.; Brechbiel, Martin W.; Weiner, Louis M.

doi:10.1158/0008-5472.can-03-2382

Cited by 78 publications

(48 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Affibody ABY-002 radiolabeled with 111 In for SPECT as well as with 68 Ga for PET was shown to specifically target HER2-expressing xenografts in vivo with both isotopes, but the pharmacokinetic profile for 68 Ga-radiolabeled ABY-002 was favored (20). Both tracers were investigated further in BC patients (22); the findings were in agreement with the preclinical data.…”

Section: Preclinical Settingsupporting

confidence: 72%

“…In contrast, its bioengineered derived fragments [Fab fragments, F(ab9) 2 ] and variants (scFv, diabodies, and minibodies) and nontraditional protein scaffolds (Affibody molecules, Nanobodies, and anticalins) result in faster pharmacokinetics with similar affinity and specificity (9). These low-molecular-weight probes can be radiolabeled with isotopes-such as 68 Ga, 18 F, 64 Cu, and 76 Br for PET imaging-that have a short halflife, allowing imaging on the day of injection with a low radiation burden. In contrast, when mAbs are radiolabeled with isotopes that have a longer half-life-such as 89 Zr, 124 I, and 86 Y for PET imaging and 111 In for SPECT imaging-images can be retrieved up to several days after tracer injection, allowing optimal uptake in tumor tissue.…”

Section: Imaging Of Her2 (Target) Expressionmentioning

confidence: 99%

“…Several anti-HER2 Affibody molecules have also been labeled with 68 Ga, 18 F, 64 Cu, and 11 C for PET and with 99m Tc and 111 In for SPECT (18)(19)(20)(21). Affibody ABY-002 radiolabeled with 111 In for SPECT as well as with 68 Ga for PET was shown to specifically target HER2-expressing xenografts in vivo with both isotopes, but the pharmacokinetic profile for 68 Ga-radiolabeled ABY-002 was favored (20).…”

Section: Preclinical Settingmentioning

confidence: 99%

See 2 more Smart Citations

Imaging Diagnostic and Therapeutic Targets: Human Epidermal Growth Factor Receptor 2

et al. 2016

View full text Add to dashboard Cite

Since the approval of trastuzumab, a humanized monoclonal antibody against the extracellular domain of human epidermal growth factor receptor 2 (HER2), 3 other HER2-targeting agents have gained regulatory approval: lapatinib, pertuzumab, and trastuzumab-emtansine. These agents have revolutionized the management of HER2-positive breast cancer, highlighting the concept that targeted therapies are successful when patients exhibit tumor-selective expression of a molecular target-in this case, HER2. However, response prediction and innate or acquired resistance remain serious concerns. Predictive biomarkers of a response-which could help in the selection of patients who might benefit from a selected targeted therapy-are currently lacking. Molecular imaging with anti-HER2 probes allows the noninvasive, whole-body assessment of HER2 tumor burden and has the potential to improve patient selection, optimize the dose and schedule, and rationalize assessment of the response to anti-HER2 therapies. Furthermore, unlike biopsy-based HER2 assessment, this approach can reveal inter-or intratumoral heterogeneity as well as variations in HER2 expression over time. This review summarizes the available literature and the current status of molecular imaging as a tool for the assessment of HER2 (target) expression or the prediction of an early treatment response in early and advanced HER2-positive breast cancer. Human epidermal growth factor receptor 2 (HER2) is overexpressed in several cancers, including breast, gastric, ovary, prostate, bladder, and lung cancers, and is a proven therapeutic target in the first 2 tumor types (1,2). In breast cancer (BC), in particular, HER2 overexpression is found in 15%-25% of patients and is associated with a clinically aggressive course. Successful targeting of HER2 with a range of anti-HER2 drugs has resulted in markedly improved patient outcomes in both advanced and early disease settings (3).However, the presence of a target (in this case, HER2) does not always guarantee benefit from matched targeted therapies because downstream signaling resistance or escape can occur. In HER2-overexpressing BC, it has been estimated that about 50% of patients with metastases do not benefit from anti-HER2 therapies (4), and not a single biomarker for identifying nonresponding patients has yet been validated (5).Furthermore, there is increasing evidence of temporal and spatial heterogeneity in BC HER2 overexpression. Patients with negative test results at diagnosis can have positive test results later in the disease course and vice versa, a fact that explains why biopsy of metastatic disease is a strong recommendation of many clinical treatment guidelines (6). Heterogeneity in biomarker expression at metastatic sites is only beginning to be recognized, with growing appreciation for molecular imaging.This article focuses on HER2-positive BC and provides a comprehensive overview of the present and future roles of molecular imaging in improving target mapping, predicting benefit from chemotherapy with or without ...

show abstract

Section: Preclinical Settingsupporting

confidence: 72%

Section: Imaging Of Her2 (Target) Expressionmentioning

confidence: 99%

Section: Preclinical Settingmentioning

confidence: 99%

See 1 more Smart Citation

Imaging Diagnostic and Therapeutic Targets: Human Epidermal Growth Factor Receptor 2

et al. 2016

View full text Add to dashboard Cite

show abstract

“…However, when a large portion of the radionuclide is filtered through the kidneys, it is important to carefully assess the potential for renal toxicity. Severe renal toxicity associated with directly radiolabeled FabV (31) and diabodies (32) has been reported in mice but there is a considerably higher retention of these agents in the kidneys than that seen with 90 Ybiotin or 90 Y-peptide. There has been an extensive examination of renal toxicity associated with the use of radiolabeled somatostatin receptor peptides in rats and humans (33,34), which suggested that renal toxicity requires several months to be detected.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Advantage of Pretargeted Radioimmunotherapy Using a Recombinant Bispecific Antibody in a Human Colon Cancer Xenograft

Karacay

Brard

Sharkey

et al. 2005

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Among the approaches taken are pretargeting methods (49), the use of genetically engineered immunoconstructs with molecular mass intermediate between that of intact immunoglobulin G and FabV fragments (50,51), and combination of radioimmunotherapy with other therapeutic modalities such as external beam irradiation or chemotherapy (52 -54). Chelated radiometals represent an alternate source of residualizing labels available for radioimmunotherapy, remaining trapped in lysosomes in the form of lysine adducts of the respective metal chelates (55).…”

Section: Discussionmentioning

confidence: 99%

Advantage of a Residualizing Iodine Radiolabel in the Therapy of a Colon Cancer Xenograft Targeted with an Anticarcinoembryonic Antigen Monoclonal Antibody

Stein

Govindan²,

Hayes³

et al. 2005

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: A disadvantage of conventionally radioiodinated monoclonal antibodies (mAb) for cancer therapy is the short retention time of the radionuclide within target cells. To address this issue, we recently developed a method in which radioiodine is introduced onto antibodies using an adduct consisting of a nonmetabolizable peptide attached to the aminopolycarboxylate diethylenetriaminepentaacetic acid, designated IMP-R4.This adduct causes the radioiodine to become trapped in lysosomes following antibody catabolism. Clinical-scale production of 131

show abstract

A Single Treatment of Yttrium-90-labeled CHX-A″–C6.5 Diabody Inhibits the Growth of Established Human Tumor Xenografts in Immunodeficient Mice

Abstract: ABSTRACT

Cited by 78 publications

References 25 publications

Imaging Diagnostic and Therapeutic Targets: Human Epidermal Growth Factor Receptor 2

Imaging Diagnostic and Therapeutic Targets: Human Epidermal Growth Factor Receptor 2

Therapeutic Advantage of Pretargeted Radioimmunotherapy Using a Recombinant Bispecific Antibody in a Human Colon Cancer Xenograft

Advantage of a Residualizing Iodine Radiolabel in the Therapy of a Colon Cancer Xenograft Targeted with an Anticarcinoembryonic Antigen Monoclonal Antibody

Contact Info

Product

Resources

About