177Lu labeling of Herceptin and preclinical validation as a new radiopharmaceutical for radioimmunotherapy of breast cancer

Rasaneh, Samira; Rajabi, Hamid; Babaei, Mohammad; Daha, Fariba Johari

doi:10.1016/j.nucmedbio.2010.07.001

Cited by 40 publications

(39 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The level of radioactivity attributable to the heart, lung and liver (blood pool) does not appear to clear over 4 or 7 d in either of these two studies. Furthermore, the radioactivity in the tumor, where 177 Lu-DOTA-trastuzumab is targeting a breast cancer xenograft, appears to diminish with time, not persisting in the tumor [9]. As mentioned earlier, this may be a result of dissociation of the 177 Lu from the trastuzumab, the injection of a suboptimal preparation of the RIC, or a combination thereof.…”

Section: Resultsmentioning

confidence: 99%

“…Numerous pre-clinical and clinical studies have reported on the potential of targeting HER2 for imaging and therapeutic applications using trastuzumab labeled with medically relevant radionuclides [8,9,10,11,12,13,14,15,16,17,25,38,39,40,17,25,38]. Extensive studies conducted in this laboratory with trastuzumab radiolabeled with 111 In, 86 Y and 213 Bi have utilized the CHX-A″-DTPA chelate [8,25].…”

Section: Discussionmentioning

confidence: 99%

“…Trastuzumab has proven to be an effective vehicle for targeting HER2 positive tumors to deliver therapeutic doses of radiation [8,9,10,11,12,13,14,15,16,17]. To date, studies in this laboratory have focused on and have demonstrated the therapeutic potential of trastuzumab as a delivery vehicle for α-particle radiation (using 212 Pb and 213 Bi) for the treatment of disseminated intraperitoneal disease [8,11,12,13,14].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pre-Clinical Assessment of 177Lu-Labeled Trastuzumab Targeting HER2 for Treatment and Management of Cancer Patients with Disseminated Intraperitoneal Disease

et al. 2011

View full text Add to dashboard Cite

Studies from this laboratory have demonstrated the potential of targeting HER2 for therapeutic and imaging applications with medically relevant radionuclides. To expand the repertoire of trastuzumab as a radioimmunoconjugate (RIC) vector, use of 177Lu was investigated. The combination of a 6.7 d half-life, lower energy β−-emissions (500 keV max; 130 keV ave), and an imagable γ-emission make 177Lu an attractive candidate for radioimmunotherapy (RIT) regimens for treatment of larger tumor burdens not possible with α-particle radiation. Radiolabeling trastuzumab-CHX-A″-DTPA with 177Lu was efficient with a specific binding of 60.8 ± 6.8% with HER2 positive SKOV-3 cells. Direct quantitation of tumor targeting and normal tissue uptake was performed with athymic mice bearing subcutaneous and intraperitoneal LS-174T xenografts; a peak tumor %ID/g of 24.70 ± 10.29 (96 h) and 31.70 ± 16.20 (72 h), respectively, was obtained. Normal tissue uptake of the RIC was minimal. Tumor targeting was also demonstrated by γ-scintigraphy. A therapy study administeringescalating doses of 177Lu-trastuzumab to mice bearing three day LS-174T i.p. xenografts established the effective therapeutic dose of i.p. administered 177Lu-trastuzumab at 375 μCi with a median survival of 124.5 d while a median survival of 10 d was noted for the control (untreated) group. In conclusion, trastuzumab radiolabeled with 177Lu has potential for treatment of disseminated, HER2 positive, peritoneal disease.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pre-Clinical Assessment of 177Lu-Labeled Trastuzumab Targeting HER2 for Treatment and Management of Cancer Patients with Disseminated Intraperitoneal Disease

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Radioimmunotherapy (RIT) has been investigated predominantly and extensively with trastuzumab and therapeutic radionuclides, such as b-emitters 177 Lu (57)(58)(59)(60), 90 Y (60,61), and 188 Re (62,63); Auger electron emitter 111 In (64); and even a-emitter actinium (12). All showed therapeutic efficacy in HER2-expressing xenografts.…”

Section: Her2-targeted Therapy With Radioactive Anti-her2 Probesmentioning

confidence: 99%

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

“…Для изучения воз-можностей проведения РИТ у данной категории пациентов был идентифицирован ряд мишеней, таких как РЭА, TAG-72, муцин-1 и L6 [16,17,37]. Муцин-1 представляет собой мембранный белок, гиперэкспрессия которого отмечается на поверх-ности 80 % опухолевых клеток, преимущественно при раке молочной железы и раке яичников [41].…”

unclassified

Radioimmunotherapy in the Treatment of Malignancies

Chernov¹,

Bragina²,

Синилкин³

et al. 2016

Sib. onkol. ž.

View full text Add to dashboard Cite

177Lu labeling of Herceptin and preclinical validation as a new radiopharmaceutical for radioimmunotherapy of breast cancer

Cited by 40 publications

References 21 publications

Pre-Clinical Assessment of 177Lu-Labeled Trastuzumab Targeting HER2 for Treatment and Management of Cancer Patients with Disseminated Intraperitoneal Disease

Pre-Clinical Assessment of 177Lu-Labeled Trastuzumab Targeting HER2 for Treatment and Management of Cancer Patients with Disseminated Intraperitoneal Disease

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

Radioimmunotherapy in the Treatment of Malignancies

Contact Info

Product

Resources

About