Radiolabeling of trastuzumab with 177Lu via DOTA, a new radiopharmaceutical for radioimmunotherapy of breast cancer

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

doi:10.1016/j.nucmedbio.2009.01.015

Cited by 59 publications

(75 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Trastuzumab radiolabeled with the b-emitters 90 Y, 177 Lu, and 188 Re, the Auger electron emitter 111 In, and a-particle emitters 212 Pb, 211 At, and 225 Ac has been evaluated in in vitro and in vivo therapy studies with encouraging results. [15][16][17][18][19][20][21][22][23][24] This concept is attractive because trastuzumab has known antitumor effects, which can be potentially additive or supraadditive when combined with the radiation dose delivered by RIT. In addition, immunogenicity of the antibody has been minimal in clinical trials, allowing for repeat administrations.…”

Section: Discussionmentioning

confidence: 99%

“…Trastuzumab radiolabeled with the b-emitters 90 Y, 177 Lu, and 188 Re, the Auger electron emitter 111 Indium ( 111 In), and aparticle emitters 212 Pb, 211 At, and 225 Ac has been evaluated in in vitro and in vivo therapy studies with encouraging results. [15][16][17][18][19][20][21][22][23][24] Radiometals may be more suited for this antibody compared with radioactive iodine, given the internalization of cell surface-bound antibody, which results in metabolism and dehalogenation. 25 Recent preclinical studies demonstrate the tumor targeting capabilities of 111 In-anti-HER2 and the therapeutic potential of 90 Y-labeled anti-HER2.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A Pretherapy Biodistribution and Dosimetry Study of Indium-111-Radiolabeled Trastuzumab in Patients with Human Epidermal Growth Factor Receptor 2-Overexpressing Breast Cancer

Wong

Raubitschek

Yamauchi

et al. 2010

Cancer Biotherapy and Radiopharmaceuticals

View full text Add to dashboard Cite

Purpose: The purposes of this study were to evaluate the organ biodistribution, pharmacokinetics, immunogenicity, and tumor uptake of 111 Indium ( 111 In)-MxDTPA-trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancers and to determine whether 90 Y-MxDTPAtrastuzumab should be evaluated in subsequent clinical therapy trials. Experimental Design: Patients with HER2-overexpressing breast cancers who were to undergo planned trastuzumab therapy first received unlabeled trastuzumab (4-8 mg/kg IV), followed 4 hours later by 5 mCi 111 InMxDTPA-trastuzumab (10 mg antibody). Serial blood samples, 24-hour urine collections, and nuclear scans were performed at defined time points for 7 days. Results: Eight (8) patients received 111 In-MxDTPA-trastuzumab, which was well tolerated with no adverse sideeffects. Three (3) of 7 patients with known lesions demonstrated positive imaging on nuclear scans. No antiantibody responses were observed for 2 months postinfusion. Organ doses (cGy/mCi) assuming radiolabeling with 90 Y were 19.9 for heart wall, 17.6 for liver, 4.6 for red marrow, and 2.8 for the whole body. Tumor doses ranged from 24 to 172 cGy/mCi. Conclusions: In summary, results from this study indicate that 90 Y-MxDTPA-trastuzumab is an appropriate agent to evaluate in therapy trials. No evidence of an immune response to 111 In-MxDTPA-trastuzumab was detected, predicting for the ability to administer multiple cycles. With the exception of cardiac uptake, pharmacokinetics and organ biodistribution were comparable to other 90 Y-labeled monoclonal antibodies previously evaluated in the clinic. Cardiac uptake was comparable to hepatic uptake and therefore predicted to not be prohibitively high as to result in dose-limiting cardiotoxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A Pretherapy Biodistribution and Dosimetry Study of Indium-111-Radiolabeled Trastuzumab in Patients with Human Epidermal Growth Factor Receptor 2-Overexpressing Breast Cancer

Wong

Raubitschek

Yamauchi

et al. 2010

Cancer Biotherapy and Radiopharmaceuticals

View full text Add to dashboard Cite

show abstract

“…The in vivo applications of key 177 Lu radiopharmaceuticals for a variety of therapeutic procedures include peptide receptor radionuclide therapy [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26], bone pain palliation [27][28][29][30][31][32][33], radiation synovectomy [34][35][36][37][38][39] and radioimmonutherapy [40][41][42][43][44][45][46]. There is a steadily expanding list of 177 Lu-labeled radiopharmaceuticals that is currently being evaluated at the preclinical research or at product development stages; these may potentially be used in vivo in humans for evaluation for radionuclide therapy [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Production of 177Lu for Targeted Radionuclide Therapy: Available Options

Dash

Pillai²,

Knapp

2015

Nucl Med Mol Imaging

243

166

View full text Add to dashboard Cite

Background: This review provides a comprehensive summary of the production of 177 Lu to meet expected future research and clinical demands. Availability of options represents the cornerstone for sustainable growth for the routine production of adequate activity levels of 177 Lu having the required quality for preparation of a variety of 177 Lu-labeled radiopharmaceuticals. The tremendous prospects associated with production of 177 Lu for use in targeted radionuclide therapy (TRT) dictate that a holistic consideration should evaluate all governing factors that determine its success. Methods: While both "direct" and "indirect" reactor production routes offer the possibility for sustainable 177 Lu availability, there are several issues and challenges that must be considered to realize the full potential of these production strategies. Results: This article presents a mini review on the latest developments, current status, key challenges and possibilities for the near future. Conclusion: A broad understanding and discussion of the issues associated with 177 Lu production and processing approaches would not only ensure sustained growth and future expansion for the availability and use of 177 Lu-labeled radiopharmaceuticals, but also help future developments.

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

Radiolabeling of trastuzumab with 177Lu via DOTA, a new radiopharmaceutical for radioimmunotherapy of breast cancer

Cited by 59 publications

References 17 publications

A Pretherapy Biodistribution and Dosimetry Study of Indium-111-Radiolabeled Trastuzumab in Patients with Human Epidermal Growth Factor Receptor 2-Overexpressing Breast Cancer

A Pretherapy Biodistribution and Dosimetry Study of Indium-111-Radiolabeled Trastuzumab in Patients with Human Epidermal Growth Factor Receptor 2-Overexpressing Breast Cancer

Production of 177Lu for Targeted Radionuclide Therapy: Available Options

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

Contact Info

Product

Resources

About