Indium-111–Labeled Trastuzumab Scintigraphy in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

Perik, Patrick J.; Hooge, Marjolijn N. Lub-de; Gietema, Jourik A.; Graaf, Winette T.A. van der; Korte, Maarten A. de; Jonkman, S.; Kosterink, Jos G. W.; Veldhuisen, Dirk J. van; Sleijfer, Dirk; Jager, Pieter L.; Vries, Elisabeth G.E. de

doi:10.1200/jco.2005.03.8448

Cited by 267 publications

(182 citation statements)

References 21 publications

Supporting

Mentioning

164

Contrasting

Unclassified

Order By: Relevance

“…However, current in vivo imaging techniques, including X-ray, computerised axial tomography, ultrasound, nuclear imaging, and magnetic resonance imaging, do not have the ability to detect specific cancer cell proteins that serve as molecular targets. Investigational studies utilising positron emission tomography and scintigraphy have shown that it is possible to detect HER2 and ER in vivo (Linden et al, 2006;Perik et al, 2006), and an increased need to visualise these tumour targets is apparent as targeted therapies against specific molecules in cancer are rapidly developing.…”

Section: Discussionmentioning

confidence: 99%

Fluorescent tumour imaging of type I IGF receptor in vivo: comparison of antibody-conjugated quantum dots and small-molecule fluorophore

Zhang

Zeng

et al. 2009

Br J Cancer

View full text Add to dashboard Cite

BACKGROUND: The type I insulin-like growth factor receptor (IGF1R) is a transmembrane tyrosine kinase involved in cancer proliferation, survival, and metastasis. METHODS: In this study, we used two different fluorescent technologies (small-molecule fluorophores and quantum dot (QD) nanoparticles) to detect receptor expression and its downregulation by antibodies in vivo. RESULTS: After conjugation with AVE-1642, a humanised anti-IGF1R monoclonal antibody, both QDs (705 nm) or Alexa 680 (smallmolecule fluorophore) detected expression and downregulation of IGF1R in vitro. To examine their utility in vivo, either AVE-1642 conjugates were intravenously delivered to mice bearing xenograft tumours of mouse embryo fibroblasts expressing human IGF1R or MCF-7 human breast cancer cells. Quantum dot fluorescence was mainly localised to the reticuloendothelial system in several organs and engulfed by macrophages, with only very small amount of QDs detected in the xenograft tumours. Depletion of macrophages by clodronate liposomes did not alter the nonspecific uptake of QDs. In contrast, AVE-1642-conjugated Alexa 680 solely targeted to xenograft tumour and was able to detect IGF1R downregulation, with little nonspecific targeting to other tissues or organs in mice. CONCLUSION: Taken together, our data suggest that small-molecule fluorophores, not QDs, are suitable to detect the expression and downregulation of IGF1R in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

Fluorescent tumour imaging of type I IGF receptor in vivo: comparison of antibody-conjugated quantum dots and small-molecule fluorophore

Zhang

Zeng

et al. 2009

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…Behr and co-workers (13) demonstrated that 111 In-labeled trastuzumab can help to select patients responding to antibody treatment, as well as predict cardiotoxicity. However, a later study (14) showed that only 45% of the tumors were detected by 111 In-trastuzumab. The lack of sensitivity could be explained by the low contrast, which is typical for intact immunoglobulins, characterized by slow tumor penetration and slow blood clearance.…”

Section: Introductionmentioning

confidence: 99%

Pre-clinical evaluation of [111In]-benzyl-DOTA-ZHER2:342, a potential agent for imaging of HER2 expression in malignant tumors

Orlova¹,

Tran²,

Widström³

et al. 2007

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Imaging of expression of human epidermal growth factor receptor type 2 (HER2) in breast carcinomas may help to select patients eligible for trastuzumab therapy. The Affibody molecule Z HER2:342 is a small (7-kDa) non-immunoglobulin affinity protein, which binds to HER2 with a picomolar affinity. Previously, a benzyl-DTPA conjugate of Z HER2:342 was labeled with 111 In and demonstrated good targeting in murine xenografts. We considered that the use of the macrocyclic chelator DOTA could increase the label stability and enhance a choice of nuclides, which could be used as a label for Z HER2:342 .

show abstract

“…Note that markers can be both prognostic and predictive, as is the case, for ER and HER2 expression. Examples of molecular imaging paralleling these tissue-based assays are emerging using PET ER imaging (30,31), PET or MR imaging of 5-FU (32,33), and SPECT and PET imaging of HER2 expression (34,35). Recent data from our center illustrate the use of 18 F-fluorestradiol (FES) PET to image ER expression in metastatic breast cancer as a predictor of response to salvage endocrine therapy (Figure 4).…”

Section: Examples Of Tissue-based Assays Include the Expression Of Ermentioning

confidence: 99%

Molecular Imaging Research in the Outcomes Era

et al. 2007

View full text Add to dashboard Cite

SummaryAdvances in molecular imaging, combined with the goal of personalized cancer therapy, call for new approaches to clinical study design for trials testing imaging to guide therapy. The role of cancer imaging must expand and move beyond tumor detection and localization to incorporate quantitative evaluation of regional tumor phenotype. Imaging study design and outcome analysis must move beyond metrics designed to measure the performance for detection to include measures of prognosis, prediction of therapeutic success, and early therapy response. This implies changes in how studies are carried and out, and importantly in the regulatory oversight of cancer imaging. Demonstration that a biochemical or molecular imaging method correctly and accurately measures a specific biologic feature should be sufficient for approval for clinical trials. It may be possible that a combination of imaging procedures known to accurately depict tumor phenotype may be prognostic, even if the individual study cannot be directly validated against patient outcomes. Therefore, it will be important to be able to apply a range of possible imaging studies to different targeted cancer therapy trials. Academia and industry must work together with regulatory agencies and payers to facilitate well designed clinical studies, with appropriate outcome measures, to test the effectiveness of imaging in helping to direct cancer therapy. These will assure the appropriate use of imaging to direct treatment and make an important step towards individualized cancer therapy.

show abstract

Indium-111–Labeled Trastuzumab Scintigraphy in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

Abstract: Radiolabeled trastuzumab scintigraphy was not valuable in predicting trastuzumab-related cardiotoxicity in metastatic breast cancer patients, but can identify HER2-positive tumors. Measurement of plasma NT-proBNP is promising regarding prediction of trastuzumab-related cardiotoxicity.

Cited by 267 publications

References 21 publications

Fluorescent tumour imaging of type I IGF receptor in vivo: comparison of antibody-conjugated quantum dots and small-molecule fluorophore

Fluorescent tumour imaging of type I IGF receptor in vivo: comparison of antibody-conjugated quantum dots and small-molecule fluorophore

Pre-clinical evaluation of [111In]-benzyl-DOTA-ZHER2:342, a potential agent for imaging of HER2 expression in malignant tumors

Molecular Imaging Research in the Outcomes Era

Contact Info

Product

Resources

About