18F-nanobody for PET imaging of HER2 overexpressing tumors

Xavier, Catarina; Blykers, Anneleen; Vaneycken, Ilse; D’Huyvetter, Matthias; Heemskerk, J.F.; Lahoutte, Tony; Devoogdt, Nick; Caveliers, Vicky

doi:10.1016/j.nucmedbio.2016.01.002

Cited by 99 publications

(114 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The same HER2-targeting sdAb was also 18 F-labeled and tested preclinically, with a high tumor-toblood ratio (13 6 2 as early as 1 h after injection). Uptake in the kidneys was, however, only half that measured for 68 Galabeled 2Rs15d (8) and thus might further decrease the radiation exposure. Finally, 2Rs15d was successfully radiolabeled with 131 I and showed superior tumor uptake and remarkably low kidney retention in HER2-positive tumor xenografted mice (9).…”

Section: Sdabs In Radionuclide Imagingmentioning

confidence: 79%

Same-Day Imaging Using Small Proteins: Clinical Experience and Translational Prospects in Oncology

Krasniqi¹,

D’Huyvetter²,

Devoogdt³

et al. 2018

J Nucl Med

Self Cite

106

View full text Add to dashboard Cite

Imaging of expression of therapeutic targets may enable stratification of patients for targeted treatments. The use of small radiolabeled probes based on the heavy-chain variable region of heavy-chain-only immunoglobulins or nonimmunoglobulin scaffolds permits rapid localization of radiotracers in tumors and rapid clearance from normal tissues. This makes high-contrast imaging possible on the day of injection. This mini review focuses on small proteins for radionuclide-based imaging that would allow same-day imaging, with the emphasis on clinical applications and promising preclinical developments within the field of oncology.

show abstract

Section: Sdabs In Radionuclide Imagingmentioning

confidence: 79%

Same-Day Imaging Using Small Proteins: Clinical Experience and Translational Prospects in Oncology

Krasniqi¹,

D’Huyvetter²,

Devoogdt³

et al. 2018

J Nucl Med

Self Cite

106

View full text Add to dashboard Cite

show abstract

“…With regard to the effect of radionuclide and labeling method on these parameters, we note that in a previous study with 5F7 (with a cys-tag) labeled using [ 125 I]SGMIB, intracellular retention in this cell line was maintained at about 60 % for up to 24 h as was the case with another residualizing radioiodination agent [36]. The 2Rs15d sdAb has been radiolabeled with several radionuclides including F-18 [18], Ga-68 [24], Tc-99m [23], and Lu-177 [38, 39]; however, these publications did not include internalization experiments for comparison to the current study.…”

Section: Discussionmentioning

confidence: 99%

“…Their molecular weight (12–15 kDa), a tenth of intact antibodies, facilitates deeper tumor penetration compared with intact antibodies. A significant advantage for PET imaging applications is that their fast blood clearance makes them compatible for use with clinically amenable short-lived positron emitters F-18 and Ga-68 [17, 18]. …”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, this compromises its potential utility in radiolabeled form as a PET agent for evaluating response to trastuzumab therapy as it will not be able to differentiate, for example, between low tumor uptake due to HER2 blocking by circulating trastuzumab and receptor downregulation [22]. An intriguing approach that circumvents this problem would be to utilize 2Rs15d, identified from a panel of anti-HER2 sdAbs [23] as a molecule with good affinity and tumor targeting but recognizing a different epitope on HER2 from those targeted by the clinically relevant therapeutic antibodies trastuzumab and pertuzumab [18, 24]. …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fluorine-18 Labeling of the HER2-Targeting Single-Domain Antibody 2Rs15d Using a Residualizing Label and Preclinical Evaluation

et al. 2017

Self Cite

View full text Add to dashboard Cite

Purpose Our previous studies with F-18-labeled anti-HER2 single-domain antibodies (sdAbs) utilized 5F7, which binds to the same epitope on HER2 as trastuzumab, complicating its use for positron emission tomography (PET) imaging of patients undergoing trastuzumab therapy. On the other hand, sdAb 2Rs15d binds to a different epitope on HER2 and thus might be a preferable vector for imaging in these patients. The aim of this study was to evaluate the tumor targeting of F-18 -labeled 2Rs15d in HER2-expressing breast carcinoma cells and xenografts. Procedures sdAb 2Rs15d was labeled with the residualizing labels N-succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ([18F]RL-I) and N-succinimidyl 4-guanidinomethyl-3-[125I]iodobenzoate ([125I]SGMIB), and the purity and HER2-specific binding affinity and immunoreactivity were assessed after labeling. The biodistribution of I-125- and F-18-labeled 2Rs15d was determined in SCID mice bearing subcutaneous BT474M1 xenografts. MicroPET/x-ray computed tomograph (CT) imaging of [18F]RL-I-2Rs15d was performed in this model and compared to that of nonspecific sdAb [18F]RL-I-R3B23. MicroPET/CT imaging was also done in an intracranial HER2-positive breast cancer brain metastasis model after administration of 2Rs15d-, 5F7-, and R3B23-[18F]RL-I conjugates. Results [18F]RL-I was conjugated to 2Rs15d in 40.8 ± 9.1 % yield and with a radiochemical purity of 97–100 %. Its immunoreactive fraction (IRF) and affinity for HER2-specific binding were 79.2 ± 5.4 % and 7.1 ± 0.4 nM, respectively. [125I]SGMIB was conjugated to 2Rs15d in 58.4 ± 8.2 % yield and with a radiochemical purity of 95–99 %; its IRF and affinity for HER2-specific binding were 79.0 ± 12.9 % and 4.5 ± 0.8 nM, respectively. Internalized radioactivity in BT474M1 cells in vitro for [18F]RL-I-2Rs15d was 43.7 ± 3.6, 36.5 ± 2.6, and 21.7 ± 1.2 % of initially bound radioactivity at 1, 2, and 4 h, respectively, and was similar to that seen for [125I]SGMIB-2Rs15d. Uptake of [18F]RL-I-2Rs15d in subcutaneous xenografts was 16–20 %ID/g over 1–3 h. Subcutaneous tumor could be clearly delineated by microPET/CT imaging with [18F]RL-I-2Rs15d but not with [18F]RL-I-R3B23. Intracranial breast cancer brain metastases could be visualized after intravenous administration of both [18F]RL-I-2Rs15d and [18F]RL-I-5F7. Conclusions Although radiolabeled 2Rs15d conjugates exhibited lower tumor cell retention both in vitro and in vivo than that observed previously for 5F7, given that it binds to a different epitope on HER2 from those targeted by the clinically utilized HER2-targeted therapeutic antibodies trastuzumab and pertuzumab, F-18-labeled 2Rs15d has potential for assessing HER2 status by PET imaging after trastuzumab and/or pertuzumab therapy.

show abstract

“…37,38 To overcome the current limitation, a series of radiopharmaceuticals assembled with antibodies, nanobodies or affibodies have been developed and some of these are already under clinical evaluation for use as PET or SPECT nuclear imaging agents for in vivo molecular detection of HER2 receptor. 39,40 This study describes the use of a multifunctional NP system, able to act as a SPECT radiotracer for tumor detection and opening the opportunity to develop a new generation of theranostic nanoagents to be used for noninvasive detection of HER2 + cells and targeted drug delivery. 41,42 In fact, although chemotherapy in combination with TZ administration has been reported to play an important role in the treatment of HER2 + BC, about 70% of patients demonstrated resistance.…”

Section: Discussionmentioning

confidence: 99%

Development of<sup> 99m</sup>Tc-radiolabeled nanosilica for targeted detection of HER2-positive breast cancer

Rainone¹,

Riva²,

Belloli³

et al. 2017

IJN

View full text Add to dashboard Cite

The human epidermal growth factor receptor 2 (HER2) is normally associated with a highly aggressive and infiltrating phenotype in breast cancer lesions with propensity to spread into metastases. In clinic, the detection of HER2 in primary tumors and in their metastases is currently based on invasive methods. Recently, nuclear molecular imaging techniques, including positron emission tomography and single photon emission computed tomography (SPECT), allowed the detection of HER2 lesions in vivo. We have developed a 99m Tc-radiolabeled nanosilica system, functionalized with a trastuzumab half-chain, able to act as drug carrier and SPECT radiotracer for the identification of HER2-positive breast cancer cells. To this aim, nanoparticles functionalized or not with trastuzumab half-chain, were radiolabeled using the 99m Tc-tricarbonyl approach and evaluated in HER2 positive and negative breast cancer models. Cell uptake experiments, combined with flow cytometry and fluorescence imaging, suggested that active targeting provides higher efficiency and selectivity in tumor detection compared to passive diffusion, indicating that our radiolabeling strategy did not affect the nanoconjugate binding efficiency. Ex vivo biodistribution of 99m Tc-nanosilica in a SK-BR-3 (HER2 + ) tumor xenograft at 4 h postinjection was higher in targeted compared to nontargeted nanosilica, confirming the in vitro data. In addition, viability and toxicity tests provided evidence on nanoparticle safety in cell cultures. Our results encourage further assessment of silica 99m Tc-nanoconjugates to validate a safe and versatile nanoreporter system for both diagnosis and treatment of aggressive breast cancer.

show abstract

18F-nanobody for PET imaging of HER2 overexpressing tumors

Cited by 99 publications

References 52 publications

Same-Day Imaging Using Small Proteins: Clinical Experience and Translational Prospects in Oncology

Same-Day Imaging Using Small Proteins: Clinical Experience and Translational Prospects in Oncology

Fluorine-18 Labeling of the HER2-Targeting Single-Domain Antibody 2Rs15d Using a Residualizing Label and Preclinical Evaluation

Development of<sup> 99m</sup>Tc-radiolabeled nanosilica for targeted detection of HER2-positive breast cancer

Contact Info

Product

Resources

About