Intratherapeutic Biokinetic Measurements, Dosimetry Parameter Estimates, and Monitoring of Treatment Efficacy Using Cerenkov Luminescence Imaging in Preclinical Radionuclide Therapy

Timmermand, Oskar Vilhelmsson; Tran, Thuy; Strand, Sven‐Erik; Axelsson, Johan

doi:10.2967/jnumed.114.148544

Cited by 13 publications

(14 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When this imaging platform was extended to evaluate treatment regimens, it revealed low levels of AR pathway reactivation at suborgan resolution and enabled a comparison between models of surgical castration and castration plus adjuvant therapy. The agent may also be used to guide treatment in real time or assist in treatment delivery (42, 43). 89 Zr-11B6 targets tumorous lesions themselves, rather than sites of remodeling, and is able to identify both osteoblastic and osteoclastic metastases.…”

Section: Discussionmentioning

confidence: 99%

Internalization of secreted antigen–targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis

et al. 2016

Self Cite

View full text Add to dashboard Cite

Targeting the androgen receptor (AR) pathway prolongs survival in patients with prostate cancer, but resistance rapidly develops. Understanding this resistance is confounded by a lack of noninvasive means to assess AR activity in vivo. We report intracellular accumulation of a secreted antigen-targeted antibody (SATA) that can be used to characterize disease, guide therapy, and monitor response. AR-regulated human kallikrein-related peptidase 2 (free hK2) is a prostate tissue-specific antigen produced in prostate cancer and androgen-stimulated breast cancer cells. Fluorescent and radio conjugates of 11B6, an antibody targeting free hK2, are internalized and noninvasively report AR pathway activity in metastatic and genetically engineered models of cancer development and treatment. Uptake is mediated by a mechanism involving the neonatal Fc receptor. Humanized 11B6, which has undergone toxicological tests in nonhuman primates, has the potential to improve patient management in these cancers. Furthermore, cell-specific SATA uptake may have a broader use for molecularly guided diagnosis and therapy in other cancers.

show abstract

Section: Discussionmentioning

confidence: 99%

Internalization of secreted antigen–targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…As neuroblastomas represent a highly aggressive tumor entity that is difficult to assess by means of non-invasive imaging, we aimed to screen GD2-targeted monoclonal antibodies for target specificity. The basic characterization of specific antibody libraries is possible with PET; however, the use of a high-throughput modality like CLI enables timesaving screening assays both in vivo and in vitro [18]. …”

Section: Introductionmentioning

confidence: 99%

Correlation between positron emission tomography and Cerenkov luminescence imagingin vivoandex vivousing 64Cu-labeled antibodies in a neuroblastoma mouse model

et al. 2016

View full text Add to dashboard Cite

Antibody-based therapies gain momentum in clinical therapy, thus the need for accurate imaging modalities with respect to target identification and therapy monitoring are of increasing relevance. Cerenkov luminescence imaging (CLI) are a novel method detecting charged particles emitted during radioactive decay with optical imaging. Here, we compare Position Emission Tomography (PET) with CLI in a multimodal imaging study aiming at the fast and efficient screening of monoclonal antibodies (mAb) designated for targeting of the neuroblastoma-characteristic epitope disialoganglioside GD2. Neuroblastoma-bearing SHO mice were injected with a 64Cu-labeled GD2-specific mAb. The tumor uptake was imaged 3 h, 24 h and 48 h after tracer injection with both, PET and CLI, and was compared to the accumulation in GD2-negative control tumors (human embryonic kidney, HEK-293). In addition to an in vivo PET/CLI-correlation over time, we also demonstrate linear correlations of CLI- and γ-counter-based biodistribution analysis. CLI with its comparably short acquisition time can thus be used as an attractive one-stop-shop modality for the longitudinal monitoring of antibody-based tumor targeting and ex vivo biodistribution.These findings suggest CLI as a reliable alternative for PET and biodistribution studies with respect to fast and high-throughput screenings in subcutaneous tumors traced with radiolabeled antibodies. However, in contrast to PET, CLI is not limited to positron-emitting isotopes and can therefore also be used for the visualization of mAb labeled with therapeutic isotopes like electron emitters.

show abstract

“…Radioactive plaques containing iodine-125 or palladium-103 will not induce such light because these plaques emit gamma photons with lower energies than those of the Cerenkov threshold in tissue. 25,26 For the Cerenkov luminescence images acquired from Ru-106 plaques positioned in saline, the CLI radiance was found to depend linearly on the radioactivity normalized with the area of the plaque. This is in accordance with previous CLI studies of radionuclide uptake.…”

Section: Discussionmentioning

confidence: 99%

“…26,31 Such an approach could be applied for CLI during episcleral brachytherapy as well. However, in order to establish a truly quantitative CLI method, the collection efficiency (e.g., numerical aperture and camera quantum efficiency) needs to be taken into account in addition to rigorous calibration using plaques placed in saline and proper dose distribution calculations.…”

Section: Discussionmentioning

confidence: 99%

Cerenkov Luminescence Imaging for Accurate Placement of Radioactive Plaques in Episcleral Brachytherapy of Intraocular Tumors

Axelsson

Krohn

2015

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

Citation: Axelsson J, Krohn J. Cerenkov luminescence imaging for accurate placement of radioactive plaques in episcleral brachytherapy of intraocular tumors. Invest Ophthalmol Vis Sci. 2015;56:7362-7368. DOI:10.1167/iovs.15-18012 PURPOSE. The purpose of this study was to determine the feasibility of using Cerenkov luminescence imaging (CLI) to facilitate plaque placement during episcleral brachytherapy of intraocular tumors.METHODS. Ruthenium-106 (Ru-106) decays to rhodium-106, which in turn emits high-energy beta particles. When the electrons propagate through the eyewall, the so-called Cerenkov effect leads to emission of weak light, which can be captured by high-sensitivity chargecouple device (CCD) cameras. Enucleated porcine eyes were prepared with tumor phantoms made of melanin-containing gelatin. The anterior portion of the globe was removed, and different Ru-106 plaque types (designated CCA, CCB, COB, and CIA) with activities ranging from 6.8 to 16.7 MBq were sutured to the sclera overlying the tumor phantom. The globe was placed in a transparent container with saline. CLI was performed through the anterior opening of the eye using a cooled electron-multiplying CCD camera. RESULTS.Exposure times between 5 and 60 seconds produced good quality images of the Cerenkov light. There was a linear relationship between plaque activity and Cerenkov radiance. The perimeters of the CCA and CCB plaques could be seen clearly as circles of light symmetrically surrounding the tumor phantoms. Notched COB and CIA plaques led to images revealing their actual positions in relation to the optic disc and ciliary body, respectively. Simulated plaque tilting resulted in diffuse demarcation of the light.CONCLUSIONS. The study indicates that CLI is a feasible method to ensure accurate placement of Ru-106 plaques in brachytherapy of intraocular tumors. CLI may offer a new tool to improve and document plaque placement, both perioperatively and postoperatively.

show abstract

Intratherapeutic Biokinetic Measurements, Dosimetry Parameter Estimates, and Monitoring of Treatment Efficacy Using Cerenkov Luminescence Imaging in Preclinical Radionuclide Therapy

Cited by 13 publications

References 20 publications

Internalization of secreted antigen–targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis

Internalization of secreted antigen–targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis

Correlation between positron emission tomography and Cerenkov luminescence imagingin vivoandex vivousing 64Cu-labeled antibodies in a neuroblastoma mouse model

Cerenkov Luminescence Imaging for Accurate Placement of Radioactive Plaques in Episcleral Brachytherapy of Intraocular Tumors

Contact Info

Product

Resources

About