Single domain antibodies (sdAbs) fulfill the requisites of an ideal probe for successful molecular imaging. Radiolabeled sdAbs are already used in several contexts, such as to evaluate breast cancer diagnosis in a preclinical setting, to discriminate between moderate and high epidermal growth factor receptor expression for the improved prognosis of cancer therapy, and to monitor the status of inflammatory responses by visualizing dendritic cells. Creative Biolabs provides customized radiolabeled sdAb development services for molecular imaging. We will provide the solution according to your detailed analysis method and desired label.
Single-photon emission computed tomography (SPECT) is based on γ-rays and sdAbs are linked to radionuclides such as 99mTc, 177Lu, 123I and 111In. These γ-rays are recorded by the detectors of a dedicated γ-camera or SPECT instrument, which can be converted into an image upon signal processing to pinpoint the localization of the radiolabeled sdAb. When using β-emitting radioisotopes such as 131I and 177Lu, a therapeutic effect can also be pursued by their ionization and DNA damaging activity. Such a radionuclide-based construct enabling both imaging and therapeutic use is termed theranostic.
Table.1 Currently approved targeted radionuclide therapies in oncology. (D' Huyvetter, 2014)
Indication | Product | Physical half-life (days) | Emission | Path length (mm) |
Thyroid cancer | 131I | 8.04 | β, γ | 4 |
Thyroid cancer | 131I | 8.04 | β, γ | 4 |
Neuroblastoma | 177Lu-octreotide | 6.72 | β, γ | 1 |
Neuroblastoma | 90Y-octreotide | 2.7 | β | 12 |
Non-Hodgkin's lymphoma | 90Y-ibritumomab tiuxetan | 2.7 | β | 12 |
Non-Hodgkin's lymphoma | 131I-tositumomab | 8.04 | β, γ | 4 |
Liver metastases | 90Y-microspheres | 2.7 | β | 12 |
Neuroblastoma | 131I-MIBG | 8.04 | β, γ | 4 |
Bone metastases | 153Sm-EDTMP | 1.95 | β, γ | 3.1 |
Bone metastases | 89Sr-chloride | 50.5 | β | 8 |
Bone metastases | 223Ra-chloride | 11.4 | a | 0.5 |
On the other hand, the positron-emitting radioisotopes 18F, 68Ga, 124I or 89Zr have normally used for positron emission tomography (PET) purposes. Among them, the PET isotopes 18F and 68Ga are particularly suited to imaging with sdAbs due to their short half-lives (68 and 110 min, respectively), which match up well with the biological half-life of sdAbs. PET has greater advantages over SPECT concerning sensitivity and resolution. At present, most of the literature reports on radionuclide-based imaging with sdAbs have used 99mTc for SPECT imaging. Table. 2 shows sdAbs based probes in pre-clinical molecular imaging. The widespread interest in the use of 99mTc is primarily due to its excellent nuclear decay characteristics, viable coordination chemistry for radiolabeling different biomolecules and convenient availability from cost-effective 99Mo/99mTc generators. Moreover, due to the presence of the hexahistidine tag on the sdAb, it can easily be radiolabeled with 99mTc(CO)3 without any chemical modification of the protein.
Table.2 Overview of sdAbs based probes in pre-clinical molecular imaging. (Chakravarty, 2014)
Radiolabeled sdAbs hold great promise to play an important role in the development and implementation of personalized targeted therapy. There are apparent advantages of the use of radiolabeled sdAbs as companion diagnostics:
Creative Biolabs provides customized radiolabeled sdAbs for worldwide clients. Our custom products meet the following requirements:
Radio-immunodetection is a powerful method for evaluation of pharmacokinetics and target engagement in development of new biotherapeutics. We trust that radiolabeled sdAbs will have future potential as theranostic tools. If you are interested in our customized labeled nano-tracer development services, please directly contact us for more information.
References
For Research Use Only.