RDC as Imaging Tools

By conjugating cancer-targeted molecules with radionuclides for imaging, RDC can be used as a very important imaging tool in scientific research.

SPECT/PET Imaging

• The Importance of SPECT/PET Imaging
  Nuclear medicine images are produced by intravenous injection of short-lived radioactive isotopes into the animals, and then detecting their decay using a gamma camera, such as SPECT (Single Photon Emission Computed Tomography) or PET (Positron Emission) scanner, revealing the spatial and temporal distribution of target-specific radiotracers and pharmaceuticals. Even though both imaging modalities via RDC have a relatively low spatial resolution, the sensitivity of these two approaches is extremely high with subtle effects on experimental animals, which can reveal properties such as glucose metabolism, blood volume and flow, tissue uptake, receptor binding, and oxygen utilization.
• RDC for SPECT/PET Imaging
  As one essential part of RDC, the vector molecule, including antibody, small molecule, and peptide, can target specific molecules and gather at the targeting cells to image by PET or SPECT to visualize the specific molecular targets. As radiopharmaceutical probes, RDC is radiolabeled by different types of radioactive particles, ⁶⁴Cu, ⁶⁸Ga, ⁸⁹Zr for PET and ⁹⁹mTc, ²⁰¹Ti, ¹¹¹In for SPECT.

⁹⁹mTc- 3PRGD2 for Drug Evaluation

CM (Choroidal Melanoma) is a deadly malignancy with increasing incidence and burden worldwide, which may be caused by a variety of reasons, such as family history. The development of novel therapies for melanoma has received a great deal of attention. In order to more effectively evaluate the effects of novel drugs and therapies on CM, ⁹⁹mTc-PEG4-E[PEG4-c(RGDfK)]2 (⁹⁹mTc-3PRGD2), a novel RDC, is applied to clinical imaging via SPECT/CT with excellent quality in all 10 patients with a clear background, which is a key point for accuracy discrimination of CM lesions.

Fig.1 ⁹⁹mTc-3PRGD2 SPECT/CT images and CDFI images in a 78-year-old woman with CM. (Yan, B., et al., 2018, Medicine)

[⁶⁴Cu]DOTA-KJ1-26 mAbs for T Cell Labeling

T cells play an important role in inflammation, autoimmune diseases, and immunotherapy, of which the temporal distribution and homing dynamics in mammals are of special interest. A special RDC, ⁶⁴Cu-mAb (Monoclonal Antibody), can target the TCR (T Cell Receptor) and further radiolabel T cells for examination of the T cell migration kinetics, homing patterns, and the sites of T cell proliferation and activation to promote understanding of the T cell response in a non-invasive way.

Fig.2 Schematic principle of the in vitro labeling of cOVA-TCRtg-TH1 cells with cOVA-TCR–specific [⁶⁴Cu]DOTAKJ1-26 mAbs. (Griessinger, C. M., et al., 2015, Proc Natl Acad Sci U S A.)

References

1. Yan, B., Fu, T., Liu, Y., Wei, W., Dai, H., Fang, W., & Wang, F. (2018). ⁹⁹mTc-3PRGD2 single-photon emission computed tomography/computed tomography for the diagnosis of choroidal melanoma: A preliminary STROBE-compliant observational study. Medicine, 97(40).
2. Griessinger, C. M., Maurer, A., Kesenheimer, C., Kehlbach, R., Reischl, G., Ehrlichmann, W., ... & Kneilling, M. (2015). ⁶⁴Cu antibody-targeting of the T-cell receptor and subsequent internalization enables in vivo tracking of lymphocytes by PET. Proceedings of the National Academy of Sciences, 112(4), 1161-1166.