Recent advances in cancer immunotherapy imaging: diagnosis and treatment

Recent advances in cancer immunotherapy imaging: diagnosis and treatment

Trending now! As illustrated in the following graph, research interest in the field of immunotherapy is growing exponentially (source: Select Biosciences Ltd, UK).

Users of MILabs’ VECTor PET/SPECT/OI/CT imaging platform demonstrate that the system offers a full panel of molecular imaging techniques for immunotherapy research. The combined imaging offered by the platform’s integrated multimodal capabilities and its exclusive omni-tomography synergies enable for the first time, a comprehensive evaluation of novel pharmaceuticals and tumor responses to given therapies.

Ultra-high-resolution SPECT/CT for imaging of heterogeneity of the tumor microenvironment

In vivo imaging of pro- and antitumoral cellular components of the tumor micro-environment has long been hampered by the limited resolution of molecular imaging modalities. With MILabs’ ultra-high 120-micron resolution SPECT, it is now possible to track in 3D, the heterogeneous effect of immunotherapy on tumors, whether using antibodies, oncolytic viruses, or T-cell activity. In fact, U-SPECT was the first system used to illustrate were T-cells were hiding in various tumors by detecting PD-L1 expression levels.

Further reading: Left image: Branderhorst et al, Three-dimensional histologic validation of high-resolution SPECT of antibody distributions within xenografts, J Nucl Med, 2014 Right top image: Miller et al, The use of the NIS reporter gene for optimizing oncolytic virotherapy, Expert Opin Biol Ther, 2016 Right bottom image: Heskamp et al, Noninvasive imaging of tumor PD-L1 expression using radiolabeled anti–PD-L1 antibodies, Cancer Res, 2015

Simultaneous imaging of co-administered PET and SPECT tracers for a better understanding of cancer biology

With the MILabs VECTor one can simultaneously image co-injected PET and SPECT tracers at sub-mm resolution. Such high-resolution coincident imaging of e.g., vascularity and hypoxia (left image), enables to study the combined effect of antiangiogenic, antivascular, and antihypoxia therapies on tumors, while the right image illustrates that simultaneous PET/SPECT imaging can augment our understanding of the non-specific uptake of radiolabeled immunotherapy antibodies, and reveal tumor heterogeneity with PET.

Further reading: Left image: Adachi et al , In vivo simultaneous imaging of vascular pool and hypoxia with a HT-29 tumor model: the application of dual-isotope SPECT/PET/CT, IJSBAR, 2017 Right image: Knight et al , Dual-isotope imaging allows in vivo immunohistochemistry using radiolabelled antibodies in tumours, Nucl Med Biol, 2019

3D DCE-CT imaging of tumor angiogenesis and targeted CE-CT, molecular CT and radiotherapy imaging

The ultra-high-resolution U-CT system allows highly accurate quantification of relative blood volume (rBV) and detailed 3D analysis of the vascular network in tumors (top). DCE-CT can further be combined with dual-energy CT acquisitions to enhance contrast further or discriminate between two contrast agents. Targeted CE-CT is possible by a new agent with high iodine content cRGD-PThyN for imaging lung tumors (below). A facile iodine exchange reaction enables the use of ¹²³I or ¹²⁴I for SPECT and PET imaging, or ¹³¹I for radiotherapy imaging, all at sub-mm resolution (bottom right).

Further reading: Top images: Scientist in the spotlight: Dr. Veerle Kersemans, Imaging Core, Department of Oncology of the University of Oxford, MILabs Bottom images: Gu et al , Nanoagents based on poly(ethylene glycol)-b-poly(l-thyroxine) block copolypeptide for enhanced dual-modality imaging and targeted tumor radiotherapy, Small, 2019

Multimodal oncoviral and T-cell therapy imaging, from basic research to clinical-compliant imaging

MILabs’ Broadband Photon Tomography provides a significant advancement for studying oncolytic virus and CAR-T cell therapy by combining optical and nuclear tomography for studying both deep orthopedic and subcutaneous tumors. Moreover, a wide-variety of clinically compliant techniques can be used for imaging oncolytic viruses or CAR-T cells expressing hNIS : ¹²³I or ^99mTc for SPECT, positron-range-free ¹²⁴I or ¹⁸F-TFB for PET, and ¹³¹I or ¹⁸⁸Re for radiotherapy. Plus, simultaneous imaging of PET/SPECT and PET/Radiotherapy tracers accelerates translation to the clinic.

Further reading: Hage et al, Comparison of the accuracy of FMT/CT and PET/MRI for the assessment of antibody biodistribution in squamous cell carcinoma xenografts, J Nucl Med, 2017 Miller et al, Perfusion pressure is a critical determinant of the intratumoral extravasation of oncolytic viruses, Molecular Therapy, 2016 Miller et al, the use of the NIS reporter gene for optimizing oncolytic virotherapy, Expert Opin Biol Ther, 2015

Sub-mm radio-immunotherapy (RIT) imaging using all alpha- and beta-emitting isotopes

With its wide radioisotope energy range (20-1000 keV) and sub-mm resolution imaging capabilities, MILabs’ VECTor is the only preclinical imaging platform allowing its users to exploit imaging of all tracers for targeted radiotherapy in mice. This includes most, if not all, known “single entity” radiotheranostic agents, including α- and β-emitting radionuclides conjugated to a wide range of biomolecules, antibodies, peptides, small-molecule inhibitors, and nanocarriers. ²²³Ra-dichloride has intrinsic bone-targeting properties.

Further reading: Ra-223: Abou et al , First whole-body three-dimensional tomographic imaging of alpha particle emitting Radium-223, bioRxiv, 2018 Lu-177: Kuo et al , Enhancing treatment efficacy of ¹⁷⁷Lu-PSMA-617 with the conjugation of an albumin-binding motif: preclinical dosimetry and endoradiotherapy studies, Molecular Pharmaceutics, 2018 Re-188: Esquinas et al , ¹⁸⁸Re image performance assessment using small animal multi-pinhole SPECT/PET/CT system, Physica Medica, 2017 At-209: Crawford et al , Evaluation of ²⁰⁹At as a theranostic isotope for ²⁰⁹At-radiopharmaceutical development using high-energy SPECT, Phys Med Biol, 2018 I-131: D’Huyvetter et al , ¹³¹I-labeled anti-HER2 camelid sdAb as a theranostic tool in cancer treatment, Clin Cancer Res, 2017 Bi-131: De Swart et al , Utilizing high-energy γ-photons for high-resolution ²¹³Bi SPECT in mice, J Nucl Med, 2016 Ac-225: Robertson et al , Multi-isotope SPECT imaging of the ²²⁵Ac decay chain: feasibility studies, Phys Med Biol, 2017

Deep-tissue and translational nanomedicine imaging with optical/CT and nuclear/CT tomography

In nanomedicine, carrier materials with a size of 1-100 nm are employed to improve tumor uptake and biodistribution of administered therapeutic drugs. The VECTor platform enables researchers to use both optical probes and nuclear tracers for nanomedicine applications. Dual-labeled optical/nuclear probes facilitate translation of nanomedicines from bench to clinic without changing nanocarriers (left). The effect of nanoparticle size and tumor EPR can be studied with both optical FLT and nuclear PET or SPECT (right). FLT quantitation and correlation with PET is excellent, even for deep tissue imaging.

Further reading: Left image: Rosenhain et al , Validation of fluorescence-mediated tomography combined with micro-CT: a longitudinal in vivo comparison to PET-imaging, WMIC, 2019 Right image: Schmitt et al , Quantitative SPECT imaging and biodistribution point to molecular weight independent tumor uptake for some long-circulating polymer nanocarriers, RSC Adv, 2018

Evaluating novel tracers for early detection of immunotherapy response

MILabs’ VECTor multimodal synergy provides an excellent toolbox for evaluating novel probes for early immunotherapy response detection. Translating from optical to nuclear tracers can be done on the same platform, under the same physical and physiological conditions. One-to-one translation from SPECT to PET, or Radiotherapy, is virtually seamless thanks to simultaneous exclusive multi-isotope imaging. This is illustrated by comparing early apoptosis detection with ^99mTc-duramicin that is nearly undetected by ¹⁸F-FDG (left), and novel tracer development for macrophage imaging (right).

Further reading: Left image: Li et al , [^99mTc]Tc-duramycin, a potential molecular probe for early prediction of tumor response after chemotherapy, Nuc Med Bio, 2018 Right image: Terry et al , ¹ ¹¹In-anti-F4/80-A3-1 antibody: a novel tracer to image macrophages, Eur J Nucl Med Mol Imaging, 2015

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