Dr Harry Marquis PhD
School of Physics, University of Sydney,
Nuclear Medicine Department, Royal North Shore Hospital, Sydney
and
Postdoctoral Researcher, Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY
Overview and problem statement
Single Photon Emission Computed Tomography (SPECT) is commonly used to evaluate the radiation dose delivered to target structures and normal organs in radionuclide therapy (RNT). SPECT imaging is hindered by poor spatial resolution, making it difficult to accurately quantify the dose delivered to target cancer lesions.
This has, in part, slowed the progress of personalising radionuclide therapies, where the dose is tailored to the individual based on pre-therapy diagnostic PET imaging. If one could improve the quantitative accuracy of SPECT imaging of RNT, it should lead to a better understanding of the radiobiological effects from the targeted radionuclide treatment and may pave the way further for a much more personalised treatment plan calculation for RNT.
The work in my thesis aimed to address the current limitations of SPECT imaging following RNT. The question asked was “Could we make use of pre-therapy diagnostic PET imaging to help us more accurately quantify the absorbed dose to target lesions following SPECT imaging of RNT?”.
In essence, we asked whether the theranostic principle could be exploited to make SPECT-based dosimetry estimates more accurate. To do this, we looked at applying an advanced reconstruction algorithm in a novel way, where diagnostic PET images are used in the reconstruction process to improve the image quality of the reconstructed SPECT image.
Radionuclide therapy and the Theranostic Principle
Radionuclide therapy involves the use of radionuclides as treatment agents, where the disease is targeted at a cellular or molecular level. It is ideal for the treatment of metastatic cancer that may otherwise not be easily treated with conventional radiation therapies such as external beam radiation therapy (EBRT). Radionuclide therapy is like chemotherapy in the sense that it is a systemic treatment but instead of using cytotoxic medications it uses molecules labelled with radionuclides to directly deliver DNA-killing radiation to the sites of the disease.
Radionuclide therapy is still in the stages of infancy compared to other mainstream treatment modalities such as EBRT, where EBRT has reached a high level of sophistication afforded by the maturity of the field. It is clear that the direct targeting afforded by RNT has clear advantages over conventional treatments, but significant progress is needed before it may be considered a mainstream cancer therapy.
Radionuclide therapy is most commonly administered using a “one size fits all” dose prescription approach, where patients typically receive the same standardised injected dose with limited modifications (if any) allowing for patient size, age, and extent of the metastatic disease.. The limited spatial resolution of SPECT imaging significantly impacts the ability to accurately quantify the absorbed radiation dose delivered to small target volumes and for this reason, tumor dosimetry is not routinely performed.
The term “theranostics”, is a combination of the terms “therapeutics” and “diagnostics”, and is used to describe a single molecule, peptide or other targeting agent that is used for both diagnostic imaging and RNT. Theranostics has recently become of significant interest in nuclear medicine, where diagnostic molecular imaging of the disease and RNT both use the same targeting ligand but with different radiolabels.
In practice, this typically translates to a positron-emitting radiolabel suitable for diagnostic PET imaging, where uptake and targeting of the disease is demonstrated, followed by a therapeutic radiolabel attached to the same targeting ligand, where alpha or beta emissions deliver radiation damage directly to the sites of the disease.
Therapeutic radiolabels typically also emit single gammas suitable for SPECT imaging, which is performed to monitor the therapy. Well-known examples are (i) the use of radioiodine (131I) to treat thyroid cancer and other thyroid disorders and (ii) the use of radioisotope labeled octreotate (or similar somatostatin receptor-targeting peptides) for the management of patients with neuroendocrine cancer.
For theranostics to reach its full potential, where the prescribed dose is tailored to the individual, there needs to be better concordance between PET and SPECT images. If diagnostic pre-therapy PET imaging could be used to maximise and optimise the delivery of therapeutic radionuclides, the management and treatment of a range of cancers, could be improved.
My thesis
The work in my thesis aimed at addressing the current limitations of SPECT imaging of therapeutic radionuclides by improving the spatial resolution of SPECT reconstructed images. To do this, we looked at using diagnostic PET images to guide the reconstruction of SPECT data using an advanced reconstruction algorithm. We call this SPECT reconstruction approach “SPECTRE”, that is, Single Photon Emission Computed Theranostic REconstruction. SPECTRE is the first example of PET-guided SPECT reconstructions and demonstrates potential for improved SPECT resolution and image quality, ultimately leading to more accurate SPECT-based dosimetry estimates.
Harry Marquis PhD, 9 February 2023
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Editor’s Comment
The research work above is very nicely described in this video presented by Harry Marquis as a Royal Society of NSW Scholarship winner, 2 February 2021.
Harry Marquis was awarded for this work the Society of Nuclear Medicine and Molecular Imaging’s 2020 Arthur M. Weis Prize “for outstanding original work in Radiation Safety and Dosimetry”.
For those wishing to read a more advanced account of Harry’s research methodology and results to date, then watch out for Harry’s next Better Healthcare Technology article:
“Towards personalised radionuclide therapy by improving the spatial resolution of SPECT imaging in a theranostic technique: Part 2, advanced research”.
