An analysis of imaging and biological effects impacting theranostic dosimetry using radiopharmaceutical pairs
Abstract:
Radiopharmaceutical therapy (RPT) is a safe and effective cancer treatment using alpha or beta emitting radiopharmaceuticals that specifically target cancer cells to selectively destroy cancer tissue while sparing healthy cells. Treatment can be personalized on a patient-by-patient basis using dosimetry to determine suitable administered activities for subsequent treatment cycles. Dosimetry requires obtaining quantitative single photon emission computed tomography (SPECT) images which can only be done using gamma emitting radioisotopes.
Not all therapeutic radioisotopes are suitable for SPECT imaging. In such cases, it may be necessary to use an imaging surrogate to predict the radiation dose from the therapeutic isotope, either pre-therapy or during combination RPT. However, these methods may introduce inaccuracies into the dosimetry estimate. This dissertation aims to investigate some “theranostic pair” radiopharmaceuticals and determine if these pairs may be suitable for theranostic dosimetry.
In addition to a comprehensive literature review of theranostic dosimetry and the validity of multiple theranostic pairs used clinically and pre-clinically, three Monte Carlo based simulation studies are
performed:
- First, an investigation into the theranostic pair 177Lu (a beta/gamma
emitter) and 90Y (a beta emitter) to determine if Bremstrahhlung photons emitted by 90Y reduce the accuracy of quantitative SPECT imaging of 177Lu
- Then, simulations of 225Ac (an alpha emitter) and 177Lu within prostate cancer cells were performed and used to create nucleus absorbed dose kernels which were convolved with multicellular tumour maps of varying morphologies (i.e. hypoxic, necrotic, and normoxic tumour
phenotypes) to assess the absorbed dose distribution differences between particulate radiation from 225Ac and 177Lu on a microscopic scale
- Finally, the proposition of a novel method using 99mTc (a gamma
emitter) to improve bone marrow dosimetry is discussed and tested. Bone marrow dosimetry during RPT for prostate cancer with 177Lu labelled pharmaceuticals is extremely challenging, and we propose using 99mTc-sulfur colloids to assist in the determination of bone marrow location during imaging and subsequently use 177Lu for bone marrow dosimetry, which requires simultaneous SPECT imaging of 177Lu and 99mTc.
We test the feasibility of this and suggest additions to clinical scatter correction methods to reduce the impact of photon contamination from 177Lu on 99mTc images.