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Abstract

Radiopharmaceutical therapies (RPTs) have demonstrated promising safety and efficacy in treating multiple types of cancer. Theranostics (𝒕𝒉𝒆𝒓𝒂py + diag𝒏𝒐𝒔𝒕𝒊𝒄𝒔) is the combination of imaging and therapy to personalize patient treatment using dosimetry. Not all therapeutic radioisotopes can be imaged accurately with single photon emission computed tomography (SPECT), which is necessary for dosimetry. In such cases, a second radiopharmaceutical can be used as an imaging surrogate to predict the dose from the therapeutic radiopharmaceutical. This method (which can be referred to as "theranostic dosimetry") can introduce inaccuracies into dosimetry estimates. This dissertation aims to study some biological or imaging-based factors that can cause these inaccuracies for some theranostic pairs and determine if they can be overcome. First, a comprehensive review of theranostic dosimetry and the theranostic pairs that are used clinically/pre-clinically was performed, with an analysis of the existing literature to determine if each pair is suitable for theranostic dosimetry. Then, ¹⁷⁷Lu and three possible theranostic pair radionuclides were studied in more detail: first, an investigation into if ¹⁷⁷Lu can be imaged accurately in the presence of ⁹⁰Y with SPECT, which is necessary if ¹⁷⁷Lu is to be used as an imaging surrogate for ⁹⁰Y. Then, an analysis into the behaviour of ¹⁷⁷ and ²²⁵Ac charged particle emissions at the cellular level to assess dose deposition differences, which could impact the accuracy using ¹⁷⁷Lu as an imaging surrogate for ²²⁵Ac. Finally, an investigation into if ⁹⁹ᵐTc can be imaged in the presence of ¹⁷⁷Lu, which could enable bone marrow identification with ⁹⁹ᵐTc during RPT for prostate cancer with ¹⁷⁷Lu as the therapeutic radionuclide to improve bone marrow dosimetry estimates. Results showed that accurately imaging ¹⁷⁷Lu in the presence of ⁹⁰Y and ⁹⁹ᵐTc in the presence of ¹⁷⁷Lu is possible, and therefore imaging-based factors are unlikely to impact theranostic dosimetry estimates with these pairs. Differences on the cellular level between emissions from ²²⁵Ac and ¹⁷⁷Lu were found, indicating a one-size-fits-all dose extrapolation from ¹⁷⁷Lu to ²²⁵Ac may omit important information. Finally, while biological differences may exist between radiopharmaceutical pairs, dosimetry may still result in improved patient outcomes.