Optimising Molecular Radionuclide Therapy: The Role of Quantitative SPECT/CT & PET/CT and Radiation Dosimetry

Student thesis: Doctoral ThesisDoctor of Philosophy


Molecular radiotherapy (MRT) describes the use of radiopharmaceuticals to treat benign and malignant diseases. For practical reasons, MRT is conventionally prescribed as a standard administered activity regardless of differences in disease burden, disease distribution and physiology between individuals. If post-treatment imaging is performed, this is usually undertaken 24-48 hours after MRT administration, which limits the reliability of dose estimates and results in patients being provided with generic radiation safety advice. Optimising the outcome of MRT requires reliable measurement of absorbed radiation doses delivered to target tissues and healthy organs, and, from the patients’ perspective, the provision of tailored radiation protection advice particularly for therapies that account for a high percentage of treatments such as [131I] NaI-Sodium iodide and [177Lu] Lu - DOTA-TATE.

This study aims to investigate:
• The comparative results of quantitative SPECT/CT & PET/CT imaging.
• Whether serial changes in PET and SPECT-derived standardised uptake value (SUV) are correlated in patients undergoing MRT.
• Whether combining data from early (quantitative imaging) and late (whole-body-retention data) could support individual treatment planning for patients undergoing repeated cycles of MRT.
• Whether current MRT radiation protection advice is appropriate.

1. 2D/3D-Quantitative Optimisation and Validation
We examined multiple factors to achieve optimum quantitative 177Lu and 131I performance using:
a. A cylindrical homogeneous phantom was used to assess the scintillation camera calibration factor (CF) (cps/MBq).
b. A NEMA-IEC-Body Phantom incorporating six spheres of various sizes to calculate the concentration recovery coefficients (cRC).

2. PRRT Quantitative-SUV Assessment
We analysed retrospective data from 19 patients with histologically confirmed, unresectable metastatic NETs treated with PRRT over 4 cycles. SUVmax, lesion-to-liver (LTL) and lesion-to-spleen (LTS) ratios were measured using 68Ga-PET/CT and 177Lu-SPECT/CT images.

3. Patient-Led Whole-Body-Retention and Tailored Radiation Restrictions
Patients undergoing molecular radionuclide therapy using [177Lu] Lu- DOTA-TATE for PRRT and [131I] NaI for benign and malignant thyroid disease therapy were included. Planar whole-body images at 24-48 hr following MRT were acquired to assess early uptake. Patient-led whole-body retention measurements obtained using a hand-held radiation monitor were used to follow the time course of radioactivity clearance in each patient for four weeks post-therapy. For tailored radiation restriction calculation, bi-exponential fitting parameters were used for NET and DTC patients and mono-exponential parameters for Thyrotoxicosis patients.

HERMES-Hybrid3D-3.01 software was used to estimate CF and SUV values. 177Lu and 131I showed an optimal CF of 11.1 cps/MBq and 41cps/MBq, respectively, resulting in the most accurate activity. OSEM updates(iteration*subsets) for optimised activity concentration values was observed at 80-updates for 177Lu and 48-updates for 131I.

A significant correlation was shown between SPECT- and PET-derived SUV measurements (rs=0.8, p<0.01). The average SPECT-SUVmax at cycle-1 PRRT was comparable to PET-SUVmax at baseline pre-PRRT (30±24 and 35±18, respectively). Following PRRT, SPECT- and PET-derived SUVmax reduced by 45±29% and 34±27% respectively. LTS and LTL change showed a significant, robust positive linear correlation (rs=0.8, p<0.05) using both SPECT and PET.

A significant correlation was shown between patient-led and whole-body imaging derived whole-body retention (Ar) measurements (R=0.8, p<0.05) for all MRT groups. Patients showed variable restrictions to follow after MRT administration among the same group.

This study supports the following:
Quantitative-SUV estimates can be derived from I-131 and Lu-177 phantom SPECT/CT images and applied to clinical data.
Quantitative SPECT/CT was reliable in evaluating PRRT response and can be used as an early clinical response indicator between PRRT cycles.
Integrating patient-led radiation monitoring into MRT planning is feasible and is a valid dosimetry tool. The accuracy of this approach is comparable to that of serial quantitative imaging for whole-body activity estimates.
Tailored radiation restriction using patient-led whole-body retention measurements proved to be feasible to follow the time course of radioactivity clearance.
Date of Award1 Oct 2023
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorVal Lewington (Supervisor) & Lefteris Livieratos (Supervisor)

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