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177 Lu-DOTATATE therapy has been shown to produce encouraging results in treatment of neuroendocrine tumours (NETs). Unfortunately, since dosimetry for radionuclide therapy is considered to be challenging, typically similar amount of radiopharmaceutical is administered to every patient. There is growing evidence that the efficacy of this therapy can be significantly improved by employing personalized protocols, based on the organ-at-risk dosimetry. The aim of this study is to propose a practical and accurate dosimetry protocol based on the simplified acquisition schedules. Data from fifty-three therapy cycles in thirty-nine NET patients were analyzed. Three SPECT/CT scans, acquired at 4 h (D0), 23 h (D1) and 70 h (D3) after injection, were performed. The kidney volume was determined using CT and the activity was determined from quantitative SPECT using an iterative thresholding method. For each dataset, four methods were used to model the time-activity-curves (TAC): M1-two trapezoid segments (0 to D0 and D0 to D1), followed by monoexponential fit to D1  +  D3 data; M2-monoexponential fit to D0  +  D1  +  D3 data; M3 and M4-monoexponential fit to D0  +  D3 and D1  +  D3 data, respectively. Additionally, kidney doses obtained from single time point method using a monoexponential curve with the population mean effective half-life, normalized to activities at D0 or D1 or D3 points, were calculated. The accuracy of simplified dosimetry methods was assessed as the percentage difference relative to doses calculated from M1. The major contribution to the absorbed dose estimate comes from the area under the late time portion of the TAC (D1 to infinity). Therefore, information from the late scan (D3) is crucial for the determination of kidney absorbed doses. Single time point method using monoexponential TAC, with the population mean effective half-life normalized to the late data point (48-72 h for kidneys) produces  <10% deviation in the absorbed dose estimation, thus is recommended for clinical use.

A common form of treatment for patients with hepatocellular carcinoma (HCC) is transarterial radioembolization (TARE) with non-degradable glass or resin microspheres (MS) labeled with 90 Y ( 90 Y-MS). To further simplify the dosimetry calculations in the clinical setting, to have more control over the particle size and to change the permanent embolization to a temporary one, we developed uniformly-sized, biodegradable 188 Re-labeled MS ( 188 Re-MS) as a new and easily imageable TARE agent. Methods: MS made of poly( L -lactic acid) were produced in a flow focusing microchip. The MS were labeled with 188 Re using a customized kit. An orthotopic HCC animal model was developed in male Sprague Dawley rats by injecting N1-S1 cells directly into the liver using ultrasound guidance. A suspension of 188 Re-MS was administered via hepatic intra-arterial catheterization 2 weeks post-inoculation of the N1-S1 cells. The rats were imaged by SPECT 1, 24, 48, and 72 h post-radioembolization. Results: The spherical 188 Re-MS had a diameter of 41.8 ± 6.0 µm ( CV = 14.5%). The site and the depth of the injection of N1-S1 cells were controlled by visualization of the liver in sonograms. Single 0.5 g tumors were grown in all rats. 188 Re-MS accumulated in the liver with no deposition in the lungs. 188 Re decays to stable 188 Os by emission of β ¯ particles with similar energy to those emitted by 90 Y while simultaneously emitting γ photons, which were imaged directly by single photon computed tomography (SPECT). Using Monte Carlo methods, the dose to the tumors was calculated to be 3-6 times larger than to the healthy liver tissue. Conclusions: 188 Re-MS have the potential to become the next generation of β ¯ -emitting MS for TARE. Future work revolves around the investigation of the therapeutic potential of 188 Re-MS in a large-scale, long-term preclinical study as well as the evaluation of the clinical outcomes of using 188 Re-MS with different sizes, from 20 to 50 µm., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.