Comparison of radiobiological parameters for 90Y radionuclide therapy (RNT) and external beam radiotherapy (EBRT) in vitro.

BACKGROUND: Dose rate variation is a critical factor affecting radionuclide therapy (RNT) efficacy. Relatively few studies to date have investigated the dose rate effect in RNT. Therefore, the aim of this study was to benchmark 90Y RNT (at different dose rates) against external beam radiotherapy (EBRT) in vitro and compare cell kill responses between the two irradiation processes. RESULTS: Three human colorectal carcinoma (CRC) cell lines (HT29, HCT116, SW48) were exposed to 90Y doses in the ranges 1-10.4 and 6.2-62.3 Gy with initial dose rates of 0.013-0.13 Gy/hr (low dose rate, LDR) and 0.077-0.77 Gy/hr (high dose rate, HDR), respectively. Results were compared to a 6-MV photon beam doses in the range from 1-9 Gy with constant dose rate of 277 Gy/hr. The cell survival parameters from the linear quadratic (LQ) model were determined. Additionally, Monte Carlo simulations were performed to calculate the average dose, dose rate and the number of hits in the cell nucleus. For the HT29 cell line, which was the most radioresistant, the α/ß ratio was found to be ≈ 31 for HDR-90Y and ≈ 3.5 for EBRT. LDR-90Y resulting in insignificant cell death compared to HDR-90Y and EBRT. Simulation results also showed for LDR-90Y, for doses ≲ 3 Gy, the average number of hits per cell nucleus is ≲ 2 indicating insufficiently delivered lethal dose. For 90Y doses [Formula: see text] 3 Gy the number of hits per nucleus decreases rapidly and falls below ≈ 2 after ≈ 5 days of incubation time. Therefore, our results demonstrate that LDR-90Y is radiobiologically less effective than EBRT. However, HDR-90Y at ≈ 56 Gy was found to be radiobiologically as effective as acute ≈ 8 Gy EBRT. CONCLUSION: These results demonstrate that the efficacy of RNT is dependent on the initial dose rate at which radiation is delivered. Therefore, for a relatively long half-life radionuclide such as 90Y, a higher initial activity is required to achieve an outcome as effective as EBRT.

Accuracy of Dose Calibrators for 68Ga PET Imaging: Unexpected Findings in a Multicenter Clinical Pretrial Assessment.

We report the discovery of a systematic miscalibration during the work-up process for site validation of a multicenter clinical PET imaging trial using 68Ga, which manifested as a consistent and reproducible underestimation in the quantitative accuracy (assessed by SUV) of a range of PET systems from different manufacturers at several different facilities around Australia. Methods: Sites were asked to follow a strict preparation protocol to create a radioactive phantom with 68Ga to be imaged using a standard clinical protocol before commencing imaging in the trial. All sites had routinely used 68Ga for clinical PET imaging for many years. The reconstructed image data were transferred to an imaging core laboratory for analysis, along with information about ancillary equipment such as the radionuclide dose calibrator. Fourteen PET systems were assessed from 10 nuclear medicine facilities in Australia, with the aim for each PET system being to produce images within 5% of the true SUV. Results: At initial testing, 10 of the 14 PET systems underestimated the SUV by 15% on average (range, 13%-23%). Multiple PET systems at one site, from two different manufacturers, were all similarly affected, suggesting a common cause. We eventually identified an incorrect factory-shipped dose calibrator setting from a single manufacturer as being the cause. The calibrator setting for 68Ga was subsequently adjusted by the users so that the reconstructed images produced accurate values. Conclusion: PET imaging involves a chain of measurements and calibrations to produce accurate quantitative performance. Testing of the entire chain is simple, however, and should form part of any quality assurance program or prequalifying site assessment before commencing a quantitative imaging trial or clinical imaging.

68Ga-DOTATATE Breast Uptake and Expression in Breast Milk.

The excretion of Ga-DOTA-Octreotate (DOTATATE) and related somatostatin analogues in breast milk has not been demonstrated. We report a case of a 34-year-old woman, 7 months postpartum and breastfeeding, who was referred for DOTATATE imaging after the diagnosis of appendiceal carcinoid and subsequent appendectomy. Prominent breast uptake was noted. A breast milk sample from the patient at 90 minutes postinjection was assayed in a gamma counter and shown to have a concentration of 5.6 Bq/g per MBq administered. The excretion of DOTATATE in breast milk is important to consider when providing radiation safety advice to breastfeeding patients.