Abstract
1069
Objectives: [211At]-astatide has potential as a therapeutic in the management of metastatic thyroid cancer. [211At]-astatide has a different biodistribution and clearance kinetic than radioiodide, and should be independently determined for the accurate estimation of absorbed dose. Whilst SPECT imaging of the [211At]-astatide therapy dose is possible, using a smaller tracer dose of [211At]-astatide, in a manner analogous to a [131I]-iodide tracer dose presents many challenges. Establishing a patient-specific image-based method of determining [211At]-astatide biodistribution would be of great value in dose prescription.
Methods: A simple phantom model was constructed, consisting of individual vials containing 211At, 99mTc and 131I at 0.78, 4.05 and 5.21 mCi respectively, each in a final volume of 250ul. Images were acquired for 10 minutes using a MIlabs uSPECT scanner with a general-purpose mouse collimator. For animal studies, HTH7 anaplastic thyroid cancer cells expressing hNIS as a transgene were grown as subcutaneous xenografts. Animals bearing xenografts were administered 99mTcO4- (5mCi) and [211At]-astatide (1mCi) simultaneously, with SPECT data acquired for 90 minutes. Images were reconstructed using manufacturer-supplied reconstruction algorithm (MiLabs 2.51g) with appropriate background subtraction. Energy windows used were 20% centered at 140keV (99mTc), 25% centered at 84.5 keV (211At) and 20% centered at 364 keV (131I). Images were analyzed using Vivoquant v4.0.
Results: In the phantom studies, 99mTc and 211At were easily resolved based on energy. With both isotope phantoms in the FOV, we were able to resolve each phantom with 99.4% (99mTc) and 98.1% (211At) of the expected counts, based on individual isotope standards. In the dual isotope phantoms, we measured cross-talk between channels of less than 0.4% in each case. The addition of 131I to the FOV resulted in an increase in overall background signal in each channel, and an increased crosstalk between 131I and the other channels (25% in 211At and 11.3% in 99mTc respectively). This is likely due to insufficient collimator performance and resulting down-scattered photons. In vivo imaging following 99mTcO4- and [211At]-astatide co-administration revealed a similar spatial biodistribution, but suggested a different clearance kinetic between the isotopes.
Conclusions: 99mTcO4- and [211At]-astatide may be co-administered and individually resolved in a pre-clinical setting for the evaluation tissue uptake and clearance kinetics. The concurrent use of 131I in this context is not recommended without use of a high-energy collimator of suitable specification. This method will provide a detailed evaluation of 99mTcO4- as a clinical surrogate for image-based [211At]-astatide dose prescription for metastatic thyroid cancer.