Quantitative Imaging of Alpha-Emitting Therapeutic Radiopharmaceuticals

Seo, Youngho

doi:10.1007/s13139-019-00589-8

Cited by 31 publications

(17 citation statements)

References 28 publications

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“…Planar scintigraphy images of 212 Pb were obtained by Meredith et al in a clinical study [19] and by Kasten et al in a preclinical study [20]. Surrogate radiopharmaceuticals with more appropriate photon emissions are sometimes used [21], and lead-203 ( 203 Pb) has been investigated as a surrogate isotope for 212 Pb [22,23]. As there are photon emissions in the 212 Pb decay chain that are imageable, we here investigate the possibilities for direct quantitative SPECT imaging of 212 Pb.…”

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confidence: 99%

Quantitative SPECT/CT imaging of lead-212: a phantom study

2022

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Background Lead-212 (212Pb) is a promising radionuclide for targeted therapy, as it decays to α-particle emitter bismuth-212 (212Bi) via β-particle emission. This extends the problematic short half-life of 212Bi. In preparation for upcoming clinical trials with 212Pb, the feasibility of quantitative single photon-emission computed tomography/computed tomography (SPECT/CT) imaging of 212Pb was studied, with the purpose to explore the possibility of individualised patient dosimetric estimation. Results Both acquisition parameters (combining two different energy windows and two different collimators) and iterative reconstruction parameters (varying the iterations x subsets between 10 × 1, 15 × 1, 30 × 1, 30 × 2, 30 × 3, 30 × 4, and 30 × 30) were investigated to evaluate visual quality and quantitative uncertainties based on phantom images. Calibration factors were determined using a homogeneous phantom and were stable when the total activity imaged exceeded 1 MBq for all the imaging protocols studied, but they increased sharply as the activity decayed below 1 MBq. Both a 20% window centred on 239 keV and a 40% window on 79 keV, with dual scatter windows of 5% and 20%, respectively, could be used. Visual quality at the lowest activity concentrations was improved with the High Energy collimator and the 79 keV energy window. Fractional uncertainty in the activity quantitation, including uncertainties from calibration factors and small volume effects, in spheres of 2.6 ml in the NEMA phantom was 16–21% for all protocols with the 30 × 4 filtered reconstruction except the High Energy collimator with the 239 keV energy window. Quantitative analysis was possible both with and without filters, but the visual quality of the images improved with a filter. Conclusions Only minor differences were observed between the imaging protocols which were all determined suitable for quantitative imaging of 212Pb. As uncertainties generally decreased with increasing iterative updates in the reconstruction and recovery curves did not converge with few iterations, a high number of reconstruction updates are recommended for quantitative imaging.

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confidence: 99%

Quantitative SPECT/CT imaging of lead-212: a phantom study

2022

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“…The application of our apparatus could also be extended to imaging of other TAT radionuclides, such as 227 Th, 211 At, or 213 Bi, given their similar gamma-ray emission energies and injected doses [14], although in this article we only explore 225 Ac since it is the most promising one [2].…”

Section: A Relevance Of Our Resultsmentioning

confidence: 99%

“…The dominant gamma-ray emissions of 221 Fr (218 keV) and 213 Bi (440 keV), with branching ratios 11.4% and 25.9%, respectively, can be used to obtain quantitative dose maps using single-photon emission computed tomography (SPECT) [14]. This has been demonstrated with a commercial preclinical micro-SPECT/CT (Vector [15]) with phantoms that required doses two orders of magnitude higher than the toxicity limit in mice [16] and with 24-h exposures.…”

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confidence: 99%

Compton and Proximity Imaging of Ac In Vivo With a CZT Gamma Camera: A Proof of Principle With Simulations

Caravaca¹,

Huh²,

Gullberg³

et al. 2022

IEEE Trans. Radiat. Plasma Med. Sci.

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In vivo imaging of 225 Ac is a major challenge in the development of targeted alpha therapy radiopharmaceuticals due to the extremely low injected doses. In this article, we present the design of a multimodality gamma camera that integrates both proximity and Compton imaging in order to achieve the demanding sensitivities required to image 225 Ac with good image quality. We consider a dual-head camera, each of the heads consisting of two planar cadmium zinc telluride detectors acting as scatterer and absorber for Compton imaging, and with the scatterer practically in contact with the subject to allow for proximity imaging. We optimize the detector's design and characterize the detector's performance using Monte Carlo simulations. We show that Compton imaging can resolve features of up to 1.5 mm for hot-rod phantoms with an activity of 1 µCi, and can reconstruct 3-D images of a mouse injected with 0.5 µCi after a 15-min exposure and with a single bed position, for both 221 Fr and 213 Bi. Proximity imaging is able to resolve two 1 mm-radius sources of less than 0.1 µCi separated by 1 cm and at 1 mm from the detector, as well as it can provide planar images of 221 Fr and 213 Bi biodistributions of the mouse phantom in 5 min.

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“…Adaptations of gamma-ray imaging technologies to αRPT verification are challenging due to the lack of or minimal signal from long-range photons. In vivo assessment of alpha-emitters in tissues must contend with the extremely low administered activities of these procedures, which pose challenges to image quality 8 , 9 . Techniques using surrogate tracers introduce a systematic uncertainty in the radiopharmaceutical kinetics that may dominate the sub-organ effects being examined 6 , 8 .…”

Section: Introductionmentioning

confidence: 99%

“…Without robust in vivo imaging methods, sub-organ alpha-particle effects may be understood through ex vivo biodistribution and dosimetry studies using autoradiography 8 , 10 . Several bioimaging autoradiographs characterized by high resolution and large dynamic range—to extents currently unattainable with in vivo methods—have been developed for preclinical and clinical radiopharmaceutical characterization, including the α-camera 11 , alpha camera 12 , Timepix detector 13 , and iQID (ionizing-radiation quantum imaging detector) camera 14 .…”

Section: Introductionmentioning

confidence: 99%

Small-scale (sub-organ and cellular level) alpha-particle dosimetry methods using an iQID digital autoradiography imaging system

Peter

Sandmaier

Dion

et al. 2022

Sci Rep

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Targeted radiopharmaceutical therapy with alpha-particle emitters (αRPT) is advantageous in cancer treatment because the short range and high local energy deposition of alpha particles enable precise radiation delivery and efficient tumor cell killing. However, these properties create sub-organ dose deposition effects that are not easily characterized by direct gamma-ray imaging (PET or SPECT). We present a computational procedure to determine the spatial distribution of absorbed dose from alpha-emitting radionuclides in tissues using digital autoradiography activity images from an ionizing-radiation quantum imaging detector (iQID). Data from 211At-radioimmunotherapy studies for allogeneic hematopoietic cell transplantation in a canine model were used to develop these methods. Nine healthy canines were treated with 16.9–30.9 MBq 211At/mg monoclonal antibodies (mAb). Lymph node biopsies from early (2–5 h) and late (19–20 h) time points (16 total) were obtained, with 10–20 consecutive 12-µm cryosections extracted from each and imaged with an iQID device. iQID spatial activity images were registered within a 3D volume for dose-point-kernel convolution, producing dose-rate maps. The accumulated absorbed doses for high- and low-rate regions were 9 ± 4 Gy and 1.2 ± 0.8 Gy from separate dose-rate curves, respectively. We further assess uptake uniformity, co-registration with histological pathology, and requisite slice numbers to improve microscale characterization of absorbed dose inhomogeneities in αRPT.

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Quantitative Imaging of Alpha-Emitting Therapeutic Radiopharmaceuticals

Cited by 31 publications

References 28 publications

Quantitative SPECT/CT imaging of lead-212: a phantom study

Quantitative SPECT/CT imaging of lead-212: a phantom study

Compton and Proximity Imaging of Ac In Vivo With a CZT Gamma Camera: A Proof of Principle With Simulations

Small-scale (sub-organ and cellular level) alpha-particle dosimetry methods using an iQID digital autoradiography imaging system

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