Absorbed fractions in ellipsoidal volumes for β<sup>−</sup>radionuclides employed in internal radiotherapy

Amato, Ernesto; Lizio, Domenico; Baldari, Sergio

doi:10.1088/0031-9155/54/13/013

Cited by 28 publications

(24 citation statements)

References 13 publications

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“…The tumor volumes in the test mice were more ellipsoidal than spherical as illustrated in Figure 4. Amato et al (Amato et al 2009) showed that specific absorbed fractions in spheres and ellipsoids depend on the volume to surface area ratio. The specific absorbed fraction for prolated ellipsoids tend to be smaller than spheres with equivalent volumes.…”

Section: Resultsmentioning

confidence: 99%

Murine-specific Internal Dosimetry for Preclinical Investigations of Imaging and Therapeutic Agents

Bednarz¹,

Grudzinski²,

Marsh³

et al. 2018

Health Physics

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There is a growing need to estimate the absorbed dose to small animals from preclinical investigations involving diagnostic and therapeutic radiopharmaceuticals. This paper introduces a Monte Carlo-based dosimetry platform called RAPID, which is capable of calculating murine-specific three-dimensional (3D) dose distributions. A comparison is performed between absorbed doses calculated with RAPID and absorbed doses calculated in a commonly used reference mouse phantom called MOBY. Four test mice containing different xenografts underwent serial PET/CT imaging using a novel diagnostic therapy (theranostic) agent NM404, which can be labeled with I for imaging or I for therapy. Using the PET/CT data, 3D dose distributions from I-NM404 were calculated in the mice using RAPID. Mean organ doses in these four test mice were compared to mean organ doses derived by using two previously published I S-values datasets in MOBY. In addition, mean tumor doses calculated in RAPID were compared to mean organ doses derived from unit density spheres. Large differences were identified between mean organ doses calculated in the test mice using RAPID and those derived in the MOBY phantom. Mean absorbed dose percent errors in organs ranged between 0.3% and 333%. Overall, mass scaling improved agreement between MOBY phantom calculations and RAPID, where percent errors were all less than 26%, with the exception of the lung in which percent errors reached values of 48%. Percent errors in mean tumor doses in the test mice and unit density spheres were less pronounced but still ranged between 8% and 23%. This work demonstrates the limitations of using pre-computed S-values in computational phantoms to predict organ doses in small animals from theranostic procedures. RAPID can generate accurate 3D dose distributions in small animals and in turn offer much greater insight on the ability of a given theranostic agent to image and treat diseases.

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Section: Resultsmentioning

confidence: 99%

Murine-specific Internal Dosimetry for Preclinical Investigations of Imaging and Therapeutic Agents

Bednarz¹,

Grudzinski²,

Marsh³

et al. 2018

Health Physics

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“…Such low errors are negligible in determining the effectiveness of the therapy. Based on our clinical experience and on the follow-up of the treated patients, [2][3][4] we can affirm that this approach was successfully applied to our population, without needing to differentiate patients on the disease type.…”

mentioning

confidence: 82%

Comment on: “Technical note: Single time point dose estimate for exponential clearance” [Med. Phys. 45(5), 2318‐2324 (2018)]

et al. 2019

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“…Results of the OLINDA2 sphere model were compared with those of an analytical model for determining absorbed fractions and doses in ellipsoids filled with a uniform activity concentration [18–20]. To implement the analytical model, we used the full 152 Tb emission spectrum taken from [21], which includes the β + spectrum extending up to 2.97 MeV, and all monoenergetic electrons and photons.…”

Section: Methodsmentioning

confidence: 99%

Internal radiation dosimetry of a 152Tb-labeled antibody in tumor-bearing mice

et al. 2019

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Background Biodistribution studies based on organ harvesting represent the gold standard pre-clinical technique for dose extrapolations. However, sequential imaging is becoming increasingly popular as it allows the extraction of longitudinal data from single animals, and a direct correlation with deterministic radiation effects. We assessed the feasibility of mouse-specific, microPET-based dosimetry of an antibody fragment labeled with the positron emitter 152 Tb [( T 1/2 = 17.5 h, Eβ + mean = 1140 keV (20.3%)]. Image-based absorbed dose estimates were compared with those obtained from the extrapolation to 152 Tb of a classical biodistribution experiment using the same antibody fragment labeled with 111 In. 152 Tb was produced by proton-induced spallation in a tantalum target, followed by mass separation and cation exchange chromatography. The endosialin-targeting scFv78-Fc fusion protein was conjugated with the chelator p -SCN-Bn-CHX-A”-DTPA, followed by labeling with either 152 Tb or 111 In. Micro-PET images of four immunodeficient female mice bearing RD-ES tumor xenografts were acquired 4, 24, and 48 h after the i.v. injection of 152 Tb-CHX-DTPA-scFv78-Fc. After count/activity camera calibration, time-integrated activity coefficients (TIACs) were obtained for the following compartments: heart, lungs, liver, kidneys, intestines, tumor, and whole body, manually segmented on CT. For comparison, radiation dose estimates of 152 Tb-CHX-DTPA-scFv78-Fc were extrapolated from mice dissected 4, 24, 48, and 96 h after the injection of 111 In-CHX-DTPA-scFv78-Fc (3–5 mice per group). Imaging-derived and biodistribution-derived organ TIACs were used as input in the 25 g mouse model of OLINDA/EXM® 2.0, after appropriate mass rescaling. Tumor absorbed doses were obtained using the OLINDA2 sphere model. Finally, the relative percent difference (RD%) between absorbed doses obtained from imaging and biodistribution were calculated. Results RD% between microPET-based dosimetry and biodistribution-based dose extrapolations were + 12, − 14, and + 17 for the liver, the kidneys, and the tumors, respectively. Compared to biodistribution, the imaging method significantly overestimates the absorbed doses to the heart and the lungs (+ 89 and + 117% dose difference, respectively). Conclusions MicroPET-based dosimetry of 152 Tb is feasible, and the comparison with organ harvesting resulted in acceptable dose discrepancies for body districts that can be segmented on CT. These encouraging results warrant additional validation using radiolabeled biomolecules with a different biodistribution pattern.

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Absorbed fractions in ellipsoidal volumes for β⁻radionuclides employed in internal radiotherapy

Cited by 28 publications

References 13 publications

Murine-specific Internal Dosimetry for Preclinical Investigations of Imaging and Therapeutic Agents

Murine-specific Internal Dosimetry for Preclinical Investigations of Imaging and Therapeutic Agents

Comment on: “Technical note: Single time point dose estimate for exponential clearance” [Med. Phys. 45(5), 2318‐2324 (2018)]

Internal radiation dosimetry of a 152Tb-labeled antibody in tumor-bearing mice

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Absorbed fractions in ellipsoidal volumes for β−radionuclides employed in internal radiotherapy

Cited by 28 publications

References 13 publications

Murine-specific Internal Dosimetry for Preclinical Investigations of Imaging and Therapeutic Agents

Murine-specific Internal Dosimetry for Preclinical Investigations of Imaging and Therapeutic Agents

Comment on: “Technical note: Single time point dose estimate for exponential clearance” [Med. Phys. 45(5), 2318‐2324 (2018)]

Internal radiation dosimetry of a 152Tb-labeled antibody in tumor-bearing mice

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Absorbed fractions in ellipsoidal volumes for β⁻radionuclides employed in internal radiotherapy