Software-assisted dosimetry in peptide receptor radionuclide therapy with ¹⁷⁷Lutetium-DOTATATE for various imaging scenarios

<div><p>In peptide receptor radionuclide therapy (PRRT) of patients with neuroendocrine neoplasias (NENs), intratherapeutic dosimetry is mandatory for organs at risk (e.g. kidneys) and tumours. We evaluated commercial dosimetry software (Dosimetry Toolkit) using varying imaging scenarios, based on planar and/or tomographic data, regarding the differences in calculated organ/tumour doses and the use for clinical routines. A total of 16 consecutive patients with NENs treated by PRRT with ¹⁷⁷Lu-DOTATATE were retrospectively analysed. Single-photon emission computed tomography (SPECT)/low-dose computed tomography (CT) of the thorax and abdomen and whole body (WB) scintigraphy were acquired up to 7 days p.i. (at a maximum of five imaging time points). Different dosimetric scenarios were evaluated: (1) a multi-SPECT-CT scenario using SPECT/CT only; (2) a planar scenario using WB scintigraphy only; and (3) a hybrid scenario using WB scintigraphy in combination with a single SPECT/low-dose CT. Absorbed doses for the kidneys, liver, spleen, lungs, bladder wall and tumours were calculated and compared for the three different scenarios. The mean absorbed dose for the kidneys estimated by the multi-SPECT-CT, the planar and the hybrid scenario was 0.5 ± 0.2 Sv GBq^-1, 0.8 ± 0.4 Sv GBq^-1 and 0.6 ± 0.3 Sv GBq^-1, respectively. The absorbed dose for the residual organs was estimated higher by the planar scenario compared to the multi-SPECT-CT or hybrid scenario. The mean absorbed tumour doses were 2.6 ± 1.5 Gy GBq^-1 for the multi-SPECT-CT, 3.1 ± 2.2 Gy GBq^-1 for the hybrid scenario and 5.3 ± 6.3 Gy GBq^-1 for the planar scenario. SPECT-based dosimetry methods determined significantly lower kidney doses than the WB scintigraphy-based method. Dosimetry based completely on SPECT data is time-consuming and tedious. Approaches combining SPECT/CT and WB scintigraphy have the potential to ensure compromise between accuracy and user-friendliness.</p></div

Residence times for the first therapy cycle (n = 16 patients) estimated by DTK using different imaging scenarios.

<p>Residence times for the first therapy cycle (n = 16 patients) estimated by DTK using different imaging scenarios.</p

ROI/VOI comparison of all three imaging scenarios 24 h p.i. of the same patient.

<p>The delineations of lungs, liver, kidneys, spleen, bladder and tumour (white, in the liver) are shown. (A) 2D presentation (summed coronal slice) of the 3D VOIs of the multi-SPECT-CT scenario. (B) Geometric mean image of the planar scenario with all ROIs. The small elongated delineations (*) next to the ROIs were used for background correction. (C) Geometric mean image of the WB scintigraphies with SPECT/CT based VOIs (hybrid scenario). Here, overlapping regions of interest were automatically removed (#) and corrected.</p

A representative final report of the Dosimetry Toolkit.

<p>(A) Illustration of the serial images of a patient with all regions of interest 4 h, 24 h, 48 h, 72 h and 168h p.i. (B) Normalised time-activity curves for all regions of interest. (C) Calculated residence times of all regions of interest.</p

Flow cytometry analysis of γH2AX-stained DNA double-strand breaks.

<p>Mean γH2AX intensity was assessed in PBMCs immediately, 1 h and 20 h after indicated exposure conditions. (A) Representative overlay histogram of γH2AX-intensity 1 h after indicated exposure (black line) and of corresponding control (gray line). (B) Difference of mean fluorescence intensity (MFI) of γH2AX and IgG-isotype control staining from 16 independent experiments at three different time points after exposure as mean ± SEM (***: P ≤ 0.001; ns: P > 0.05).</p

Dose per injected activity (DpA) and absorbed tumour doses of n = 23 liver tumour lesions of 16 patients for the first therapy cycle.

<p>Dose per injected activity (DpA) and absorbed tumour doses of n = 23 liver tumour lesions of 16 patients for the first therapy cycle.</p

Patient whole body (WB) weight and determined organ masses.

<p>The individual masses estimated with low-dose CT volumetry were used for weight adjustments in OLINDA/EXM software.</p

Dose per injected activity for the first therapy cycle (n = 16 patients), with respect to the different evaluation scenarios.

<p>Dose per injected activity for the first therapy cycle (n = 16 patients), with respect to the different evaluation scenarios.</p

Analysis of DNA Double-Strand Breaks and Cytotoxicity after 7 Tesla Magnetic Resonance Imaging of Isolated Human Lymphocytes

<div><p>The global use of magnetic resonance imaging (MRI) is constantly growing and the field strengths increasing. Yet, only little data about harmful biological effects caused by MRI exposure are available and published research analyzing the impact of MRI on DNA integrity reported controversial results. This in vitro study aimed to investigate the genotoxic and cytotoxic potential of 7 T ultra-high-field MRI on isolated human peripheral blood mononuclear cells. Hence, unstimulated mononuclear blood cells were exposed to 7 T static magnetic field alone or in combination with maximum permissible imaging gradients and radiofrequency pulses as well as to ionizing radiation during computed tomography and γ-ray exposure. DNA double-strand breaks were quantified by flow cytometry and automated microscopy analysis of immunofluorescence stained γH2AX. Cytotoxicity was studied by CellTiter-Blue viability assay and [³H]-thymidine proliferation assay. Exposure of unstimulated mononuclear blood cells to 7 T static magnetic field alone or combined with varying gradient magnetic fields and pulsed radiofrequency fields did not induce DNA double-strand breaks, whereas irradiation with X- and γ-rays led to a dose-dependent induction of γH2AX foci. The viability assay revealed a time- and dose-dependent decrease in metabolic activity only among samples exposed to γ-radiation. Further, there was no evidence for altered proliferation response after cells were exposed to 7 T MRI or low doses of ionizing radiation (≤ 0.2 Gy). These findings confirm the acceptance of MRI as a safe non-invasive diagnostic imaging tool, but whether MRI can induce other types of DNA lesions or DNA double-strand breaks during altered conditions still needs to be investigated.</p></div

Proliferation assay of subsequently PHA-stimulated PBMCs.

<p>[³H]-thymidine incorporation was determined 84 h after indicated exposure conditions. Diagram displays mean ± SEM of 16 independent experiments (***: P ≤ 0.001; ns: P > 0.05).</p