Feasibility of MRI-based reference images for image-guided radiotherapy of the pelvis with either cone-beam computed tomography or planar localization images

<div><p></p><p><i><b>Purpose.</b></i> This study introduces methods to conduct image-guided radiotherapy (IGRT) of the pelvis with either cone-beam computed tomography (CBCT) or planar localization images by relying solely on magnetic resonance imaging (MRI)-based reference images.</p><p><i><b>Material and methods.</b></i> Feasibility of MRI-based reference images for IGRT was evaluated against kV CBCT (50 scans, 5 prostate cancer patients) and kV & MV planar (5 & 5 image pairs and patients) localization images by comparing the achieved patient position corrections to those obtained by standard CT-based reference images. T1/T2*-weighted in-phase MRI, Hounsfield unit conversion-based heterogeneous pseudo-CT, and bulk pseudo-CT images were applied for reference against localization CBCTs, and patient position corrections were obtained by automatic image registration. IGRT with planar localization images was performed manually by 10 observers using reference digitally reconstructed radiographs (DRRs) reconstructed from the pseudo-CTs and standard CTs. Quality of pseudo-DRRs against CT-DRRs was evaluated with image similarity metrics.</p><p><i><b>Results.</b></i> The SDs of differences between CBCT-to-MRI and CBCT-to-CT automatic gray-value registrations were ≤ 1.0 mm & ≤ 0.8° and ≤ 2.5 mm & ≤ 3.6° with 10 cm diameter cubic VOI and prostate-shaped VOI, respectively. The corresponding values for reference heterogeneous pseudo-CT were ≤ 1.0 mm & ≤ 0.7° and ≤ 2.2 mm & ≤ 3.3°, respectively. Heterogeneous pseudo-CT was the only type of MRI-based reference image working reliably with automatic bone registration (SDs were ≤ 0.9 mm & ≤ 0.7°). The differences include possible residual errors from planning CT to MRI registration. The image similarity metrics were significantly (p ≤ 0.01) better in agreement between heterogeneous pseudo-DRRs and CT-DRRs than between bulk pseudo-DRRs and CT-DRRs. The SDs of differences in manual registrations (3D) with planar kV and MV localization images were ≤ 1.0 mm and ≤ 1.7 mm, respectively, between heterogeneous pseudo-DRRs and CT-DRRs, and ≤ 1.4 mm and ≤ 2.1 mm between bulk pseudo-DRRs and CT-DRRs.</p><p><i><b>Conclusion.</b></i> This study demonstrated that it is feasible to conduct IGRT of the pelvis with MRI-based reference images.</p></div

In vivo iodide uptake and efficacy.

<p>(<b>a</b>) Tumor uptake of ¹²³I⁻ 0.5 h, 2 h and 13 h after i.v. administration of ¹²³I⁻. The tumors were injected twice with hTERT-viruses 24 h and 48 h prior to radioiodide. 1, Mock-injected tumor; 2, Ad5/3-hTERT-Δgp19K-injected tumor; 3 and 4, Ad5/3-hTERT-hNIS-injected tumors. (<b>b</b>) Ad5/3-hTERT-hNIS significantly prolongs the survival of mice bearing intra pulmonary PC-3MM2 tumors. Mice received 5×10¹⁰ vp of Ad5/3-hTERT-hNIS or diluent intravenously. Next day, the mice were injected intraperitoneally with ¹³¹I⁻. The treatments were repeated once a week for a total of three weeks. Pairwise comparisons with the logrank test were used to compare survival curves, **p<0.01, ***p<0.001 as compared to mock-treated mice. (<b>c</b>) Biodistribution of ¹³¹I⁻ in mice 48 h after the first intravenous Ad5/3-hTERT-hNIS-injection and 24 h after first radioiodide-injection. Bars represent SD.</p

hNIS-expression in prostate cancer cells.

<p>(<b>a</b>) Cells were infected with 10 vp of Ad5/3-hTERT-hNIS (lanes 1 and 3) or control virus Ad5/3-hTERT-Δgp19K (lanes 2 and 4). hNIS-RNA -expression was assayed 24 h (lanes 1 and 2) and 48 h (lanes 3 and 4) later by RT-PCR. ß-actin served as an internal control. (<b>b</b>) ¹²⁵I uptake in prostate cancer cells infected in triplicates with 10 vp of Ad5/3-hTERT-hNIS or Ad5/3-hTERT-Δgp19K. The capability of the cells to concentrate iodide was assessed at 24 h and 48 h after infection. Student's t-test was used for statistical analyses, *p<0.05, **p<0.01, ***p<0.001 as compared to uninfected cells. Bars represent SD.</p

Oncolytic potency of Ad5/3-hTERT-hNIS.

<p>Prostate cancer cells were infected in triplicates with 0.01 to 100 vp/cell and the cell viability was assessed by MTS-assay. Ad5/3Luc1 is a replication-deficient adenovirus. Ad5 WT is the serotype 5 wild-type adenovirus. Ad5/3-hTERT-Δgp19K is similar to Ad5/3-hTERT-hNIS but does not contain hNIS. ***p<0.001 as compared to replication-deficient adenovirus. Bars represent SD.</p

SPECT/CT is sensitive for detecting endogenous NIS- and hNIS-expression.

<p>Mice were given Ad5/3-hTERT-hNIS or diluent and ¹²³I⁻ intravenously for SPECT-scanning. After the SPECT/CT-scan, mice received ¹³¹I⁻ or PBS intraperitoneally. The iodide uptakes were calculated weekly and normalized to the injected dose of ¹²³I⁻. (<b>a</b>) Individual tumor uptake of ¹²³I⁻ (the imaging isotope) in Ad5/3-hTERT-hNIS and Ad5/3-hTERT-hNIS+¹³¹I⁻ -treated mice. All mice received ¹²³I⁻ for evaluation of iodide uptake by SPECT. Mice in the latter group also received ¹³¹I⁻ right after the SPECT imaging for therapeutic purposes. Solid grey line, background level in the absence of Ad5/3-hTERT-hNIS; dotted grey lines, ± SD of background. (<b>b</b>) ¹²³I⁻ uptake in the thyroids. Results are expressed as %ID/mm³×1000 ± SD.</p

Increasing amount of ¹²³I⁻ accumulates in the tumor over time showing progressive virus replication and increasing tumor hNIS-expression.

<p>(<b>a</b>) SPECT/CT image (sagittal section) showing ¹²³I⁻ accumulation into tumor in the lungs of a mouse treated intravenously with Ad5/3-hTERT-hNIS and intraperitoneally with ¹³¹I⁻. (<b>b</b>) Control mouse treated with ¹³¹I⁻ only shows no ¹²³I⁻ -accumulation in the lungs on the course of the treatment. (<b>c</b>) Transverse section of the lungs of the mouse shown in (<b>a</b>) shows accumulation of ¹²³I⁻ into the tumor on the third treatment week. (<b>d</b>) Transverse section of lungs of the mouse shown in (<b>b</b>) shows no accumulation of ¹²³I⁻ into the tumor on the third treatment week. The crossing point of red lines indicates tumor localization.</p

Number of mice positive for uptake of the imaging isotope ¹²³I at the tumor.

<p>The total number of mice analyzed at each time point is given in parentheses. Day indicates the day after first intravenous virus injection. -, not analyzed.</p