In vivo evaluation of tumor uptake and bio-distribution of 99mTc-labeled 1-thio-ß-D-glucose and 5-thio-D-glucose in mice model.

BACKGROUND: To investigate the capacity of 99mTc-labeled 1-thio-ß-D-glucose (1-TG) and 5-thio-D-glucose (5-TG) to act as a marker for glucose consumption in tumor cells in vivo as well as to evaluate the biodistribution of 1-TG and 5-TG. We investigated the biodistribution, including tumor uptake, of 1-TG and 5-TG at various time points after injection (0.5, 2 and 4 h) in human colorectal carcinoma (HCT-116) and human lung adenocarcinoma (A549) xenograft bearing nude mice (N = 4 per tracer and time point). RESULTS: Ex vivo biodistribution studies revealed a moderate uptake with a maximum tumor-to-muscle ratio of 4.22 ± 2.7 and 2.2 ± 1.3 (HCT-116) and of 3.2 ± 1.1 and 4.1 ± 1.3 (A549) for 1-TG and 5-TG, respectively, with a peak at 4 h for 1-TG and 5-TG. Biodistribution revealed a significantly higher uptake compared to blood in kidneys (12.18 ± 8.77 and 12.69 ± 8.93%ID/g at 30 min) and liver (2.6 ± 2.8%ID/g) for 1-TG and in the lung (7.24 ± 4.1%ID/g), liver (6.38 ± 2.94%ID/g), and kidneys (4.71 ± 1.97 and 4.81 ± 1.91%ID/g) for 5-TG. CONCLUSIONS: 1-TG and 5-TG showed an insufficient tumor uptake with a moderate tumor-to-muscle ratio, not reaching the levels of commonly used tracer, for diagnostic use in human colorectal carcinoma and human lung adenocarcinoma xenograft model.

Assessing regional hepatic function changes after hypertrophy induction by radioembolisation: comparison of gadoxetic acid-enhanced MRI and 99mTc-mebrofenin hepatobiliary scintigraphy.

BACKGROUND: To compare Gd-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and 99mTc-labelled mebrofenin hepatobiliary scintigraphy (HBS) as imaging-based liver function tests after unilateral radioembolisation (RE) in patients with primary or secondary liver malignancies. METHODS: Twenty-three patients with primary or secondary liver malignancies who underwent Gd-EOB-DTPA-enhanced MRI within a prospective study (REVoluTion) were evaluated. REVoluTion was a prospective open-label, non-randomised, therapy-optimising study of patients undergoing right-sided or sequential RE for contralateral liver hypertrophy at a single centre in Germany. MRI and hepatobiliary scintigraphy were performed before RE (baseline) and 6 weeks after (follow-up). This exploratory subanalysis compared liver enhancement on hepatobiliary phase MRI normalised to the spleen (liver-to-spleen ratio (LSR)) and the muscle (liver-to-muscle ratio (LMR)) with mebrofenin uptake on HBS for the total liver (TL) and separately for the right (RLL) and left liver lobe (LLL). RESULTS: Mebrofenin uptake at baseline and follow-up each correlated significantly with LSR and LMR on MRI for TL (≤ 0.013) and RLL (≤ 0.049). Regarding the LLL, mebrofenin uptake correlated significantly with LMR (baseline, p = 0.013; follow-up, p = 0.004), whereas with LSR, a borderline significant correlation was only seen at follow-up (p = 0.051; p = 0.046). CONCLUSION: LSRs and LMR correlate with mebrofenin uptake in HBS. This study indicates that Gd-EOB-DTPA-enhanced MRI and 99mTc-labelled mebrofenin HBS may equally be used to assess an increase in contralateral liver lobe function after right-sided RE. RELEVANCE STATEMENT: MRI may be a convenient and reliable method for assessing the future liver remnant facilitating treatment planning and monitoring of patients after RE-induced hypertrophy induction. KEY POINTS: • Both MRI and HBS can assess liver function after RE. • Liver enhancement on MRI correlates with mebrofenin uptake on HBS. • MRI might be a convenient alternative for estimating future liver remnants after hypertrophy induction.

Technical note: Assessment of radiation measurement devices for the detection of [177 Lu]Lu-labeled radiopharmaceuticals containing [177m Lu]Lu-impurities.

BACKGROUND: Nuclear medicine therapies using [177 Lu]Lu-labeled radiopharmaceuticals have increased significantly in recent years. Some of these radiopharmaceuticals contain long-lived impurities of [177m Lu]Lu. Identification of this specific contamination and its quantification is important in different scenarios. PURPOSE: In this study, standard measurement hardware used for handling radioisotopes was evaluated for the measurement of [177m Lu]Lu and [177 Lu]Lu at equilibrium. Device-specific detection limits (LODs) for [177m Lu]Lu were determined according to international standards and then validated. METHODS: The LODs were determined according to the international standard ISO 11929-1 for [177m Lu]Lu for five identical portable contamination monitors (PCMs), a wastewater counter (WWC), and a release counter system (RCS) at different measuring times. Subsequent activity measurements of the defined samples were used to validate the linearity of the measurement instruments down to the LOD for each system. RESULTS: The average LOD across all PCMs was 0.249 ± 0.009 and 0.129 ± 0.005 Bq/cm2 for 10 and 30 s measurements, respectively. The LODs of WWC varied between 3.3 and 4.7 Bq/L for measurement times of 300 s and 0.8-1.3 Bq/L for 3600 s depending on the energy window studied. The LOD of the RCS depended on the container volume and was 0.08 Bq/g for the 50 L container at 60 s measurement. The measurements for all examined devices were linear down to the LOD (correlation coefficient R ≥ 0.96; coefficient of determination R2  ≥ 0.92). CONCLUSIONS: All investigated measuring instruments (PCM, WWC, RCS) were suitable for the determination of [177m Lu]Lu at equilibrium, and their specific LODs were determined. Based on the measurements performed, activity is overestimated; however, this is tolerable because assumptions and measurements in the context of radiation protection should be conservative.

Optimization of SPECT/CT imaging protocols for quantitative and qualitative 99mTc SPECT.

BACKGROUND: The introduction of hybrid SPECT/CT devices enables quantitative imaging in SPECT, providing a methodological setup for quantitation using SPECT tracers comparable to PET/CT. We evaluated a specific quantitative reconstruction algorithm for SPECT data using a 99mTc-filled NEMA phantom. Quantitative and qualitative image parameters were evaluated for different parametrizations of the acquisition and reconstruction protocol to identify an optimized quantitative protocol. RESULTS: The reconstructed activity concentration (ACrec) and the signal-to-noise ratio (SNR) of all examined protocols (n = 16) were significantly affected by the parametrization of the weighting factor k used in scatter correction, the total number of iterations and the sphere volume (all, p < 0.0001). The two examined SPECT acquisition protocols (with 60 or 120 projections) had a minor impact on the ACrec and no significant impact on the SNR. In comparison to the known AC, the use of default scatter correction (k = 0.47) or object-specific scatter correction (k = 0.18) resulted in an underestimation of ACrec in the largest sphere volume (26.5 ml) by - 13.9 kBq/ml (- 16.3%) and - 7.1 kBq/ml (- 8.4%), respectively. An increase in total iterations leads to an increase in estimated AC and a decrease in SNR. The mean difference between ACrec and known AC decreased with an increasing number of total iterations (e.g., for 20 iterations (2 iterations/10 subsets) = - 14.6 kBq/ml (- 17.1%), 240 iterations (24i/10s) = - 8.0 kBq/ml (- 9.4%), p < 0.0001). In parallel, the mean SNR decreased significantly from 2i/10s to 24i/10s by 76% (p < 0.0001). CONCLUSION: Quantitative SPECT imaging is feasible with the used reconstruction algorithm and hybrid SPECT/CT, and its consistent implementation in diagnostics may provide perspectives for quantification in routine clinical practice (e.g., assessment of bone metabolism). When combining quantitative analysis and diagnostic imaging, we recommend using two different reconstruction protocols with task-specific optimized setups (quantitative vs. qualitative reconstruction). Furthermore, individual scatter correction significantly improves both quantitative and qualitative results.

Quantitative imaging of bone remodeling in patients with a unicompartmental joint unloading knee implant (ATLAS Knee System)-effect of metal artifacts on a SPECT-CT-based quantification.

BACKGROUND: SPECT-CT using radiolabeled phosphonates is considered a standard for assessing bone metabolism (e.g., in patients with osteoarthritis of knee joints). However, SPECT can be influenced by metal artifacts in CT caused by endoprostheses affecting attenuation correction. The current study examined the effects of metal artifacts in CT of a specific endoprosthesis design on quantitative hybrid SPECT-CT imaging. The implant was positioned inside a phantom homogenously filled with activity (955 MBq 99mTc). CT imaging was performed for different X-ray tube currents (I = 10, 40, 125 mA) and table pitches (p = 0.562 and 1.375). X-ray tube voltage (U = 120 kVp) and primary collimation (16 × 0.625 mm) were kept constant for all scans. The CT reconstruction was performed with five different reconstruction kernels (slice thickness, 1.25 mm and 3.75 mm, each 512 × 512 matrix). Effects from metal artifacts were analyzed for different CT scans and reconstruction protocols. ROI analysis of CT and SPECT data was performed for two slice positions/volumes representing the typical locations for target structures relative to the prosthesis (e.g., femur and tibia). A reference region (homogenous activity concentration without influence from metal artifacts) was analyzed for comparison. RESULTS: Significant effects caused by CT metal artifacts on attenuation-corrected SPECT were observed for the different slice positions, reconstructed slice thicknesses of CT data, and pitch and CT-reconstruction kernels used (all, p < 0.0001). Based on the optimization, a set of three protocols was identified minimizing the effect of CT metal artifacts on SPECT data. Regarding the reference region, the activity concentration in the anatomically correlated volume was underestimated by 8.9-10.1%. A slight inhomogeneity of the reconstructed activity concentration was detected inside the regions with a median up to 0.81% (p < 0.0001). Using an X-ray tube current of 40 mA showed the best result, balancing quantification and CT exposure. CONCLUSION: The results of this study demonstrate the need for the evaluation of SPECT-CT protocols in prosthesis imaging. Phantom experiments demonstrated the possibility for quantitative SPECT-CT of bone turnover in a specific prosthesis design. Meanwhile, a systematic bias caused by metal implants on quantitative SPECT data has to be considered.

International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres.

PURPOSE: A multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 (90Y)-resin microspheres. METHODS: A steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with 90Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%-79%, no agreement ≤ 49%). RESULTS: Forty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and 99mTc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the 90Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100-120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with 90Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement). CONCLUSION: Practitioners are encouraged to work towards adoption of these recommendations.

The Impact of Unilateral 90Y-radioembolization on Functional Changes in the Contralateral Hepatic Lobe: The Prospective, Open-label RadioEmbolization, Volumetry, and Liver FuncTion Measurements (REVoluTion) Study.

Objectives: To investigate how metabolic function of the contralateral liver lobe is affected by unilateral radioembolization (RE), and to compare the changes in volume and metabolic function. Background: Unilateral RE induces contralateral liver hypertrophy, but it is unknown if metabolic liver function improves in line with volume increases. Methods: This prospective open-label, nonrandomized, therapy-optimizing study included all consecutive patients undergoing right-sided or sequential 90Y-RE for liver malignancies without underlying liver disease or biliary obstruction at a single center in Germany. Magnetic resonance imaging volumetry and hepatobiliary scintigraphy were performed immediately before RE and approximately 6 weeks after RE. Results: Twenty-three patients were evaluated (11 metastatic colorectal cancer, 4 cholangiocellular carcinoma, 3 metastatic breast cancer, 1 each of metastatic neuroendocrine tumor, hepatocellular carcinoma, renal cell carcinoma, oesophageal cancer, pancreatic ductal adenocarcinoma). In the untreated contralateral left liver lobe, mean (SD) metabolic function significantly increased from 1.34 (0.76) %/min/m2 at baseline to 1.56 (0.75) %/min/m2 6 weeks after RE (P = 0.024). The mean (SD) functional volume (liver volume minus tumor volume) of the left liver lobe significantly increased from baseline (407.3 [170.3] mL) to follow-up (499.1 [209.8] mL; P < 0.01), with an equivalent magnitude to the metabolic function increase. There were no reports of grade ≥3 adverse events. Conclusion: This study indicates that unilobar RE produces a significant increase in the metabolic function, and equivalent volume increase, of the contralateral lobe. RE may be a useful option to induce hypertrophy of the future liver remnant before surgical resection of primary or secondary liver malignancies.

Analysis of Bone Scans in Various Tumor Entities Using a Deep-Learning-Based Artificial Neural Network Algorithm-Evaluation of Diagnostic Performance.

The bone scan index (BSI), initially introduced for metastatic prostate cancer, quantifies the osseous tumor load from planar bone scans. Following the basic idea of radiomics, this method incorporates specific deep-learning techniques (artificial neural network) in its development to provide automatic calculation, feature extraction, and diagnostic support. As its performance in tumor entities, not including prostate cancer, remains unclear, our aim was to obtain more data about this aspect. The results of BSI evaluation of bone scans from 951 consecutive patients with different tumors were retrospectively compared to clinical reports (bone metastases, yes/no). Statistical analysis included entity-specific receiver operating characteristics to determine optimized BSI cut-off values. In addition to prostate cancer (cut-off = 0.27%, sensitivity (SN) = 87%, specificity (SP) = 99%), the algorithm used provided comparable results for breast cancer (cut-off 0.18%, SN = 83%, SP = 87%) and colorectal cancer (cut-off = 0.10%, SN = 100%, SP = 90%). Worse performance was observed for lung cancer (cut-off = 0.06%, SN = 63%, SP = 70%) and renal cell carcinoma (cut-off = 0.30%, SN = 75%, SP = 84%). The algorithm did not perform satisfactorily in melanoma (SN = 60%). For most entities, a high negative predictive value (NPV ≥ 87.5%, melanoma 80%) was determined, whereas positive predictive value (PPV) was clinically not applicable. Automatically determined BSI showed good sensitivity and specificity in prostate cancer and various other entities. Particularly, the high NPV encourages applying BSI as a tool for computer-aided diagnostic in various tumor entities.

Iterative CT reconstruction in abdominal low-dose CT used for hybrid SPECT-CT applications: effect on image quality, image noise, detectability, and reader's confidence.

BACKGROUND: Iterative computed tomography (CT) image reconstruction shows high potential for the preservation of image quality in diagnostic CT while reducing patients' exposure; it has become available for low-dose CT (LD-CT) in high-end hybrid imaging systems (e.g. single-photon emission computed tomography [SPECT]-CT). PURPOSE: To examine the effect of an iterative CT reconstruction algorithm on image quality, image noise, detectability, and the reader's confidence for LD-CT data by a subjective assessment. MATERIAL AND METHODS: The LD-CT data were validated for 40 patients examined by an abdominal hybrid SPECT-CT (U = 120 kV, I = 40 mA, pitch = 1.375). LD-CT was reconstructed using either filtered back projection (FBP) or an iterative image reconstruction algorithm (Adaptive Statistical Iterative Reconstruction [ASIR]®) with different parameters (ASIR levels 50% and 100%). The data were validated by two independent blinded readers using a scoring system for image quality, image noise, detectability, and reader confidence, for a predefined set of 16 anatomic substructures. RESULTS: The image quality was significantly improved by iterative reconstruction of the LD-CT data compared with FBP (P ≤ 0.0001). While detectability increased in only 2/16 structures (P ≤ 0.03), the reader's confidence increased significantly due to iterative reconstruction (P ≤ 0.002). Meanwhile, at the ASIR level of 100%, the detectability in bone structure was highly reduced (P = 0.003). CONCLUSION: An ASIR level of 50% represents a good compromise in abdominal LD-CT image reconstruction. The specific ASIR level improved image quality (reduced image noise) and reader confidence, while preserving detectability of bone structure.

The association of intra-therapeutic heterogeneity of somatostatin receptor expression with morphological treatment response in patients undergoing PRRT with [177Lu]-DOTATATE.

AIM: Purpose of this study was to evaluate the association of the spatial heterogeneity (asphericity, ASP) in intra-therapeutic SPECT/ CT imaging of somatostatin receptor (SSR) positive metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) for morphological treatment response to peptide receptor radionuclide therapy (PRRT). Secondly, we correlated ASP derived form a pre-therapeutic OctreoScan (ASP[In]) and an intra-therapeutic [177Lu]-SPECT/CT (ASP[Lu]). MATERIALS AND METHODS: Data from first therapy cycle [177Lu-DOTA0-Tyr3]octreotate ([177Lu]-DOTATATE)-PRRT was retrospectively analyzed in 33 patients (m = 20; w = 13; median age, 72 [46-88] years). The evaluation of response to PRRT was performed according to RECIST 1.1 in responding lesions [RL (SD, PR, CR), n = 104] and non-responding lesions [NRL (PD), n = 27]. The association of SSR tumor heterogeneity with morphological response was evaluated by Kruskal-Wallis test and receiver operating characteristic curve (ROC). The optimal threshold for separation (RL vs. NRL) was calculated using the Youden-index. Relationship between pre- and intra-therapeutic ASP was determined with Spearman's rank correlation coefficient (ρ) and Bland-Altman plots. RESULTS: A total of 131 lesions (liver: n = 59, lymph nodes: n = 48, bone: n = 19, pancreas: n = 5) were analyzed. Lesions with higher ASP values showed a significantly poorer response to PRRT (PD, median: 11.3, IQR: 8.5-15.5; SD, median: 3.4, IQR: 2.1-4.5; PR, median 1.7, IQR: 0.9-2.8; CR, median: 0.5, IQR: 0.0-1.3); Kruskal-Wallis, p<0.001). ROC analyses revealed a significant separation between RL and NRL for ASP after 4 months (AUC 0.85, p<0.001) and after 12 months (AUC 0.94, p<0.001). The optimal threshold for ASP was >5.45% (sensitivity 96% and specificity 82%). The correlation coefficient of pre- and intra-therapeutic ASP revealed ρ = 0.72 (p <0.01). The mean absolute difference between ASP[In] and ASP[Lu] was -0.04 (95% Limits of Agreement, -6.1-6.0). CONCLUSION: Pre- and intra-therapeutic ASP shows a strong correlation and might be an useful tool for therapy monitoring.

Image Quality Assessment for Low-Dose-CT in Hybrid SPECT/CT Imaging.

OBJECTIVES: Low-dose-computed tomography (LD-CT) is used in nuclear medicine hybrid imaging (e.g., SPECT/CT) for attenuation correction of emission data and anatomical correlation of findings. However, there are currently no standards for image quality (e. g., detectability) comparable to those for diagnostic CT. Therefore, the aim of this explorative study was to evaluate retrospective LDCT data in terms of CT image quality and detectability of anatomical structures. METHODS: Two readers blindly scored abdominal LD-CT images (n = 40 patients) in terms of detectability (n = 20 structures/patient), image quality, and readers' confidence in scoring the image quality for a clinically hybrid imaging protocol. Results were analysed by ANOVA to identify factors (e. g., anatomical structures) that influenced performance scores. The inter-rater agreement was evaluated by determining the chance-corrected Cohen's Kappa coefficient. RESULTS: Image noise was acceptable for anatomical correlation in 96.1 % of the readings with an almost perfect inter-rater agreement (KBP = 0.85). A detectability of at least 80 % was observed in 13/20 (KBP ≥ 0.7) and 90 % in 9/20 (KBP ≥ 0.85) of the structures analysed by both readers. The confidence of both readers in scoring image quality was at least sufficient in 98.8 % of the examined patients (KBP = 0.95). CONCLUSION: Although LD-CT protocols commonly used in hybrid imaging have a poor image quality not suitable for primary CT diagnostics, they enable detection of a variety of anatomical structures. LDCT can therefore also be referenced in the associated reports for anatomical correlation of findings from SPECT imaging.

Pre-operative quantification of pulmonary function using hybrid-SPECT/low-dose-CT: A pilot study.

RATIONALE: Pre-operative lobar function is estimated by scintigraphy in patients with pulmonary malignancies and compromised function. This study compared the lobar perfusion determined by scintigraphy (PS) with data from SPECT/low-dose-CT (SPECT/ldCT) analyzed manually and semi-automatic. METHODS: Retrospective analysis on 39 patients (m/f = 25/14; age: 72.5 [22-89] years) with indication for pulmonary perfusion scintigraphy. Imaging was performed using SPECT/ldCT. Data was analyzed manually and by semi-automatic software. Readers' confidence in 3D-segmentation was scored by two independent readers. Interrater agreement was calculated. In addition, Spearman's rank correlation and Wilcoxon's test were used. RESULTS: Results from PS differed significantly from SPECT/ldCT processed manually or semi-automatically in 4/5 lobes (total difference ≤21.6%; rho ≥0.44) and in 3/5 (total difference 21.6%; rho ≥0.37), respectively. Readers' confidence in 3D-segmentation showed a perfect interrater agreement (κ = 0.98). CONCLUSION: Quantification of lobar perfusion by SPECT/ldCT differs significantly from planar scintigraphy (e.g., with potential influence on therapy). The semi-automatic software analysis provides an applicable methodology.

Angiographic Anatomy and Relevance of 3 and 9 O'clock Arteries During Radioembolization.

PURPOSE: 3 and 9 o'clock arteries (3&9As) which supply the common hepatic duct connect hepatic with duodenal/pancreatic territories. The study purpose is to describe the angiographic anatomy of 3&9As and discuss their relevance when performing radioembolization (RE) of liver malignancies. MATERIALS AND METHODS: The anatomy of the 3&9As was systematically investigated by a retrospective analysis of angiograms, technetium Tc-99 m-macroaggregated albumin (MAA) scintigrams, yttrium-90 (Y90) Bremsstrahlung-SPECT/CT datasets, and clinical data of 153 patients who underwent RE between 2010 and 2013. RESULTS: Analysis of preprocedural angiograms identified 3&9As in 36 (24%) of the 153 patients. Following embolization of the gastroduodenal artery, 3&9As were seen in 53 cases (35%). The three most common origins of the 3&9As were the right hepatic artery (n = 14), the cystic artery (n = 11), and S5 and S6 segmental arteries (n = 5 each). Extrahepatic Tc-99 m-MAA deposition in the territory of the 3&9As was significantly more frequent when 3&9As were detectable on preprocedural angiograms (28%visible vs. 11%not visible; p = 0.001) and especially when the 3&9As were not embolized or bridged prior to RE (50%not occluded/bridged vs. 19%occupied/bridged; p = 0.043). The presence of extrahepatic Y90 Bremsstrahlung after RE (n = 17) was attributable to microsphere diversion via the 3&9A territory in four patients and possible diversion via this territory in nine patients. Five of these 13 patients presented with epigastric pain, nausea, or vomiting (CTCAE severity grade ≤ 3) (p = 0.014). CONCLUSION: 3&9As are commonly detectable during evaluation angiography prior to RE, have a variable angioanatomic origin, and should be prophylactically occluded to prevent complications.

Urinary Excretion of Yttrium-90 after Radioembolization with Yttrium-90-Labeled Resin-based Microspheres.

In radioembolic therapy (RET) of hepatic malignancies using yttrium-90 (Y)-labeled resin microspheres, radiation protection is primarily concerned with avoiding contamination by radioactive spheres. However, as Y is bound to the microsphere surface by a potentially reversible ion-exchange process, the aim of this study was to assess the extent of the potential excreted activity in urine. After RET with Y-labeled resin-based microspheres, urinary excretion of free Y was prospectively analyzed in 51 interventions (n = 45 patients) by sampling urine over 48 h (two 24-h intervals) consecutively. The measured urinary concentration of Y, normalized to the administered microsphere activity, was a median of 58.5 kBq L GBq (range = 3.5-590.9 kBq L GBq) and 17.8 kBq L GBq (1.8-58.8 kBq L GBq) for the first and second 24-h periods after administration, respectively (p ≤ 0.0001, F = 28.4, result from ANOVA). The total excreted activity significantly decreased (p ≤ 0.0001) from a median of 72.5 kBq in the first 24-h period to a median of 22.1 kBq in the second 24-h period. Urinary excretion of free Y after resin-based RET occurs for a longer period and at a higher activity excretion than previously published, which has to be considered when patients are either hospitalized or return home after RET. Existing approaches for patient hospitalization, especially in temporary radiation protection areas, justified by the previously reported lower excretion rate, should be re-evaluated, and as a consequence, the current product safety information and handling recommendations for Y-labeled resin-based microspheres may need to be revised.

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

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.

Improvement of image quality and dose management in CT fluoroscopy by iterative 3D image reconstruction.

OBJECTIVES: The objective of this study was to assess the influence of an iterative CT reconstruction algorithm (IA), newly available for CT-fluoroscopy (CTF), on image noise, readers' confidence and effective dose compared to filtered back projection (FBP). METHODS: Data from 165 patients (FBP/IA = 82/74) with CTF in the thorax, abdomen and pelvis were included. Noise was analysed in a large-diameter vessel. The impact of reconstruction and variables (e.g. X-ray tube current I) influencing noise and effective dose were analysed by ANOVA and a pairwise t-test with Bonferroni-Holm correction. Noise and readers' confidence were evaluated by three readers. RESULTS: Noise was significantly influenced by reconstruction, I, body region and circumference (all p ≤ 0.0002). IA reduced the noise significantly compared to FBP (p = 0.02). The effect varied for body regions and circumferences (p ≤ 0.001). The effective dose was influenced by the reconstruction, body region, interventional procedure and I (all p ≤ 0.02). The inter-rater reliability for noise and readers' confidence was good (W ≥ 0.75, p < 0.0001). Noise and readers' confidence were significantly better in AIDR-3D compared to FBP (p ≤ 0.03). Generally, IA yielded a significant reduction of the median effective dose. CONCLUSION: The CTF reconstruction by IA showed a significant reduction in noise and effective dose while readers' confidence increased. KEY POINTS: • CTF is performed for image guidance in interventional radiology. • Patient exposure was estimated from DLP documented by the CT. • Iterative CT reconstruction is appropriate to reduce image noise in CTF. • Using iterative CT reconstruction, the effective dose was significantly reduced in abdominal interventions.

Brain atlas of the Mongolian gerbil (Meriones unguiculatus) in CT/MRI-aided stereotaxic coordinates.

A new stereotaxic brain atlas of the Mongolian gerbil (Meriones unguiculatus), an important animal model in neurosciences, is presented. It combines high-quality histological material for identification of brain structures with reliable stereotaxic coordinates. The atlas consists of high-resolution images of frontal sections alternately stained for cell bodies (Nissl) and myelinated fibers (Gallyas) of 62 rostro-caudal levels at intervals of 350 µm. Brain structures were named according to the Paxinos nomenclature for rodents. The accuracy of the stereotaxic coordinate system was improved substantially by comparing and matching the series of histological sections to in vivo brain images of the gerbil obtained by magnetic resonance imaging (MRI). The skull outlines corresponding to the MR images were acquired using X-ray computerized tomography (CT) and were used to establish the relationship between coordinates of brain structures and skull. Landmarks such as lambda, bregma, ear canals and occipital crest can be used to line up skull and brain in standard atlas coordinates. An easily reproducible protocol allows sectioning of experimental brains in the standard frontal plane of the atlas.

Comparative Evaluation of the Biodistribution Profiles of a Series of Nonpeptidic Neurotensin Receptor-1 Antagonists Reveals a Promising Candidate for Theranostic Applications.

UNLABELLED: Neurotensin receptor-1 (NTR1) is a promising target for diagnostic imaging and targeted radionuclide therapy. The aim of this study was to evaluate the biodistribution profiles of a series of newly developed diarylpyrazole-based NTR1 antagonists regarding their suitability as diagnostic and potentially radiotherapeutic agents. METHODS: 3BP-227, 3BP-228, and 3BP-483 were labeled with (111)In and injected intravenously into NTR1-positive HT29 xenograft-bearing nude mice. At 3, 6, 12, and 24 h after administration, SPECT/CT images were acquired or mice were sacrificed for ex vivo determination of tissue-associated radioactivity. RESULTS: High-contrast tumor visualization in SPECT/CT images was achieved using the 3 compounds of this study. Ex vivo biodistribution studies confirmed a high and persistent tumor uptake, peaking at 6 h after injection for (111)In-3BP-227 (8.4 ± 3.1 percentage injected dose per gram [%ID/g]) and at 3 h after injection for (111)In-3BP-228 (10.2 ± 5.3 %ID/g) and (111)In-3BP-483 (1.9 ± 0.8 %ID/g). Tumor-to-normal-tissue ratios obtained with (111)In-3BP-227 and (111)In-3BP-228 were consistently greater than 1. CONCLUSION: On the basis of the superior biodistribution profile compared with previously reported radiolabeled NTR1 ligands, (111)In-3BP-227 is an ideal candidate for further development as a theranostic tracer.

Pharmacokinetics of 99mTc-MAA- and 99mTc-HSA-Microspheres Used in Preradioembolization Dosimetry: Influence on the Liver-Lung Shunt.

UNLABELLED: Perfusion scintigraphy using (99m)Tc-labeled albumin aggregates is mandatory before hepatic radioembolization with (90)Y-microspheres. As part of a prospective trial, the intrahepatic and intrapulmonary stability of 2 albumin compounds, (99m)Tc-MAA (macroaggregated serum albumin [MAA]) and (99m)Tc-HSA (human serum albumin [HSA]), was assessed. METHODS: In 24 patients with metastatic colorectal cancer, biodistribution (liver, lung) and liver-lung shunt (LLS) of both tracers (12 patients each) were assessed by sequential planar scintigraphy (1, 5, and 24 h after injection). RESULTS: Liver uptake of both albumin compounds decreased differently. Although initial LLSs at 1 h after injection were similar in both groups, MAA-LLS increased significantly from 1 (3.9%) to 5 h (7.7%) and 24 h (9.9%) after injection, respectively. HSA-LLS did not change significantly (1 to 5 h), indicating a steady state of pulmonary and intrahepatic degradation. CONCLUSION: Compared with (99m)Tc-MAA-microspheres, (99m)Tc-HSA-microspheres are likely more resistant to degradation over time, allowing a reliable LLS determination even at later time points.