Lung Mean Dose Prediction in Transarterial Radioembolization (TARE): Superiority of [166Ho]-Scout Over [99mTc]MAA in a Prospective Cohort Study.

PURPOSE: Radiation pneumonitis is a serious complication of radioembolization. In holmium-166 ([166Ho]) radioembolization, the lung mean dose (LMD) can be estimated (eLMD) using a scout dose with either technetium-99 m-macroaggregated albumin ([99mTc]MAA) or [166Ho]-microspheres. The accuracy of eLMD based on [99mTc]MAA (eLMDMAA) was compared to eLMD based on [166Ho]-scout dose (eLMDHo-scout) in two prospective clinical studies. MATERIALS AND METHODS: Patients were included if they received both scout doses ([99mTc]MAA and [166Ho]-scout), had a posttreatment [166Ho]-SPECT/CT (gold standard) and were scanned on the same hybrid SPECT/CT system. The correlation between eLMDMAA/eLMDHo-scout and LMDHo-treatment was assessed by Spearman's rank correlation coefficient (r). Wilcoxon signed rank test was used to analyze paired data. RESULTS: Thirty-seven patients with unresectable liver metastases were included. During follow-up, none developed symptoms of radiation pneumonitis. Median eLMDMAA (1.53 Gy, range 0.09-21.33 Gy) was significantly higher than median LMDHo-treatment (0.00 Gy, range 0.00-1.20 Gy; p < 0.01). Median eLMDHo-scout (median 0.00 Gy, range 0.00-1.21 Gy) was not significantly different compared to LMDHo-treatment (p > 0.05). In all cases, eLMDMAA was higher than LMDHo-treatment (p < 0.01). While a significant correlation was found between eLMDHo-scout and LMDHo-treatment (r = 0.43, p < 0.01), there was no correlation between eLMDMAA and LMDHo-treatment (r = 0.02, p = 0.90). CONCLUSION: [166Ho]-scout dose is superior in predicting LMD over [99mTc]MAA, in [166Ho]-radioembolization. Consequently, [166Ho]-scout may limit unnecessary patient exclusions and avoid unnecessary therapeutic activity reductions in patients eligible for radioembolization. TRAIL REGISTRATION: NCT01031784, registered December 2009. NCT01612325, registered June 2012.

Deep learning-based attenuation correction method in 99mTc-GSA SPECT/CT hepatic imaging: a phantom study.

This study aimed to evaluate a deep learning-based attenuation correction (AC) method to generate pseudo-computed tomography (CT) images from non-AC single-photon emission computed tomography images (SPECTNC) for AC in 99mTc-galactosyl human albumin diethylenetriamine pentaacetic acid (GSA) scintigraphy and to reduce patient dosage. A cycle-consistent generative network (CycleGAN) model was used to generate pseudo-CT images. The training datasets comprised approximately 850 liver phantom images obtained from SPECTNC and real CT images. The training datasets were then input to CycleGAN, and pseudo-CT images were output. SPECT images with real-time CT attenuation correction (SPECTCTAC) and pseudo-CT attenuation correction (SPECTGAN) were acquired. The difference in liver volume between real CT and pseudo-CT images was evaluated. Total counts and uniformity were then used to evaluate the effects of AC. Additionally, the similarity coefficients of SPECTCTAC and SPECTGAN were assessed using a structural similarity (SSIM) index. The pseudo-CT images produced a lower liver volume than the real CT images. SPECTCTAC exhibited a higher total count than SPECTNC and SPECTGAN, which were approximately 60% and 7% lower, respectively. The uniformities of SPECTCTAC and SPECTGAN were better than those of SPECTNC. The mean SSIM value for SPECTCTAC and SPECTGAN was 0.97. We proposed a deep learning-based AC approach to generate pseudo-CT images from SPECTNC images in 99mTc-GSA scintigraphy. SPECTGAN with AC using pseudo-CT images was similar to SPECTCTAC, demonstrating the possibility of SPECT/CT examination with reduced exposure to radiation.

Measurement of the Tumor-to-Normal Ratio for Radioembolization of Hepatocellular Carcinoma: A Prospective Study Comparing 2-Dimensional Perfusion Angiography, Technetium-99m Macroaggregated Albumin, and Yttrium-90 SPECT/CT.

PURPOSE: To calculate the preradioembolic tumor-to-normal (T:N) ratio in hepatocellular carcinoma (HCC) using 2-dimensional (2D) perfusion angiography and compare it with that calculated using technetium-99m macroaggregated albumin (99mTc MAA) single-photon emission computed tomography (SPECT)/computed tomography (CT). MATERIALS AND METHODS: This prospective single-arm study enrolled 15 participants with HCC who underwent 2D perfusion angiography immediately before the enrollment and with the microcatheter located at the same location as 99mTc MAA injection, after which SPECT/CT was performed. Quantitative digital subtraction angiography was used to calculate the area under the curve for the tumor and normal hepatic parenchyma and subsequently calculate the T:N ratio. The T:N ratio was calculated from the 99mTc MAA SPECT/CT and post-yttrium-90 bremsstrahlung SPECT/CT using dosimetry software. RESULTS: The mean participant age was 64.1 years ± 9.8, and the study included 14 (93%) men and 1 (7%) woman. The mean tumor size was 4.1 cm (SD ± 2.4), and all participants received segmental treatments with glass microspheres. The mean T:N ratio calculated by 99mTc MAA SPECT/CT was 2.28 (SD ± 0.89) vs 2.25 (SD ± 0.99) calculated by 2D perfusion angiography (P = .45). For the 13 participants who underwent selective internal radiation therapy (transarterial radioembolization), there was no significant difference between the T:N ratios calculated by 2D perfusion angiography and post-90Y SPECT/CT (2.25 [SD ± 1.05] vs 1.91 [SD ± 0.39]; P = .12). CONCLUSIONS: The T:N ratio calculated by 2D perfusion angiography correlated well with that calculated by 99mTc MAA SPECT/CT.

Radio-Guided Occult Lesion Localization With 99m Tc for the Localization of Nonpalpable Melanoma and Soft Tissue Sarcoma Lesions: A Feasibility Study.

PURPOSE OF THE REPORT: Localization techniques are needed to facilitate resection of nonpalpable lesions. In this study, the feasibility of radio-guided occult lesion localization (ROLL) with 99m Tc is investigated for the localization of nonpalpable, small, suspicious, or proven melanoma or soft tissue sarcoma lesions at various locations throughout the body. PATIENTS AND METHODS: Patients with nonpalpable, suspicious, or proven melanoma or soft tissue sarcoma lesions were selected for this study. Within 24 hours before surgery, a median dose of 33.92 MBq 99m Tc-labeled human albumin particles ( 99m Tc-NA or 99m Tc-MAA) was injected in the lesion under ultrasound guidance. A hand-held gamma probe was used to detect the radioactive signal and guidance during surgery. RESULTS: In this study, 20 patients with a total of 25 lesions were included and analyzed. The median size of the lesions was 1.8 cm (interquartile range [IQR], 1.8-4.0 cm), of which 44% were intramuscular located and 36% were subcutaneous, and 20% consisted of suspicious lymph nodes, mostly in the lower extremity. At median 4 hours (IQR, 3-6 hours) postinjection, 99m Tc ROLL showed a 100% intraoperative identification rate with proper signal identification with the gamma probe in all patients. With a median surgery time of 76 minutes (IQR, 45-157 minutes), all targeted lesions could be resected without 99m Tc-related complications, resulting in 88% microscopically margin-negative resection. No reoperations were needed for the same lesion. CONCLUSIONS: The 99m Tc ROLL procedure is feasible for the localization and excision of small, nonpalpable melanoma and soft tissue sarcoma lesions at various locations in the body.

Comparison of absorbed doses to the tumoral and non-tumoral liver in HCC patients undergoing 99mTc-MAA and 90Y-microspheres radioembolization.

PURPOSE: This study aimed to determine the absorbed doses in the tumoral-liver and non-tumoral liver of hepatocellular carcinoma (HCC) patients undergoing radioembolization with Yttrium-90 (90Y) resin microspheres, and compared with those derived from 99mTc-MAA using the partition model. METHODS: A total of 42 HCC patients (28 males and 14 females, mean age 65 ± 11.51 years) who received 45 treatment sessions with 90Y-microspheres between 2016 and 2021 were included. Pre-treatment 99mTc-MAA and post-treatment 90Y-bremsstrahlung SPECT/CT were acquired for each patient. Semi-automated segmentation of regions of interest (ROIs) was performed using MIM Encore software to determine the tumor-liver ratio (TLR) encompassing the liver volume, tumoral-liver, and lungs, and verified by both nuclear medicine physician and interventional radiologist. A partition dosimetry model was used to estimate the administered activity of 90Y-microspheres and the absorbed doses to the tumoral-liver and non-tumoral liver. The student's paired t test and Bland-Altman plot were used for the statistical analysis. RESULTS: The mean TLR values obtained from 99mTc-MAA SPECT/CT and 90Y-bremsstrahlung SPECT/CT were 4.78 ± 3.51 and 2.73 ± 1.18, respectively. The mean planning administered activity of 90Y-microspheres based on 99mTc-MAA SPECT/CT was 1.56 ± 0.80 GBq, while the implanted administered activity was 2.53 ± 1.23 GBq (p value < 0.001). The mean absorbed doses in the tumoral-liver estimated from 99mTc-MAA and 90Y-bremsstrahlung SPECT/CT were 127.44 ± 4.36 Gy and 135.98 ± 6.30 Gy, respectively. The corresponding mean absorbed doses in the non-tumoral liver were 34.61 ± 13.93 Gy and 55.04 ± 16.36 Gy. CONCLUSION: This study provides evidence that the administered activity of 90Y-microspheres, as estimated from 90Y-bremsstrahlung SPECT/CT, was significantly higher than that estimated from 99mTc-MAA SPECT/CT resulted in increased absorbed doses in both the tumoral-liver and non-tumoral liver. However, 99mTc-MAA SPECT/CT remains a valuable planning tool for predicting the distribution of 90Y-microspheres in liver cancer treatment.

Correlation between pulmonary embolism and blood cell count changes.

Pulmonary embolism is one of the acute diseases of the respiratory system. This study investigates changes in red blood cell counts in pulmonary embolisms confirmed by scintigraphy. Counting red blood cells is essential in diseases, especially pulmonary embolism, because of the vital role of these cells.  In this study, 25 patients with pulmonary embolism were selected. A group of 25 healthy volunteers was also considered as a control. At zero, 30, 60 minutes, 24, 48, and 72 hours, blood samples were taken from both control and patient groups, and red blood cells were counted according to the standard method. After extracting technetium-99m from the molybdenum generator, this substance was added to the MAA drug kit under particular conditions. After preparation, radiopharmaceutical 99mTC-MAA with 1.5 millicuries was injected intravenously into both groups. In this study, a significant increase in the red blood cell count of the patient group was observed on the first and second days of the disease. On the third day, this count returned to normal. These changes indicate the functioning of the body's defense system and a response to reduce the complications caused by pulmonary embolism. Therefore, paying more attention to counting red blood cells in pulmonary embolism, along with other care, is recommended due to their particular function.

Radioactive nanosized colloids and indocyanine green identify the same sentinel lymph nodes in oral squamous cell carcinoma.

PURPOSE: Near-infrared fluorescence imaging using indocyanine green (ICG) combined with radioactive markers has the potential to improve sentinel lymph-node (SLN) mapping in oral squamous cell carcinoma (OSCC). This study aimed to evaluate the ability of 99mTc and ICG in identifying the sentinel lymph nodes in patients with early stage OSCC. METHODS: Data were collected prospectively, and a retrospective analysis of 15 patients with early stage OSCC and a cN0 neck was performed. All patients received peritumoral injection of 99mTc the day before surgery and ICG was administered intraoperatively. Intentionally, the application of the two different tracers were done by two different physicians with varying degrees of experience. The number of identified lymph nodes positive for 99mTc and ICG, the overlap or possible discrepancies of both methods, and the time until fluorescence signals of ICG were detected were noted. RESULTS: In all patients, a 100% agreement in sentinel lymph-node identification was achieved, regardless of both the exact location of the peritumoral injection and the experience of the injecting surgeon. Time until ICG accumulation in the sentinel lymph node was consistently found to be between 1 and 3 min. CONCLUSION: ICG constitutes a viable and useful addition to 99mTc for intraoperative sentinel lymph-node detection in this study.

Direct comparison and reproducibility of two segmentation methods for multicompartment dosimetry: round robin study on radioembolization treatment planning in hepatocellular carcinoma.

PURPOSE: Investigate reproducibility of two segmentation methods for multicompartment dosimetry, including normal tissue absorbed dose (NTAD) and tumour absorbed dose (TAD), in hepatocellular carcinoma patients treated with yttrium-90 (90Y) glass microspheres. METHODS: TARGET was a retrospective investigation in 209 patients with < 10 tumours per lobe and at least one tumour ≥ 3 cm ± portal vein thrombosis. Dosimetry was compared using two distinct segmentation methods: anatomic (CT/MRI-based) and count threshold-based on pre-procedural 99mTc-MAA SPECT. In a round robin substudy in 20 patients with ≤ 5 unilobar tumours, the inter-observer reproducibility of eight reviewers was evaluated by computing reproducibility coefficient (RDC) of volume and absorbed dose for whole liver, whole liver normal tissue, perfused normal tissue, perfused liver, total perfused tumour, and target lesion. Intra-observer reproducibility was based on second assessments in 10 patients ≥ 2 weeks later. RESULTS: 99mTc-MAA segmentation calculated higher absorbed doses compared to anatomic segmentation (n = 209), 43.9% higher for TAD (95% limits of agreement [LoA]: - 49.0%, 306.2%) and 21.3% for NTAD (95% LoA: - 67.6%, 354.0%). For the round robin substudy (n = 20), inter-observer reproducibility was better for anatomic (RDC range: 1.17 to 3.53) than 99mTc-MAA SPECT segmentation (1.29 to 7.00) and similar between anatomic imaging modalities (CT: 1.09 to 3.56; MRI: 1.24 to 3.50). Inter-observer reproducibility was better for larger volumes. Perfused normal tissue volume RDC was 1.95 by anatomic and 3.19 by 99mTc-MAA SPECT, with corresponding absorbed dose RDC 1.46 and 1.75. Total perfused tumour volume RDC was higher, 2.92 for anatomic and 7.0 by 99mTc-MAA SPECT with corresponding absorbed dose RDC of 1.84 and 2.78. Intra-observer variability was lower for perfused NTAD (range: 14.3 to 19.7 Gy) than total perfused TAD (range: 42.8 to 121.4 Gy). CONCLUSION: Anatomic segmentation-based dosimetry, versus 99mTc-MAA segmentation, results in lower absorbed doses with superior reproducibility. Higher volume compartments, such as normal tissue versus tumour, exhibit improved reproducibility. TRIAL REGISTRATION: NCT03295006.

99mTc-macroaggregated albumin SPECT/CT predictive dosimetry and dose-response relationship in uveal melanoma liver metastases treated with first-line selective internal radiation therapy.

First-line selective internal radiation therapy (SIRT) showed promising outcomes in patients with uveal melanoma liver metastases (UMLM). Patient survival depends on liver's disease control. SIRT planning is essential and little is known about dosimetry. We investigated whether 99mTc-MAA-SPECT/CT dosimetry could predict absorbed doses (AD) evaluated on 90Y-PET/CT and assess the dose-response relationship in UMLM patients treated with first-line SIRT. This IRB-approved, single-center, retrospective analysis (prospectively collected cohort) included 12 patients (median age 63y, range 43-82). Patients underwent MRI/CT, 18F-FDG-PET/CT before and 3-6 months post-SIRT, and 90Y-PET/CT immediately post-SIRT. Thirty-two target lesions were included. AD estimates in tumor and non-tumor liver were obtained from 99mTc-MAA-SPECT/CT and post-SIRT 90Y-PET/CT, and assessed with Lin's concordance correlation coefficients (ρc and Cb), Pearson's coefficient correlation (ρ), and Bland-Altman analyses (mean difference ± standard deviation; 95% limits-of-agreement (LOA)). Influence of tumor characteristics and microsphere type on AD was analyzed. Tumor response was assessed according to size-based, enhancement-based and metabolic response criteria. Mean target lesion AD was 349 Gy (range 46-1586 Gy). Concordance between 99mTc-MAA-SPECT/CT and 90Y-PET/CT tumor dosimetry improved upon dose correction for the recovery coefficient (RC) (ρ = 0.725, ρc = 0.703, Cb = 0.969) with good agreement (mean difference: - 4.93 ± 218.3 Gy, 95%LOA: - 432.8-422.9). Without RC correction, concordance was better for resin microspheres (ρ = 0.85, ρc = 0.998, Cb = 0.849) and agreement was very good between predictive 99mTc-MAA-SPECT/CT and 90Y-PET/CT dosimetry (mean difference: - 4.05 ± 55.9 Gy; 95%LOA: - 113.7-105.6). After RC correction, 99mTc-MAA-SPECT/CT dosimetry overestimated AD (- 70.9 ± 158.9 Gy; 95%LOA: - 382.3-240.6). For glass microspheres, concordance markedly improved with RC correction (ρ = 0.790, ρc = 0.713, Cb = 0.903 vs without correction: ρ = 0.395, ρc = 0.244, Cb = 0.617) and 99mTc-MAA-SPECT/CT dosimetry underestimated AD (148.9 ± 267.5 Gy; 95%LOA: - 375.4-673.2). For non-tumor liver, concordance was good between 99mTc-MAA-SPECT/CT and 90Y-PET/CT dosimetry (ρ = 0.942, ρc = 0.852, Cb = 0.904). 99mTc-MAA-SPECT/CT slightly overestimated liver AD for resin (3.4 ± 3.4 Gy) and glass (11.5 ± 13.9 Gy) microspheres. Tumor AD was not correlated with baseline or post-SIRT lesion characteristics and no dose-response threshold could be identified. 99mTc-MAA-SPECT/CT dosimetry provides good estimates of AD to tumor and non-tumor liver in UMLM patients treated with first-line SIRT.

Predictive Partition Dosimetry and Outcomes after Yttrium-90 Resin Microsphere Radioembolization of Colorectal Cancer Metastatic to the Liver: A Retrospective Analysis.

PURPOSE: To characterize estimated absorbed tumor dose (ADT), objective response (OR), and estimated target dose of liver metastatic colorectal cancer (mCRC) after resin microsphere yttrium-90 (90Y) radioembolization using partition dosimetry. MATERIALS AND METHODS: In this retrospective, single-center study, multicompartment dosimetry of index tumors undergoing 90Y radioembolization from October 2013 to July 2022 was performed using MIM SurePlan and pretreatment technetium-99m macroaggregated albumin infusion data. Thirty-eight patients with mCRC underwent treatments for 59 index tumors. Patients were imaged every 2-3 months after treatment and then every 3-6 months after disease control to determine the best response per Response Evaluation Criteria in Solid Tumors 1.1. Responses were categorized as OR or nonresponse (NR). A Cox proportional hazards model evaluated the probability of tumor OR and local progression-free survival (LPFS) based on ADT. RESULTS: Patients had a median follow-up of 116 days (interquartile range [IQR], 69-231 days). The ADT was higher for OR patients than for NR patients (median, 130.8 [IQR, 85.6-239.0] vs 40.6 [IQR, 26.0-66.3] Gy; P < .001). A greater percentage of OR than NR patients were treated with activities calculated by partition modeling (54% vs 12%; P = .005). Only ADT predicted response (P = .032). At 6 months, an ADT of 120 Gy predicted a 55% (95% CI, 0.0%-89%) probability of OR. Only ADT (P = .010) and female sex (P = .014) predicted LPFS. At 1 year, an ADT of 120 Gy predicted a 70% (95% CI, 35%-100%) probability of LPFS. CONCLUSIONS: Tumor dose was the strongest predictor of OR for mCRC. Administration of an estimated 120 Gy to mCRC predicted 55% OR with 90Y resin microspheres at 6 months.

Predicting the net administered activity in 90 Y-radioembolization patients from post-procedure 90 Y-SPECT/CT.

BACKGROUND: The calculation of the net administered activity (Aadmin ) in patients undergoing 90 Y-radioembolization is essential for dosimetry and radiation safety, yet current methods for measuring residual 90 Y activity are often associated with high uncertainty. Therefore, an accurate, robust, and clinically viable method for the determination of Aadmin across approved 90 Y microsphere devices is desirable. PURPOSE: We report on a novel method to determine Aadmin by leveraging the quantitative capabilities of SPECT/CT to measure 90 Y-emission in vivo from patients following 90 Y-radioembolization with glass or resin microspheres. METHODS: 90 Y-SPECT/CT attenuation-corrected count data from 147 sequential 90 Y-radioembolization patients was used for this analysis. Aadmin was calculated as part of routine clinical practice via the exposure rate differences between the initial 90 Y-vial and the 90 Y-residual jar. This served as our gold standard measure of Aadmin . Patient data for each microsphere device were separated into training and testing cohorts to first develop regression models and then to independently assess model performance. The training cohorts were divided into four groups: first, based on the microsphere device (glass or resin), and second, based on the SPECT volume used to calculate counts (the full SPECT field of view (FOV) or liver only (VOIliver )). Univariate linear regression models were generated for each group to predict Aadmin based on 90 Y-SPECT data from the training cohorts. Leave-one-out cross validation was implemented to estimate variability in model parameters. To assess performance, linear models derived from the training cohort were applied to 90 Y-SPECT data from the testing cohort. A comparison of the models between microspheres devices was also performed. RESULTS: Linear models derived from the glass and resin training cohorts demonstrated a strong, positive correlation between 90 Y-SPECT image counts and Aadmin for VOIliver and FOV with R2  > 0.98 in all cases. In the glass training cohort, model accuracy (100%-absolute mean prediction error) and precision (95% prediction intervals of mean prediction error) were 99.0% and 15.4% for the VOIliver and 99.7% and 17.5% for the FOV models, respectively. In the resin training cohort, the corresponding values were 98.6% and 16.7% for VOIliver and > 99.9% and 11.4% for the FOV models, respectively. The application of these linear models to 90 Y-SPECT data from the testing cohort showed Aadmin prediction errors to have high accuracy and precision for both microsphere devices. For the glass testing cohort, accuracy (precision) was 96.9% (19.6%) and 98.8% (21.1%) for the VOIliver and FOV models, respectively. The corresponding values for the resin training cohort were 97.3% (26.2%) and 98.5% (25.7%) for the VOIliver and FOV models, respectively. The slope of the linear models between the two microsphere devices was observed to be significantly different with resin microspheres generating 48%-49% more SPECT counts for equivalent 90 Y activity based on each device manufacturer's activity calibration process. CONCLUSION: 90 Y-SPECT image counts can reliably predict (accuracy > 95% and precision < 18%) Aadmin after 90 Y-radioembolization, with performance characteristics essentially equivalent for both glass and resin microspheres. There is a clear indication that activity calibrations are fundamentally different between the two microsphere devices.

Synchronous Treatment of Breast Cancer Hepatic Metastases by Transarterial Radioembolization and Radiofrequency Thermoablation: A Case Report.

ABSTRACT: In a 51-year-old woman affected by breast cancer, hepatic recurrence of disease was managed by concurrent 90 Y-labeled glass microsphere embolization (transarterial radioembolization) and radiofrequency thermoablation. Intention-to-treat target, candidate to radioembolization, was in the IV hepatic segment; another lesion, managed with radiofrequency thermoablation, was in the VI-VII hepatic segment. Concomitant correction of a duodenocephalopancreatic shunting was performed as well. Thermoablation did not interfere with distribution of 99m Tc-macroaggregated albumin and 90 Y-labeled microspheres to the target and healthy liver. At our knowledge, this is the first report that combines 2 locoregional procedures in different hepatic segments on the same day.

[Impact of Residual Radioactivity Rate of 99mTc-macro Aggregated Albumin (MAA) in Syringes and Administration Routes with a Focus on Pediatric Nuclear Medicine Examinations].

PURPOSE: The purpose of this study was to evaluate the residual radioactivity in the syringe and route of administration of a low fluid volume 99mTc-macro aggregated albumin (MAA) intended for pediatric nuclear medicine examinations. METHOD: We evaluated the residual characteristics, as the effect of elapsed time from drawing up of radiopharmaceuticals to plastic syringe to administration, and the effect of volume of 99mTcO4- solution to be labeled, the effect of rinsed times of plastic syringe, effect of dose of calculated by consensus guidelines for pediatric nuclear medicine and residual location in injection sets with 99mTc-MAA. Residual radioactivity was measured using planar images obtained by the gamma camera. RESULTS: Residual radioactivity rate of 99mTc-MAA, 99mTc-MAG3, 123I-IMP showed 41.3±1.6%, 14.4±0.6%, 14.6±2.0%, respectively. 99mTc-MAA clearly showed a higher residual rate. Residual radioactivity rate increased with the extension of the elapsed time, and reached a high value of 41.3% in 30 minutes. Residual radioactivity rate was dependent on the different volume of 99mTcO4- to be labeled (4.0 ml and 8.0 ml). Residual radioactivity rate did not change when the number of rinsed was more than one. Residual rate was around 40% at all doses of calculated by consensus guidelines for pediatric nuclear medicine. CONCLUSION: 99mTc-MAA showed the highest residual radioactivity rate among radiopharmaceuticals used in pediatric nuclear medicine examinations. The factor that most affected the residual radioactivity rate of 99mTc-MAA was the elapsed time from draw up to the plastic syringe to administration.

A hybrid radioactive and fluorescence approach is more than the sum of its parts; outcome of a phase II randomized sentinel node trial in prostate cancer patients.

OBJECTIVE: To determine the diagnostic accuracy of the hybrid tracer indocyanine green (ICG)-Technetium-99 m(99mTc)-nanocolloid compared to sequential tracers of 99mTc-nanocolloid and free-ICG in detecting tumor-positive lymph nodes (LN) during primary surgery in prostate cancer (PCa) patients. INTRODUCTION: Image-guided surgery strategies can help visualize individual lymphatic drainage patterns and sentinel lymph nodes (SLNs) in PCa patients. For lymphatic mapping radioactive, fluorescent and hybrid tracers are being clinically exploited. In this prospective randomized phase II trial, we made a head-to-head comparison between ICG-99mTc-nanocolloid (hybrid group) and 99mTc-nanocolloid and subsequent free-ICG injection (sequential group). METHODS: PCa patients with a >5% risk of lymphatic involvement according to the 2012 Briganti nomogram and planned for prostatectomy were included and randomized (1:1) between ultrasound-guided intraprostatic tracer administration of ICG-99mTc-nanocolloid (n = 69) or 99mTc-nanocolloid (n = 69) 5 h before surgery. Preoperative lymphoscintigraphy and SPECT/CT were performed to define the locations of the SLNs. Additionally, all participants in the sequential group received an injection of free-ICG at time of surgery. Subsequently, all (S)LNs were dissected using fluorescence guidance followed by an extended pelvic lymph node dissection (ePLND). The primary outcome was the total number of surgically removed (S)LNs and tumor-positive (S)LNs. RESULTS: The total number of surgically removed (S)LN packages was 701 and 733 in the hybrid and sequential groups, respectively (p = 0.727). The total number of fluorescent LNs retrieved was 310 and 665 nodes in the hybrid and sequential groups, respectively (p < 0.001). However, no statistically significant difference was observed in the corresponding number of tumor-positive nodes among the groups (44 vs. 33; p = 0.470). Consequently, the rate of tumor-positive fluorescent LNs was higher in the hybrid group (7.4%) compared to the sequential group (2.6%; p = 0.002), indicating an enhanced positive predictive value for the hybrid approach. There was no difference in complications within 90 days after surgery (p = 0.78). CONCLUSIONS: The hybrid tracer ICG-99mTc-nanocolloid improved the positive predictive value for tumor-bearing LNs while minimizing the number of fluorescent nodes compared to the sequential tracer approach. Consequently, the hybrid tracer ICG-99mTc-nanocolloid enables the most reliable and minimal invasive method for LN staging in PCa patients.

Comparison of two hybrid sentinel node tracers: indocyanine green (ICG)-99mTc-nanocolloid vs. ICG-99mTc-nanoscan from a nuclear medicine and surgical perspective.

BACKGROUND: Lymph node (LN) metastasis is a relevant predictor for survival in patients with a.o. penile cancer (PeCa), malignant melanoma. The sentinel node (SN) procedure comprises targeted resection of the first tumour-draining SNs. Here, the hybrid tracer indocyanine green (ICG)-99mTc-nanocolloid has been used for several years to combine optical and nuclear detection. Recently, the resource of the nanocolloid precursor stopped production and the precursor was replaced by a different but chemically comparable colloid, nanoscan. Our aim was to study the performance of ICG-99mTc-nanoscan compared to ICG-99mTc-nanocolloid from a nuclear and surgical perspective. METHODS: Twenty-four patients with either PeCa or head-and-neck (H&N) melanoma and scheduled for a SN procedure were included. The initial group (n = 11) received ICG-99mTc-nanocolloid until no longer available; the second group (n = 13) received ICG-99mTc-nanoscan. Tracer uptake was assessed on lymphoscintigraphy and single-photon emission (SPECT). Intraoperatively, SNs were identified using gamma tracing and fluorescence imaging. Ex vivo (back-table) measurements were conducted to quantify the fluorescence emissions. Chemical analysis was performed to compare the ICG assembly on both precursors. RESULTS: The mean tracer uptake in the SNs was similar for ICG-99mTc-nanocolloid (2.2 ± 4.3%ID) and ICG-99mTc-nanoscan (1.8 ± 2.6%ID; p = 0.68). 3 SNs (interquartile range (IQR) 3-4) were detected on lymphoscintigraphy in PeCa patients receiving ICG-99mTc-nanoscan compared to 2 SNs (IQR 2-3) in PeCa patients receiving ICG-99mTc-nanocolloid (p = 0.045), no differences were observed in H&N patients. Back-table measurements of resected SNs revealed a lower total fluorescence intensity in the ICG-99mTc-nanoscan group (24*109 arbitrary units (A.U) IQR 1.6*109-14*109 in the ICG-99mTc-nanocolloid group versus 4.6*109 A.U. IQR 2.4*109-42*109 in the ICG-99mTc-nanoscan group, p = 0.0054). This was consistent with a larger degree of "stacked" ICG observed in the nanoscan formulation. No tracer-related adverse events were reported. CONCLUSIONS: Based on this retrospective analysis, we can conclude that ICG-99mTc-nanoscan has similar capacity for SN identification as ICG-99mTc-nanocolloid and can safely be implemented in SN procedures.

Sentinel node identification in laryngeal and pharyngeal carcinoma after flexible endoscopy-guided tracer injection under topical anesthesia: A feasibility study.

BACKGROUND: The aim of this study was to investigate the feasibility of flexible endoscopy-guided tracer injection for sentinel lymph node (SLN) identification in patients with laryngeal and pharyngeal carcinoma. METHODS: Sixteen cT1-4N0-2M0 patients with laryngeal or pharyngeal carcinoma underwent intra- and peritumoral [99m Tc]Tc-nanocolloid injections after topical anesthesia under endoscopic guidance. SPECT-CT scans were performed at two time points. RESULTS: Tracer injection and visualization of SLNs was successful in 15/16 (94%) patients. Median number of tracer injections was 1 intratumoral and 3 peritumoral. The median duration of the endoscopic procedure including tracer injection after biopsy taking was 7 min (range 4-16 min). A total of 28 SLNs were identified which were all visualized on the early and late SPECT-CT. Most SLNs were visualized in neck levels II and III. CONCLUSIONS: Flexible endoscopy-guided tracer injection for SLN identification is a feasible and fast procedure in laryngeal and pharyngeal carcinoma patients.

SPECT and CT misregistration reduction in [99mTc]Tc-MAA SPECT/CT for precision liver radioembolization treatment planning.

PURPOSE: Respiration and body movement induce misregistration between static [99mTc]Tc-MAA SPECT and CT, causing lung shunting fraction (LSF) and tumor-to-normal liver ratio (TNR) errors for 90Y radioembolization planning. We aim to alleviate the misregistration between [99mTc]Tc-MAA SPECT and CT using two registration schemes on simulation and clinical data. METHODS: In the simulation study, 70 XCAT phantoms were modeled. The SIMIND Monte Carlo program and OS-EM algorithm were used for projection generation and reconstruction, respectively. Low-dose CT (LDCT) at end-inspiration was simulated for attenuation correction (AC), lungs and liver segmentation, while contrast-enhanced CT (CECT) was simulated for tumor and perfused liver segmentation. In the clinical study, 16 patient data including [99mTc]Tc-MAA SPECT/LDCT and CECT with observed SPECT and CT mismatch were analyzed. Two liver-based registration schemes were studied: SPECT registered to LDCT/CECT and vice versa. Mean count density (MCD) of different volumes-of-interest (VOIs), normalized mutual information (NMI), LSF, TNR, and maximum injected activity (MIA) based on the partition model before and after registration were compared. Wilcoxon signed-rank test was performed. RESULTS: In the simulation study, compared to before registration, registrations significantly reduced estimation errors of MCD of all VOIs, LSF (Scheme 1: - 100.28%, Scheme 2: - 101.59%), and TNR (Scheme 1: - 7.00%, Scheme 2: - 5.67%), as well as MIA (Scheme 1: - 3.22%, Scheme 2: - 2.40%). In the clinical study, Scheme 1 reduced 33.68% LSF and increased 14.75% TNR, while Scheme 2 reduced 38.88% LSF and increased 6.28% TNR compared to before registration. One patient may change from 90Y radioembolization untreatable to treatable and other patients may change the MIA up to 25% after registration. NMI between SPECT and CT was significantly increased after registrations in both studies. CONCLUSION: Registration between static [99mTc]Tc-MAA SPECT and corresponding CTs is feasible to reduce their spatial mismatch and improve dosimetric estimation. The improvement of LSF is larger than TNR. Our method can potentially improve patient selection and personalized treatment planning for liver radioembolization.

An In-House 3D Voxel Dosimetric Tool to Compare Predictive and Post- Treatment Dosimetry in 90Y Radioembolization: A Proof of Concept.

AIM: The aim of this study was to implement an in-house dosimetric tool to assess tumour- absorbed doses in pre and post-dosimetry for 90Y radioembolization with resin spheres. MATERIALS AND METHODS: To perform dosimetric calculations we set up a dosimetric procedure and developed homemade software to calculate tumour absorbed dose and dose volume histograms (DVHs). The method is based on a simplified voxel dosimetry for an estimated 3D absorbed dose and it can be applied to both 99mTc-MAA SPECT/CT and 90Y PET/CT acquisitions for pre and post-dosimetry. We tested the software performance in a retrospective study using the data of 22 patients with hepatocellular carcinoma who underwent radioembolization with 90Y resin spheres in the period 2016-2021. The software calculates tumour doses (mean, minimum and maximum doses) from voxel counts and dose-volume histograms (DVH_spect, DVH_pet) for both 99mTc-MAA SPECT/CT and 90Y PET/CT imaging. DVH_spect and DVH_pet data were analyzed and compared with the aim to assess an agreement between them. Concordance between dosimetric data were evaluated with the Wilcoxon Signed Ranked test, descriptive statistical analysis and Pearson correlation coefficient. RESULTS: The mean administrated activity was 1313 MBq (range 444 MBq - 2200 MBq). Tumour volumes ranged from 75 mL to 1012 mL. The mean absorbed dose for tumour volume was 161 ± 66 Gy (Dm_spect) and 173 ± 79 Gy (Dm_pet). From Wilcoxon Signed Rank Test the differences between the dosimetric data extrapolated from DVH_spect and DVH_pet results were not significant with α = 0.05 (two-sided test). A good linear correlation was found between 99mTc-MAA and 90Y dosimetric data (Pearson correlation coefficient 0.887 p < 0.001). Generally, DVHs calculated on 99mTc-MAA SPECT/CT and 90Y PET/CT gave comparable results, some discrepancies were observed particularly with those patients where SPECT and PET imaging presented a visual mismatching. CONCLUSION: A simplified 3D dosimetry methodology was implemented and tested retrospectively on patient data treated with 90Y resin spheres. Even if the clinical feasibility of our approach has to be further validated on an extended patient cohort, the preliminary results of our study highlight the potential of the implemented dosimetric tool for tumour dose assessment.

The value of radioembolisation therapy on metastatic liver tumours - a single centre experience.

OBJECTIVE: Local treatments used in metastatic liver tumours efficiently control the disease and survival. Transarterial radioembolisation (TARE) is a safely used locoregional treatment method. We aim to investigate the impact of TARE on different kinds of metastatic liver tumours and the effect of pre-treatment clinical findings. MATERIAL AND METHODS: The patients with metastatic liver tumours referred to our department for radioembolisation were retrospectively evaluated. All patients were given a Y-90 glass microsphere after being selected by the appropriate clinical and imaging criteria, lung shunt fraction levels, vascular investigation, and macro aggregated albumin (MAA) scintigraphy performed in the angiography unit. RESULTS: Thirty-four (17 women, 17 men) patients were suitable for the treatment. Patients were treated with 115.88±47.84 Gy Y-90 glass Microspheres. The mean survival rate was 14.59±12.59 months after treatment. Higher survival rates were detected in patients who had higher pre-treatment serum albumin levels. The optimum cut-off value of albumin to predict response to treatment was 4 g/dl with 88.89% sensitivity, 62.50% specificity, 72.73% PPV and 83.33% NPV. Furthermore, one unit increase in age increased mortality 1.152 times in our patient group. CONCLUSION: Radioembolisation is a safe and efficient method for controlling metastatic liver disease. Albumin levels significantly affect predicting response; higher albumin levels are related to higher survival rates. Furthermore, older age positively correlated with mortality rates in our patient group.

The Problematic PET: Using CT Albumin Tracer to Resect Suspicious Lymph Nodes Found on PET Scan in Pediatric Oncology Patients.

BACKGROUND: Management of small lymph nodes or lesions in dense nodal basins found on Positron Emission Tomography (PET) scans can be challenging to identify, access and locate intraoperatively. Herein we describe the first reported case series utilizing pre-operative CT-guided radionuclide-tagged macro-aggregated albumin (TC 99m MAA) for localization and resection of extra-pulmonary PET-avid lymph nodes in pediatric cancer patients. METHODS: Pediatric cancer patients (≤21 years) who underwent pre-operative TC 99m MAA localization of suspicious lymph nodes were identified and retrospectively reviewed. RESULTS: Ten procedures were performed on 10 children at our institution from 2017 to 2021. Median age was 14 [13, 18]; 70% were male. Primary tumor type was variable. Lymph nodes were in various nodal basins including the axilla, groin, neck, popliteal fossa, retroperitoneum, and mediastinum. Three patients underwent resection of both pulmonary and extra-pulmonary lesions during the same procedure. Median node size was 15 mm (range: 10 mm- 23 cm). In 60.0% of patients the localized lymph nodes of concern were non-palpable at the time of operation. In 90% of the patient, biopsy findings changed the course of disease management. CONCLUSION: Pre-operative labeling with TC 99m MAA is a safe and effective technique to facilitate the localization, biopsy, and resection of suspicious lymph nodes found on PET scans in pediatric cancer patients that are located in dense nodal basins. This technique enables accurate resection of small, concerning lymph nodes that might otherwise be difficult to operatively identify and excise; the resultant information can affect the staging and further treatment of these patients. LEVEL OF EVIDENCE: IV.