Single-photon Emission Computed tomography/X-ray Computed Tomography Research Articles

The relationship between the quantitative evaluation of thyroid bed uptake and the disappearance of accumulation in adjuvant radioactive iodine therapy for differentiated thyroid cancer.

Iodine-131 (I-131) radioactive iodine therapy (RAI) after total thyroidectomy is the standard treatment for patients with differentiated thyroid cancer (DTC). We investigated the relationship between the quantitative parameters of the iodine uptake and the disappearance of the accumulation in the thyroid bed in adjuvant therapy using a 1.11GBq or 3.70GBq dose of I-131. We retrospectively analyzed the cases of 40 patients with DTC who were treated with RAI at our institution between April 2017 and August 2019. The patients were treated with the I-131 dose of 1.11GBq (n = 25) or 3.70GBq (n = 15) after total thyroidectomy. The I-131 whole-body scan and hybrid single-photon emission computed tomography/X-ray computed tomography (SPECT/CT) were performed 3days after RAI. Using image analysis software, we measured the standardized uptake value (SUV) and absolute radioactivity concentration (kBq/ml) on the target lesions with the highest uptake in the thyroid bed. The median period from RAI to the evaluation of the absence of uptake of the thyroid bed was 6.75months. After RAI, uptake of the thyroid bed disappeared in 26 of the 40 patients. The disappearance rate was significantly higher in the 3.70GBq group than in the 1.11GBq group (86.7% vs. 52.0%, respectively; p = 0.029). However, there were no significant differences in the values of kBq/ml or SUV between the 1.11GBq group and 3.70GBq group. On the other hand, the group in which the uptake disappeared after RAI showed significantly higher kBq/ml max and kBq/ml mean values than the group in which the uptake did not disappear after RAI (p = 0.028, p = 0.032, respectively). The SUVmax and SUVmean also tended to be higher in the disappeared-uptake group than the not-disappeared-uptake group, but the differences were not significant (p = 0.166, p = 0.176, respectively). The quantitative evaluation might be useful as one of the predictive indicators of the disappearance of the accumulation of radioactive iodine in the thyroid bed.

Absolute radiotracer concentration measurement using whole-body solid-state SPECT/CT technology: in vivo/in vitro validation.

The accuracy of recently approved quantitative clinical software was determined by comparing in vivo/in vitro measurements for a solid-state cadmium-zinc-telluride SPECT/CT (single photon emission computed tomography/x-ray computed tomography) camera. Bone SPECT/CT, including the pelvic region in the field of view, was performed on 16 patients using technetium-99m methylene diphosphonic acid as a radiotracer. After imaging, urine samples from each patient provided for the measurement of in vitro radiopharmaceutical concentrations. From the SPECT/CT images, three users measured in vivo radiotracer concentration and standardized uptake value (SUV) for the bladder using quantitative software (Q.Metrix, GE Healthcare). Linear regression was used to validate any in vivo/in vitro identity relations (ideally slope = 1, intercept = 0), within a 95% confidence interval (CI). Thirteen in vivo/in vitro pairs were available for further analysis, after rejecting two as clinically irrelevant (SUVs > 100g/mL) and one as an outlier (via Cook's distance calculations). All linear regressions (R2 ≥ 0.85, P < 0.0001) provided identity in vivo/in vitro relations (95% CI), with SUV averages from all users giving a slope of 0.99 ± 0.25 and intercept of 0.14 ± 5.15g/mL. The average in vivo/in vitro residual difference was < 20%. Solid-state SPECT/CT imaging can reliably provide in vivo urinary bladder radiotracer concentrations within approximately 20% accuracy. This practical, non-invasive, in vivo quantitation method can potentially improve diagnosis and assessment of response to treatment. Graphical abstract.

Development of a Novel Imaging Agent for Determining Albumin Uptake in Solid Tumors.

The purpose of this study was to investigate the albumin-binding compound 111In-C4-DTPA as an imaging agent for the detection of endogenous albumin accumulation in tumors. 111In-C4-DTPA was injected in healthy nude mice for pharmacokinetic and biodistribution studies (10min, 1, 6, 24, and 48h, n = 4) and subsequently in tumor-bearing mice for single-photon emission computed tomography/X-ray-computed tomography (SPECT/CT) imaging studies. Four different human tumor xenograft models (LXFL529, OVXF899, MAXFTN401, and CXF2081) were implanted subcutaneously unilaterally or bilaterally (n = 4-8). After intravenous administration of 111In-C4-DTPA, SPECT/CT images were collected over 72h at 4-6 time points. Additionally, gamma counting was performed for the blood, plasma, lungs, heart, liver, spleen, kidneys, muscle, and tumors at 72h post-injection. 111In-C4-DTPA bound rapidly to circulating albumin upon injection, and the radiolabeled albumin conjugate thus formed was stable in murine and human serum. SPECT/CT images demonstrated a time-dependent uptake with a maximum of 2.7-3.8%ID/cm3 in the tumors at approximately 24h post-injection and mean tumor/muscle ratios in the range of 3.2-6.2 between 24 and 72h post-injection. The kidneys and bladder were the predominant elimination organs. Gamma counting at 72h post-injection showed 1.3-2.5%ID/g in the tumors and mean tumor/muscle ratios in the range of 4.9-9.4. 111In-C4-DTPA bound rapidly to circulating albumin upon injection and showed time-dependent uptake in the tumors demonstrating a potential for clinical application as a companion imaging diagnostic for albumin-binding anticancer drugs.

SPECT Imaging of Treatment-Related Tumor Necrosis Using Technetium-99m-Labeled Rhein.

Noninvasive imaging of treatment-induced necrosis is important to distinguish early responders from patients resistant to the treatment plan, enabling the tailored-made therapeutic intervention. The purpose of this study was to explore the feasibility of [99mTc]EDDA-HYNIC-2C-rhein for early assessment of tumor response to treatment. In vitro necrosis avidity of [99mTc]EDDA-HYNIC-2C-rhein was evaluated in human lung cancer A549 cells treated with hyperthermia. Single photon emission-computed tomography/X-ray-computed tomography (SPECT/CT) imaging was performed in rats bearing subcutaneous W256 tumor treated with combretastatin A-4 disodium phosphate (CA4P) and rats bearing orthotopic liver W256 tumor treated with a single microwave ablation. All rats were euthanized immediately after the imaging session for biodistribution and histology studies. The mechanism of necrosis avidity for the tracer was further explored by in vivo blocking experiment and in vitro histochemistry and fluorescence staining. The uptake of [99mTc]EDDA-HYNIC-2C-rhein in necrotic cells was significantly higher than that in viable cells (p < 0.05). SPECT/CT imaging showed that an obvious "hot spot" was observed in the CA4P-treated tumor while not in the control tumor at 5h after tracer injection. Ex vivo γ-counting revealed that the uptake of [99mTc]EDDA-HYNIC-2C-rhein in tumor was increased 3.5-fold in rats treated with CA4P compared with rats treated with vehicle. Autoradiography and corresponding H&E staining suggested that the higher overall radiotracer uptake in the treated tumors was attributed to the increased necrosis. Blocking with unlabeled HYNIC-2C-rhein demonstrated the specific binding of the radiotracer to necrotic tissues. The perfect match of autoradiograph and histochemistry staining and PI fluorescence staining revealed that necrosis avidity of the tracer may be attributable to intercalation with exposed DNA in necrotic tissues. [99mTc]EDDA-HYNIC-2C-rhein can image necrosis induced by anticancer therapy and holds potential for early assessment of treatment response.

99mTc-MIBI single photon emission computed tomography/computed tomography for the incidental detection of rare parathyroid carcinoma.

This study aimed to evaluate the characteristics of parathyroid carcinoma and to validate the diagnostic value of 99mTc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography/x-ray computed tomography (SPECT/CT) for differentiating between parathyroid carcinoma and hyperparathyroidism. Four consecutive patients with suspected primary hyperparathyroidism were enrolled in this study and underwent 99mTc-MIBI SPECT/CT, ultrasonography, enhanced CT, and MRI. Serum parathyroid hormone (PTH) and calcium were measured. All primary and recurrent lesions showed high focal uptake on 99mTc-MIBI image, whereas metastatic lymph nodes gave false negative results. The serum PTH was 165.14 ± 90.26 pmol/L, which declined rapidly after surgery. One patient with a persistently high PTH (147.5 pmol/L) after surgery presented with multiple lymphadenopathy in the neck. Higher expression of chromogranin A (CgA) further confirmed parathyroid carcinoma as a rare endocrine tumor. Parathyroid carcinoma is thus usually diagnosed incidentally based on nonspecific multiorgan symptoms of hypercalcemia and hyperparathyroidism. 99mTc-MIBI SPECT/CT may help to localize the parathyroid carcinoma, while MRI is valuable for detecting metastasis. Serum PTH and CgA serve as circulating biomarkers in parathyroid carcinoma, and raised levels of PTH and CgA together with locoregional lymphadenopathy may indicate parathyroid carcinoma. Further studies are needed.

Evaluation of Necrosis Avidity and Potential for Rapid Imaging of Necrotic Myocardium of Radioiodinated Hypocrellins.

Rapid noninvasive delineation of necrotic myocardium in ischemic regions is very critical for risk stratification and clinical decision-making but still challenging. This study aimed to evaluate the necrosis avidity of radioiodinated hypocrellins and its potential for rapidly imaging necrotic myocardium. The aggregation constants of four natural hypocrellins were analyzed by UV/vis spectroscopy. Then, they were radiolabeled with iodine-131 by iodogen oxidation method. Necrosis avidity of iodine-131-labeled hypocrellins was evaluated in rat models with reperfused liver infarction and muscular necrosis by gamma counting, autoradiography, and histopathology. Their pharmacokinetic properties were examined in normal rats. The potential of iodine-131-labeled hypomycin A ([131I]HD) for early imaging of necrotic myocardium was explored in rat models with reperfused myocardial infarction. Finally, the possible mechanism of necrosis avidity was investigated by in vitro DNA binding and in vivo blocking experiments. The aggregation constants of four hypocrellins were all much smaller than that of hypericin, a most studied necrosis avid agent. The radiochemical purities of the four radiotracers after purification were all greater than 95%, and more than 90% of tracers remained intact after incubation in rat serum for 24h. Among the four tracers, [131I]HD exhibited the highest necrotic to viable tissue uptake ratio and the fastest blood clearance. The necrotic myocardium could be clearly visualized 4h after injection of [131I]HD by single-photon emission computed tomography/X-ray computed tomography (SPECT/CT). DNA binding studies suggested that HD could bind to DNA through intercalation. Blocking studies demonstrated that uptake of [131I]HD in necrotic muscle could be significantly blocked by excess unlabeled HD and ethidium bromide with 67 and 60% decline at 6h after coinjection, respectively. [131I]HD can be used to rapidly visualize necrotic myocardium. The necrosis avidity mechanism of [131I]HD may be attributed to its binding to the exposed DNA in necrotic tissues.

Use of 99mTc-sestamibi Single-photon Emission Computed Tomography / X-ray Computed Tomography in the Diagnosis of Hybrid Oncocytic / Chromophobe Tumor in a Pediatric Patient

The differential diagnosis of solid renal neoplasms in adolescence includes aggressive malignancy and indolent oncocytic tumors, which are typically indistinguishable using conventional imaging. We report the use of 99mTc-sestamibi single-photon emission computed tomography / x-ray computed tomography (SPECT/CT) in characterizing enhancing renal neoplasms in a pediatric patient. Genetic testing suggested a hereditary syndrome associated with aggressive malignancy, whereas renal mass biopsy suggested an oncocytic tumor. 99mTc-sestamibi SPECT/CT indicated probable oncocytomas or hybrid oncocytic / chomophobe tumors. Enucleative resection was performed with final pathology demonstrating hybrid oncocytic / chomophobe tumors. This case highlights the potential utility of 99mTc-sestamibi SPECT/CT in characterizing indeterminate enhancing renal neoplasm in pediatric patients.

Evaluation of Radioiodinated 1,4-Naphthoquinones as Necrosis Avid Agents for Rapid Myocardium Necrosis Imaging

Identifying necrotic myocardium in ischemic regions is of great importance for risk stratification and clinical decision-making. However, rapid noninvasive imaging of necrotic myocardium is still challenging. This study sought to evaluate the potential of 1,4-naphthoquinones to rapidly visualize necrotic myocardium and the possible mechanisms of necrosis avidity. Six 1,4-naphthoquinones were radiolabeled with iodine-131 and the necrosis avidity was estimated in mouse models with muscular necrosis by gamma counting and autoradiography. The necrotic myocardium imaging property and biodistribution of [131I]naphthazarin (6) were determined in rat models with re-perfused myocardial infarction. A possible mechanism of necrosis avidity was explored by in vitro DNA-binding and in vivo blocking experiments. The radiochemical purities of the six radiotracers were greater than 95%. The uptakes in necrotic muscles of all six radiotracers were higher than those in viable muscles, and [131I]naphthazarin (6) showed the highest necrotic-to-viable ratio and necrosis-to-blood ratio at all tested time points. The necrotic myocardium could be clearly visualized by single-photon emission computed tomography/x-ray computed tomography (SPECT/CT) using [131I]naphthazarin (6) as early as 3h post-injection. Post-mortem biodistribution showed the uptake of [131I]naphthazarin (6) in necrotic myocardium was 11.67-fold higher than that in viable myocardium. Absorption spectra and emission spectra suggested naphthazarin (6) could bind to DNA through intercalation. The uptake of [131I]naphthazarin (6) in necrotic muscle could be significantly blocked by excessive ethidium bromide (a typical DNA intercalator) and cold naphthazarin (6) with 63.49 and 71.96% decline at 3h post-injection in vivo, respectively. 1,4-Naphthoquinones retained necrosis avidity and [131I]naphthazarin (6) rapidly visualized necrotic myocardium. The necrosis avidity mechanism of [131I]naphthazarin (6) may be attributed to its binding with exposed DNA in necrotic tissues.

Navigation of a robot-integrated fluorescence laparoscope in preoperative SPECT/CT and intraoperative freehand SPECT imaging data: a phantom study.

Robot-assisted laparoscopic surgery is becoming an established technique for prostatectomy and is increasingly being explored for other types of cancer. Linking intraoperative imaging techniques, such as fluorescence guidance, with the three-dimensional insights provided by preoperative imaging remains a challenge. Navigation technologies may provide a solution, especially when directly linked to both the robotic setup and the fluorescence laparoscope. We evaluated the feasibility of such a setup. Preoperative single-photon emission computed tomography/X-ray computed tomography (SPECT/CT) or intraoperative freehand SPECT (fhSPECT) scans were used to navigate an optically tracked robot-integrated fluorescence laparoscope via an augmented reality overlay in the laparoscopic video feed. The navigation accuracy was evaluated in soft tissue phantoms, followed by studies in a human-like torso phantom. Navigation accuracies found for SPECT/CT-based navigation were 2.25 mm (coronal) and 2.08 mm (sagittal). For fhSPECT-based navigation, these were 1.92 mm (coronal) and 2.83 mm (sagittal). All errors remained below the <1-cm detection limit for fluorescence imaging, allowing refinement of the navigation process using fluorescence findings. The phantom experiments performed suggest that SPECT-based navigation of the robot-integrated fluorescence laparoscope is feasible and may aid fluorescence-guided surgery procedures.

Determination of the biodistribution and dosimetry of 123I-FP-CIT in male patients with suspected Parkinsonism or Lewy body dementia using planar and combined planar and SPECT/CT imaging

In this study, 123I-FP-CIT biodistribution and dosimetry was determined in 10 adult male patients using planar gamma camera imaging alone or in combination with single photon emission computed tomography /X-ray computed tomography (SPECT/CT) imaging. Dosimetric assessment using planar plus SPECT/CT imaging resulted in significantly different estimates of organ-absorbed doses compared to estimates based on planar imaging alone. We conclude that the use of complementary SPECT/CT measurements in biodistribution studies is valuable for determining the organ doses more accurately.

Diagnosis of Bronchobiliary Fistula-Utility of 99m Tc-Mebrofenin Scan and SPECT/CT.

A broncho-biliary fistula (BBF) is difficult to diagnose in the absence of biliptysis. We present here the case of a 3-year-old female child who developed a BBF that was diagnosed on a 99mTc-Mebrofenin hepatobiliary (HIDA) scan. In this case, the cause was due to a complicated amoebic liver abscess that progressively ruptured through the right pleural space. We have also demonstrated tracer accumulation in the posterobasal part of the right lung along with consolidation, which is direct evidence that bile is accumulating in the lung on single-photon emission computed tomography/X ray computed tomography (SPECT/CT) (Figs. 1 and ​and22).

Impact of Indium-111 Oxine Labelling on Viability of Human Mesenchymal Stem Cells In Vitro, and 3D Cell-Tracking Using SPECT/CT In Vivo

This study investigates the effects of (111)In-oxine incorporation on human mesenchymal stem cells' (hMSC) biology and viability, and the applicability of (111)In-oxine for single-photon emission computed tomography/X-ray computed tomography (SPECT/CT) monitoring of hMSC in vivo. HMSC were labelled with 10 Bq/cell. Cellular retention of radioactivity, cell survival, and migration were evaluated over 48 h. Metabolic activity was assessed over 14 days and the hMSC's stem cell character was evaluated. Serial SPECT/CT was performed after intra-osseous injection to athymic rats over 48 h. Labelling efficiency was 25%, with 61% of incorporated (111)In remaining in the hMSC at 48 h. The radiolabelling was without effect on cell viability, stem cell character, and plasticity, whereas metabolic activity and migration were significantly reduced. Grafted cells could be imaged in situ with SPECT/CT. (111)In-oxine labelling moderately impaired hMSC's functional integrity while preserving their stem cell character. Combined SPECT/CT imaging of (111)In-oxine-labelled hMSC opens the possibility for non-invasive sequential monitoring of therapeutic stem cells.