Single Photon Emission Computed Tomography With Computed Tomography Research Articles

Abstract 2027: Enhancing Cell-based Therapies With Peptide-modified Thermoresponsive Citrate-based Biomaterials For Treatment Of Critical Limb Ischemia

Introduction: Critical limb ischemia (CLI) causes severe morbidity and mortality with limited treatment options. Cell-based therapy has potential to advance treatment outcomes but faces challenges in cell survival and engraftment during delivery. We hypothesize that an antioxidant niche that promotes cell adhesion and spreading will improve cell engraftment and survival rate, with the goal of limb salvage through improved perfusion. Methods: Thermoresponsive poly(polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN) was synthesized and conjugated with laminin-derived (A5G81) or VEGF-mimic (QK) peptides. Human umbilical vein endothelial cells (HUVECs) expressing human sodium iodine symporter (hNIS) were mixed with materials and intramuscularly injected into nude mice hindlimbs and monitored with Single Photon Emission Computed Tomography with Computed Tomography (SPECT/CT) for cell survival. Next, a hindlimb ischemia model was used to assess the efficacy of cell delivery by evaluating limb perfusion, tissue loss, functional impairment and histological examination. Results: Cells delivered with PBS or PPCN demonstrated poor cell survival, with over 90% cell loss by day 7 ( Figure 1a ). In contrast, cells delivered with PPCN-A5G81 and PPCN-QK exhibited robust SPECT signal levels for up to four weeks ( Figure 1a,b ). In the hindlimb ischemia model, materials or cells alone did not demonstrate improvement in any of the parameters over the PBS control. However, cells delivered with PPCN-A5G81 and PPCN-QK showed significantly higher blood perfusion ( Figure 1c-e ), with improved tissue salvage and motor functions ( Figure 1f-i ) for both male and female mice. Conclusion: PPCN modified with A5G81 and QK promotes cell spreading, proliferation, survival, and tissue regeneration, with potential for more effective cell-based therapies for CLI.

Contribution of CT scan to patient's radiation exposure in parathyroid SPECT/CT scintigraphy

IntroductionDual phase technetium-99mTc-methoxy isobutyl isonitrile (MIBI) single-photon emission computed tomography with computed tomography (SPECT/CT) may be the most accurate conventional imaging approach for localization of enlarged parathyroid gland (EPG). The imaging is based on the radiopharmaceutical (RP) retention in EPG compared to washout from normal thyroid and normal parathyroid glands. This study aimed to estimate and optimize the contribution of computed tomography (CT) scan and scan range to effective dose (ED) in dual-phase MIBI SPECT/CT parathyroid scintigraphy. MethodsThe study included seventy-four patients; thirty-seven with reduced and thirty-seven with extended CT scan range. The ED caused by the CT scan was calculated using Dose Length Product (DLP) data and estimated using the Imaging Performance Assessment of CT scanners (ImPACT) calculator. ResultsFor all patients, the contribution of CT to the ED in a combined SPECT/CT examination was 2.62 ± 0.29 mSv (48%). The contribution of CT to the total ED was 1.8 ± 0.18 mSv (33%) when using reduced and 3.44 ± 0.23 mSv (64%) when using extended scan range. The DLP and ED were statistically significantly different between the reduced and extended CT scan range (p < 0.001) in the first and second phases. The individual organ dose was reduced from 8% to 94%. ConclusionThe hybrid SPECT/CT improves the interpretation of nuclear medicine images and also increases the radiation dose to the patient. An adequately defined CT scan range on SPECT/CT imaging, can significantly reduce a patient's ED. Implications for practiceThe research findings showed that knowledge of anatomy, pathology and technology can provide optimising diagnostic procedures and reduce patient ED after SPECT/CT scans.

Diagnostic importance of Bone scan and SPECT-CT in atypical cases of CRPS presenting to pain clinic: A case report

Establishing a diagnosis of complex regional pain syndrome (CRPS) is challenging and often requires a multidisciplinary approach. Skeletal scintigraphy (bone scan) can be helpful in diagnosing and staging CRPS. Presented here is an interesting case of the right upper extremity and pectoral region pain, which upon evaluation with skeletal scintigraphy and single photon emission computed tomography with computed tomography (SPECT-CT) turned out to be Pancoast tumor.

Applications of SPECT/CT in the Evaluation of Spinal Pathology: A Review.

Accurate identification of pain generators in the context of low back and spine-related pain is crucial for effective treatment. This review aims to evaluate the potential usefulness of single photon emission computed tomography with computed tomography (SPECT/CT) as an imaging modality in guiding clinical decision-making. A broad scoping literature review was conducted to identify relevant studies evaluating the use of SPECT/CT in patients with spine-related pain. Studies were reviewed for their methodology and results. SPECT/CT appears to have advantages over traditional modalities, such as magnetic resonance imaging and CT, in certain clinical scenarios. It may offer additional information to clinicians and improve the specificity of diagnosis. However, further studies are needed to fully assess its diagnostic accuracy and clinical utility. SPECT/CT is a promising imaging modality in the evaluation of low back pain, particularly in cases where magnetic resonance imaging and CT are inconclusive or equivocal. However, the current level of evidence is limited, and additional research is needed to determine its overall clinical relevance. SPECT/CT may have a significant impact on clinical decision-making, particularly in cases in which traditional imaging modalities fail to provide a clear diagnosis. Its ability to improve specificity could lead to more targeted and effective treatment for patients with spinal pathology.

Validation of single-photon emission computed tomography with computed tomography and lymphoscintigraphy for sentinel lymph node identification in cervical cancer.

To compare single-photon emission computed tomography with computed tomography (SPECT/CT) and lymphoscintigraphy (LSG) for the detection of sentinel lymph nodes (SLNs) in patients with early-stage cervical cancer. This hospital-based, single-center, retrospective study included 128 patients with cervical cancer (aged >18 years) treated between 2014 and 2022. Injection of 99 m Technetium-labeled phytate into the uterine cervix was used to detect pelvic SLNs. SNL identification rates and locations were analyzed for preoperative LSG and SPECT/CT. Median age and body mass index of patients were 40 years (range, 20-78 years) and 21.7 kg/m2 (range, 16-40 kg/m2 ), respectively. There was no significant difference in overall identification rates (identification of at least one SLN) of SLNs between SPECT/CT (91%) and LSG (88%). There was no significant difference in bilateral SLN identification rates between SPECT/CT (66%) and LSG (65%). A total of 219 pelvic SLNs (110 right and 109 left hemipelvis) were identified by SPECT/CT; the most frequent locations were the obturator (122 SLNs, 56%) and external iliac (67 SLNs, 30%). SPECT/CT and LSG showed high SLN identification rates in patients with cervical cancer, and there was no significant difference in overall or bilateral SLN identification rates between the two techniques.

New index to assess the extent of bone disease in patients with prostate cancer using SPECT/CT.

Assessing the extent of bone metastases in patients with prostate cancer is very important to predict patient prognosis. Therefore, the bone scan index (BSI), which is easy to use, has been used; however, the accuracy is not that high. In this study, we proposed a new index for the extent of bone disease using single-photon emission computed tomography with computed tomography (SPECT/CT) images and assessed the accuracy of calculation. In this study, a total of 46 bone scans from 12 patients with prostate cancer treated for bone metastases with Radium-223 were included. Whole-body planar images were obtained 150-180min after an intravenous injection of 99mTc-methylene diphosphonate, and cervical-to-pelvic SPECT/CT was immediately obtained. The total bone volume (TBV) and regional metabolic bone volume (MBV) were defined as Hounsfield unit of > 120, standardized uptake value (SUV) of > 0.5, and SUV of > 5-8 in four levels, respectively. Bone metabolism volumetric index (BMVI) was calculated as the percentage of the total MBV divided by TBV. The variability of the TBV measurement was evaluated by the percentage coefficient of variance (%CV) of TBV within individual patients. We evaluated the correlation of TBV with age, height, weight, and body mass index and the correlation and agreement between BSI and BMVI. The mean and %CV of TBV were 4661.7 cm3 and 2.8%, respectively, and TBV was strongly correlated with body weight. BMVI was significantly higher than BSI and correlated with alkaline phosphatase. For patients with progressive bone metastases, BSI was clearly underestimated, whereas BMVI was elevated. Although assessed in a small number of cases, the new index for assessing the extent of bone disease using SPECT/CT imaging was highly value than BSI and was significantly correlated with alkaline phosphatase. Therefore, this study suggests that BMVI could improve the low sensitivity of BSI in patients with low extent of disease grade.

Thyroid scintigraphy and hybrid SPECT/CT in a rare case of dual ectopic thyroid.

Dual ectopic thyroid (DET) is a rare disorder occurring as a result of aberrant embryonic development characterized by simultaneous presence of thyroid tissue at two ectopic sites. 99mTc-Pertechnetate thyroid scintigraphy remains gold standard in confirming ectopic thyroid tissue. This case highlights the importance of thyroid scintigraphy and Single Photon Emission Computed Tomography with Computed Tomography (SPECT/CT) in evaluation of ectopic thyroid tissue and DET that manifested itself during patients' pregnancy.

Preoperative detection of sentinel lymph node in patients with endometrial cancer - comparison of planar lymphoscintigraphy, spect and SPECT/CT.

Sentinel lymph node (SLN) mapping allows minimal invasive assessment of lymph node status in patients with early-stage endometrial cancer (EC). Intraoperative detection of SLNs is based on the results obtained from preoperative nuclear medical images. The purpose of this study was to compare the data obtained from planar lymphoscintigraphy (PL), single-photon emission computed tomography (SPECT), and SPECT with computed tomography (SPECT/CT) for preoperative SLN detection in patients with EC. A total of 44 images in 22 patients with early-stage EC (22 PL, 9 SPECT and 13 SPECT/CT) were analyzed. The scans were performed in the period 2018-2020 at the Institute of Pathophysiology and Nuclear Medicine in Skopje. Thirteen patients underwent PL and SPECT/CT and nine patients underwent PL and SPECT after cervical injection of 4 mCi 99mTc-SENTI-SCINT on the day of surgery. Descriptive statistics, Wilcoxon Matched Pairs Test, and Spearman rank R coefficient were used for data analyses. Twenty-two patients with mean age of 61.1 ± 7.5 and body mass index (BMI) 34.62 ± 6.4 kg/m2 were included in the study. In four patients (18.2%) SLN was not detected on PL. Detection rate on SPECT and SPECT/CT was 100%. The average number of detected SLN was 1.4 ± 1.05, 2.2 ± 1.1 и 2.15 ± 1.1 on PL, SPECT and SPECT/CT respectively. We found a statistically significant difference in the number of detected SLNs on PL vs SPECT/CT (p = 0.0077). The most common SLN location on SPECT/CT was the right internal iliac followed by the left common iliac region. The results of the presented study indicate a higher diagnostic value of SPECT/CT in terms of SLN detection and exact anatomic localization as compared to planar lymphoscintigraphy (PL).

Image-Guided Biopsy for Relapsed Neuroblastoma: Focus on Safety, Adequacy for Genetic Sequencing, and Correlation of Tumor Cell Percent With Quantitative Lesion MIBG Uptake.

Many novel therapies for relapsed and refractory neuroblastoma require tumor tissue for genomic sequencing. We analyze our experience with image-guided biopsy in these patients, focusing on safety, yield, adequacy for next-generation sequencing (NGS), and correlation of tumor cell percent (TC%) with quantitative uptake on 123I-meta-iodobenzylguanidine (MIBG) single-photon emission computed tomography with computed tomography (SPECT/CT). An 11-year retrospective review of image-guided biopsy on 66 patients (30 female), with a median age of 8.7 years (range, 0.9-49 years), who underwent 95 biopsies (55 bone and 40 soft tissue) of relapsed or refractory neuroblastoma lesions was performed. There were seven minor complications (7%) and one major complication (1%). Neuroblastoma was detected in 88% of MIBG- or fluorodeoxyglucose-avid foci. The overall NGS adequacy was 69% (64% in bone and 74% in soft tissue, P = .37). NGS adequacy within neuroblastoma-positive biopsies was 88% (82% bone and 96% soft tissue, P = .11). NGS-adequate biopsies had a greater mean TC% than inadequates (51% v 18%, P = .03). NGS-adequate biopsies had a higher mean number of needle passes (7.5 v 3.4, P = .0002). The mean tissue volume from NGS-adequate soft-tissue lesions was 0.16 cm3 ± 0.12. Lesion:liver and lesion:psoas MIBG uptake ratios correlated with TC% (r = 0.74, r = 0.72, and n = 14). Mean TC% in NGS-adequate samples was 51%, corresponding to a lesion:liver ratio of 2.9 and a lesion:psoas ratio of 9.0. Thirty percent of biopsies showed an actionable ALK mutation or other therapeutically relevant variant. Image-guided biopsy for relapsed or refractory neuroblastoma was safe and likely to provide NGS data to guide therapy decisions. A lesion:liver MIBG uptake ratio of ≥ 3 or a lesion:psoas ratio of > 9 was associated with a TC% sufficient to deliver NGS results.

Optimization of cross-calibration factor for quantitative bone SPECT without attenuation and scatter correction in the lumbar spine: head-to-head comparison with attenuation and scatter correction.

Quantitative single-photon emission computed tomography (SPECT) with computed tomography (SPECT/CT) is known to improve diagnostic performance. Although SPECT-alone systems are used widely, accurate quantitative SPECT using these systems is challenging. This study aimed to improve the accuracy of quantitative bone SPECT of the lumbar spine with the SPECT-alone system. The cross-calibration factor (CCF) was measured using three kinds of phantoms and the optimal values were determined. The recovery coefficient with and without attenuation and scatter correction (ACSC) were compared. Bone SPECT/CT was performed on 93 consecutive patients with prostate cancer, and the standardized uptake values (SUVs) were compared using the respective CCFs. The first 60 patients were classified according to body weight, and the correlation coefficient between SUVs with and without ACSC were calculated; the slopes were defined as body weight-based coefficients (BWCs). In the remaining 33 patients, the SUV was adjusted according to BWC, and the accuracy of the adjustment was verified. The quantitative SPECT values obtained from the CCF using SIM2 bone phantom showed nearly accurate radioactivity concentrations, even without ACSC. The recovery coefficients with and without ACSC were similar. Unadjusted SUVs with and without ACSC were strongly correlated; however, SUVs without ACSC were significantly higher than those with ACSC (P < 0.0001). The mean difference between the SUVs with and without ACSC disappeared when the SUVs without ACSC were adjusted by BWC (P = 0.9814). Our cross-calibration method for quantitative bone SPECT enables interpretation with a harmonized SUV even in SPECT-alone systems.

Nuclear Medicine Imaging in Neuroblastoma: Current Status and New Developments.

Neuroblastoma is the most common extracranial solid malignancy in children. At diagnosis, approximately 50% of patients present with metastatic disease. These patients are at high risk for refractory or recurrent disease, which conveys a very poor prognosis. During the past decades, nuclear medicine has been essential for the staging and response assessment of neuroblastoma. Currently, the standard nuclear imaging technique is meta-[123I]iodobenzylguanidine ([123I]mIBG) whole-body scintigraphy, usually combined with single-photon emission computed tomography with computed tomography (SPECT-CT). Nevertheless, 10% of neuroblastomas are mIBG non-avid and [123I]mIBG imaging has relatively low spatial resolution, resulting in limited sensitivity for smaller lesions. More accurate methods to assess full disease extent are needed in order to optimize treatment strategies. Advances in nuclear medicine have led to the introduction of radiotracers compatible for positron emission tomography (PET) imaging in neuroblastoma, such as [124I]mIBG, [18F]mFBG, [18F]FDG, [68Ga]Ga-DOTA peptides, [18F]F-DOPA, and [11C]mHED. PET has multiple advantages over SPECT, including a superior resolution and whole-body tomographic range. This article reviews the use, characteristics, diagnostic accuracy, advantages, and limitations of current and new tracers for nuclear medicine imaging in neuroblastoma.

Proof of Concept Study for Increasing Tenascin-C-Targeted Drug Delivery to Tumors Previously Subjected to Therapy: X-Irradiation Increases Tumor Uptake

Simple SummaryWe hypothesized that an agent recognizing a specific factor, which is involved in tissue injury repair, could achieve the goal of delivering an additional antitumor agent to tumors during tissue repair after initial anticancer therapy. To demonstrate our concept, the present study employed tenascin-C (TNC) as a target molecule and radiation as initial therapy. Increased TNC expression was observed in tumors after radiation exposure in a pancreatic cancer mouse model. Of our three anti-TNC antibodies, the antibody 3–6 showed statistically significant higher tumor uptake compared with non-irradiated tumors in the by biodistribution and single-photon emission computed tomography with computed tomography studies. This finding strongly supports our concept. Our proposed therapeutic strategy could result in better outcomes for patients with treatment-refractory cancer.In treatment-refractory cancers, tumor tissues damaged by therapy initiate the repair response; therefore, tumor tissues must be exposed to an additional burden before successful repair. We hypothesized that an agent recognizing a molecule that responds to anticancer treatment-induced tissue injury could deliver an additional antitumor agent including a radionuclide to damaged cancer tissues during repair. We selected the extracellular matrix glycoprotein tenascin-C (TNC) as such a molecule, and three antibodies recognizing human and murine TNC were employed to evaluate X-irradiation-induced changes in TNC uptake by subcutaneous tumors. TNC expression was assessed by immunohistochemical staining of BxPC-3 tumors treated with or without X-irradiation (30 Gy) for 7 days. Antibodies against TNC (3–6, 12–2–7, TDEAR) and a control antibody were radiolabeled with 111In and injected into nude mice having BxPC-3 tumors 7 days after X-irradiation, and temporal uptake was monitored for an additional 4 days by biodistribution and single-photon emission computed tomography with computed tomography (SPECT/CT) studies. Intratumoral distribution was analyzed by autoradiography. The immunohistochemical signal for TNC expression was faint in nontreated tumors but increased and expanded with time until day 7 after X-irradiation. Biodistribution studies revealed increased tumor uptake of all three 111In-labeled antibodies and the control antibody. However, a statistically significant increase in uptake was evident only for 111In-labeled 3–6 (35% injected dose (ID)/g for 30 Gy vs. 15% ID/g for 0 Gy at day 1, p < 0.01), whereas limited changes in 111In-labeled TDEAR2, 12–2–27, and control antibody were observed (several % ID/g for 0 and 30 Gy). Serial SPECT/CT imaging with 111In-labeled 3–6 or control antibody provided consistent results. Autoradiography revealed noticeably stronger signals in irradiated tumors injected with 111In-labeled 3–6 compared with each of the nonirradiated tumors and the control antibody. The signals were observed in TNC-expressing stroma. Markedly increased uptake of 111In-labeled 3–6 in irradiated tumors supports our concept that an agent, such as an antibody, that recognizes a molecule involved in tissue injury repair, such as TNC, could enhance drug delivery to tumor tissues that have undergone therapy. The combination of antibody 3–6 coupled to a tumoricidal drug and conventional therapy has the potential to achieve better outcomes for patients with refractory cancer.

Impact of Resolution Recovery in Quantitative 99mTc SPECT/CT Cardiac Phantom Studies

BackgroundThe aim of this study was to validate the quantitative accuracy of single photon emission computed tomography with computed tomography (SPECT/CT) images in cardiac phantom studies. The study was performed by assessing the effect of resolution recovery (RR) when using half-time of imaging acquisition in cardiac phantom. MethodsThe SPECT/CT images of the anthropomorphic phantom with a cardiac insert, liver, lung, and spine were acquired using the GE Discovery (NM/CT 670) SPECT/CT system. Different concentration activity ratios for different organ (10:10:1:0, cardiac:liver:background:lung) regions were acquired by using full- and half-time protocols for 643 and 1283 voxel sizes that were reconstructed using filtered back projection (FBP) method and 3D ordered subset expectation maximization (3D-OSEM). Attenuation correction and scatter correction were applied to both reconstructions, whereas the RR only can be applied for 3D-OSEM. The data were analyzed and reported in terms of absolute recovery coefficient percentage between the cardiac insert and background activity concentration. Another parameter used to assess the quantitative accuracy for defect region was the relative error percentage. ResultsThe result of recovery coefficient percentage shows that the 3D-OSEM reconstruction with the RR gives the highest percentage estimation accuracy of 70% of activity recovery in the cardiac phantom wall compared with FBP (10.6%). The relative error percentage for reconstructed SPECT/CT images using 3D-OSEM reconstruction with RR shows the least error compared with FBP (21% vs. 45.1%) both in the full-and half-time acquisition of images with a larger number of matrix size used. Conclusions3D-OSEM reconstruction with the RR is beneficial in giving better quantitative evaluation with a good resolution myocardial perfusion image. To accomplish this, a larger matrix size is required for 3D-OSEM reconstruction with the RR and it demonstrated an improvement in image resolution and increased quantitative accuracy of the final reconstructed SPECT/CT images.

The Human Sodium Iodide Symporter as a Reporter Gene for Studying Middle East Respiratory Syndrome Coronavirus Pathogenesis.

Single photon emission computed tomography (SPECT) is frequently used in oncology and cardiology to evaluate disease progression and/or treatment efficacy. Such technology allows for real-time evaluation of disease progression and when applied to studying infectious diseases may provide insight into pathogenesis. Insertion of a SPECT-compatible reporter gene into a virus may provide insight into mechanisms of pathogenesis and viral tropism. The human sodium iodide symporter (hNIS), a SPECT and positron emission tomography reporter gene, was inserted into Middle East respiratory syndrome coronavirus (MERS-CoV), a recently emerged virus that can cause severe respiratory disease and death in afflicted humans to obtain a quantifiable and sensitive marker for viral replication to further MERS-CoV animal model development. The recombinant virus was evaluated for fitness, stability, and reporter gene functionality. The recombinant and parental viruses demonstrated equal fitness in terms of peak titer and replication kinetics, were stable for up to six in vitro passages, and were functional. Further in vivo evaluation indicated variable stability, but resolution limits hampered in vivo functional evaluation. These data support the further development of hNIS for monitoring infection in animal models of viral disease.IMPORTANCE Advanced medical imaging such as single photon emission computed tomography with computed tomography (SPECT/CT) enhances fields such as oncology and cardiology. Application of SPECT/CT, magnetic resonance imaging, and positron emission tomography to infectious disease may enhance pathogenesis studies and provide alternate biomarkers of disease progression. The experiments described in this article focus on insertion of a SPECT/CT-compatible reporter gene into MERS-CoV to demonstrate that a functional SPECT/CT reporter gene can be inserted into a virus.

Comparison between single photon emission computed tomography with computed tomography and planar scintigraphy in sentinel node biopsy in breast cancer patients

ObjectiveRadio-guided sentinel node (SN) biopsy is a standard method used in the treatment of early breast cancer. Single photon emission computed tomography with computed tomography (SPECT/CT) has been commonly used for SN detection. SPECT/CT adds precise anatomical information of SN sites, and it is reported that more SNs may be detectable on SPECT/CT than on planar imaging. We here investigate which breast cancer patients have benefited from SPECT/CT over planar imaging.MethodsA total of 273 breast cancer patients including 80 with ipsilateral breast tumor relapse (IBTR) underwent both multiple-view planar imaging and SPECT/CT for SN detection. The number of SNs, the patients who had benefitted from SPECT/CT, and the SN procedure failure rate were compared between SPECT/CT and planar imaging. Factors influencing the visualization of para-sternal and ipsilateral level II, III nodes, and contralateral axillary nodes were also analyzed using logistic regression analysis.ResultsThe number of hot spots did not differ between SPECT/CT and multiple-view planar imaging. Eight contaminated patients and 52 patients with visualized extra-level I axillary nodes benefited from identifying precise anatomical sites. Even though radioactive nodes could be harvested in most (192/193) of the non-IBTR patients (7/8 in non-SN visible patients), no radioactive nodes could be found during surgery in 11 of 80 IBTR patients. Axillary surgery (dissection) increased the visualization of para-sternal and level II, III axillary nodes, and previous irradiation increased the visualization of contralateral axillary nodes.ConclusionMultiple-view planar imaging was equivalent to SPECT/CT for depicting hot nodes for radio-guided SN detection in breast cancer. SPECT/CT was useful when precise anatomical information was necessary, especially regarding sentinel lymph nodes other than ipsilateral axilla. Logistic regression analysis revealed that axillary surgery (dissection) increased the visualization of para-sternal and level II, III axillary nodes, and the only relevant factor influencing visualization of contralateral axillary SNs was previous radiation to the breast.

Functioning Mediastinal Paraganglioma Associated with a Germline Mutation of von Hippel-Lindau Gene.

We report the case of a 21-year old woman presenting with high blood pressure and raised normetanephrine levels. Indium-111-pentetreotide single photon-emission computed tomography with computed tomography (SPECT/CT) and 2-deoxy-2-[fluorine-18]fluoro-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging showing isolated tracer-uptake by a 2 cm tumor close to the costovertebral angle of the third thoracic vertebra. Thoracic surgery led to normalization of normetanephrine levels. Histological findings were consistent with the presence of a paraganglioma. Mutations in SDHA, SDHB, SDHC, SDHD, RET, SDHAF2, TMEM127, MAX, NF1, FH, MDH2, and EPAS1 were absent, but a heterozygous missense mutation, c.311G > T, was found in exon 1 of the von Hippel-Lindau gene, VHL, resulting in a glycine to valine substitution in the VHL protein at position 104, p.Gly104Val. This same mutation was found in both the mother and the 17-year old sister in whom a small retinal hemangioblastoma was also found. We diagnose an unusual functional mediastinal paraganglioma in this young patient with a germline VHL gene mutation, a mutation previously described as inducing polycythemia and/or pheochromocytoma but not paraganglioma or retinal hemangioblastoma.

The added value of SPECT-CT for the identification of sentinel lymph nodes in early stage oral cancer

PurposeTo assess the role of single-photon emission computed tomography with computed tomography (SPECT-CT) for the identification of sentinel lymph nodes (SLNs) in patients with early stage (T1–T2) oral cancer and a clinically negative neck (cN0).MethodsIn addition to planar lymphoscintigraphy, SPECT-CT was performed in 66 consecutive patients with early stage oral cancer and a clinically negative neck. The addition of SPECT-CT to planar images was retrospectively analyzed for the number of additional SLNs, more precise localization of SLNs, and importance of anatomical information by a team consisting of a nuclear physician, surgeon, and investigator.ResultsIdentification rate for both imaging modalities combined was 98% (65/66). SPECT-CT identified 15 additional SLNs in 14 patients (22%). In 2/15 (13%) of these additional SLNs, the only metastasis was found, resulting in an upstaging rate of 3% (2/65). In 20% of the patients with at least one positive SLN, the only positive SLN was detected due to the addition of SPECT-CT. SPECT-CT was considered to add important anatomical information in two patients (3%). In 5/65 (8%) of the patients initially scored SLNs on planar lymphoscintigrams were scored as non-SLNs when SPECT-CT was added. There were four false-negative SLN biopsy procedures in this cohort.ConclusionsThe addition of SPECT-CT to planar lymphoscintigraphy is recommended for the identification of more (positive) SLNs and better topographical orientation for surgery in sentinel lymph node biopsy for early stage oral cancer.

Clinical Application of Technetium-99m-Labeled Red Blood Cells Subcutaneous Radionuclide Venography and Abdominal/Pelvic Hybrid SPECT/CT Imaging in Patients with Suspicion of Proximal Deep Vein Thrombosis

Technetium-99m-labeled red blood cells subcutaneous radionuclide venography can apply to evaluate deep venous flow of lower extremities. We introduce additional abdominal/pelvic hybrid SPECT/CT (single-photon emission computed tomography with computed tomography) to scrutinize the proximal deep venous flow defects in the iliac vein. SPECT/CT imaging is collected when disturbed or asymmetrical iliac venous flow is noted on the planar imaging of Tc-99m-labeled red blood cells subcutaneous radionuclide venography. The region of SPECT/CT imaging includes abdominal aorta, inferior vena cava and bilateral iliac vessels. We present three cases with suspicion of deep vein thrombosis in the iliac vein. Tc-99m-labeled red blood cells subcutaneous radionuclide venography with SPECT/CT revealed not only provides us the venous flow but also other information including abnormal vessel structure, space-occupying lesion and abnormality in other organs. In conclusion, if disturbed or asymmetrical iliac venous flow and abnormal collateral venous drainage in the abdomen are noted on the Tc-99mlabeled red blood cells subcutaneous radionuclide venography, SPECT/CT imaging may arrange for further information and differential diagnosis of lower extremities swelling; not only in detecting deep vein thrombosis.

Optimisation of Fluorescence Guidance During Robot-assisted Laparoscopic Sentinel Node Biopsy for Prostate Cancer

BackgroundThe hybrid tracer was introduced to complement intraoperative radiotracing towards the sentinel nodes (SNs) with fluorescence guidance. ObjectiveImprove in vivo fluorescence-based SN identification for prostate cancer by optimising hybrid tracer preparation, injection technique, and fluorescence imaging hardware. Design, setting, and participantsForty patients with a Briganti nomogram–based risk >10% of lymph node (LN) metastases were included. After intraprostatic tracer injection, SN mapping was performed (lymphoscintigraphy and single-photon emission computed tomography with computed tomography (SPECT-CT)). In groups 1 and 2, SNs were pursued intraoperatively using a laparoscopic gamma probe followed by fluorescence imaging (FI). In group 3, SNs were initially located via FI. Compared with group 1, in groups 2 and 3, a new tracer formulation was introduced that had a reduced total injected volume (2.0ml vs 3.2ml) but increased particle concentration. For groups 1 and 2, the Tricam SLII with D-Light C laparoscopic FI (LFI) system was used. In group 3, the LFI system was upgraded to an Image 1 HUB HD with D-Light P system. InterventionHybrid tracer-based SN biopsy, extended pelvic lymph node dissection, and robot-assisted radical prostatectomy. Outcome measurements and statistical analysisNumber and location of the preoperatively identified SNs, in vivo fluorescence-based SN identification rate, tumour status of SNs and LNs, postoperative complications, and biochemical recurrence (BCR). Results and limitationsMean fluorescence-based SN identification improved from 63.7% (group 1) to 85.2% and 93.5% for groups 2 and 3, respectively (p=0.012). No differences in postoperative complications were found. BCR occurred in three pN0 patients. ConclusionsStepwise optimisation of the hybrid tracer formulation and the LFI system led to a significant improvement in fluorescence-assisted SN identification. Preoperative SPECT-CT remained essential for guiding intraoperative SN localisation. Patient summaryIntraoperative fluorescence-based SN visualisation can be improved by enhancing the hybrid tracer formulation and laparoscopic fluorescence imaging system.

Abstract 4535: Molecular-genetic imaging of prostate cancer.

Abstract Cancer-specific promoters, such as the progression elevated gene-3 or the astrocyte elevated gene promoters, PEG-Prom and AEG-Prom, respectively, can be used as molecular genetic imaging instruments for tumor-selective imaging of cancer. We have previously shown this in experimental models of metastatic breast cancer and melanoma using bioluminescence imaging (BLI) and single photon emission computed tomography with computed tomography (SPECT/CT). Here we show that we can express PEG-Prom and AEG-Prom selectively in PC3-ML (human bone metastatic derived prostate cancer) cells and use these constructs for imaging prostate cancer in vivo. PC3-ML cells were transfected with firefly luciferase (FLuc) or the herpes simplex type I thymidine kinase (HSV1-tk), and validated for suitable transfection through bioluminescence and [125I]FIAU cell uptake assays, respectively. PC3-ML cells were administered through intra-cardiac injection to allow widespread metastases. A linear polyethyleneimine (l-PEI) nanoparticle was used for intravenous (IV) delivery of the promoter constructs to animals bearing metastases. PEG-Prom- and AEG-Prom-driven imaging reporter gene expression was monitored by small animal BLI and by SPECT/CT after IV administration of D-luciferin or [125I]FIAU, respectively. Both BLI and SPECT/CT imaging demonstrated tumor-specific PEG-Prom and AEG-Prom activity in the model of metastatic prostate cancer but not in control. Using the thoracic cavity and tibia as the regions of interest (ROI), quantification of the BLI data (n=6) at the 48 h time point after reporter gene delivery showed a range of 16- to 19-fold higher accumulation of FLuc in the metastasis group compared to control for PEG-Prom and AEG-Prom, respectively. BLI results were confirmed by histopathology, immunohistochemistry and western blot. Quantification of the SPECT/CT data (n=5) at the 56 h time point after reporter gene and 8 h after [125I]FIAU delivery showed a 3- to 11-fold higher accumulation of [125I]FIAU, depending on the tumor burden, in the group bearing metastases compared to control for AEG-Prom. Metastatic nodules detected by the SPECT/CT imaging were confirmed by pathology. The results demonstrate the potential of systemically delivered, PEG-Prom- and AEG-Prom-driven constructs for enabling the imaging of metastatic prostate cancer in vivo. Citation Format: Akrita Bhatnager, Kathleen Gabrielson, Paul B. Fisher, Martin G. Pomper. Molecular-genetic imaging of prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4535. doi:10.1158/1538-7445.AM2013-4535