99mTc Research Articles

Avoiding Full Lymphadenectomies in Intermediate- and High-Risk Endometrial Cancer by Sentinel Lymph Node Biopsy Implementation.

ObjectiveTo evaluate the role of sentinel lymph node biopsy (SLNB) to avoid staging lymphadenectomies by detecting nodal metastasis in intermediate- and high-risk endometrial cancer (EC).MethodsA single institutional retrospective study was performed including all patients with intermediate- and high-risk EC who underwent surgical nodal staging between January 2012 and December 2019. Patients with disseminated disease detected on imaging techniques or at the time of surgery were excluded. Patients were evaluable if they underwent nodal staging with SLNB and pelvic (PLD) and paraaortic (PALD) lymph node dissection. We analyzed the accuracy of the sentinel lymph node technique. Only patients with at least one sentinel lymph node (SLN) detected were included in the sensitivity and negative predictive value (NPV) analyses. The tracers used were technetium 99m, blue dye, and indocyanine green.ResultsEighty-eight patients presented intermediate- and high-risk EC (51 patients and 37 patients respectively) and underwent SLNB with consecutive PLD and PALD. The median (range) number of sentinel nodes retrieved was 2.9 (0–11). The global detection rate of SLN was 96.6% with a bilateral detection of 80.7% when considering all tracers used. However, when combination of indocyanine green and technetium was used the bilateral detection rate was 90.3%. Nodal metastases were detected in 17 (19.3%) cases, 8 (47%) of them corresponded to low volume metastasis (LVM), 7 (87.5%) of them diagnosed at ultrastaging pathologic exam. Finally, we obtained a sensitivity of 90%, a NPV of 97.5%, and a false negative rate (FNR) of 10% in the intermediate-risk EC compared to sensitivity of 85.7%, NPV of 96.6%, and FNR of 14.3% in the high-risk EC group. The only patient with isolated paraaortic nodal metastasis was found at the high-risk group, 1.1%.ConclusionsAccording to our results, full lymphadenectomy could be avoided by performing SLNB in patients with intermediate-risk EC because the only false negative case detected was at the beginning of ICG learning curve. For high-risk EC patients we did not find enough evidence to support the systematic avoidance of staging full lymph node dissection. Nevertheless, SLNB should be performed in all cases of EC as it improves LVM diagnosis substantially.

Comparison of Renal Ultrasonography and Technetium 99-M Dimercaptosuccinic acid Renal Cortical Scintigraphy in Identifying Renal Parenchymal Defects in Febrile Urinary Tract Infection In Children Less than Five Years Age

Comparison of Renal Ultrasonography and Technetium 99-M Dimercaptosuccinic acid Renal Cortical Scintigraphy in Identifying Renal Parenchymal Defects in Febrile Urinary Tract Infection In Children Less than Five Years Age

Experimental evaluation of the GE NM/CT 870 CZT clinical SPECT system equipped with WEHR and MEHRS collimator.

PurposeA high‐energy‐resolution whole‐body SPECT‐CT device (NM/CT 870 CZT; C‐SPECT) equipped with a CZT detector has been developed and is being used clinically. A MEHRS collimator has also been developed recently, with an expected improvement in imaging accuracy using medium‐energy radionuclides. The objective of this study was to compare and analyze the accuracies of the following devices: a WEHR collimator and the MEHRS collimator installed on a C‐SPECT, and a NaI scintillation detector‐equipped Anger‐type SPECT (A‐SPECT) scanner, with a LEHR and LMEGP.MethodsA line phantom was used to measure the energy resolutions including collimator characteristics in the planar acquisition of each device using 99mTc and 123I. We also measured the system's sensitivity and high‐contrast resolution using a lead bar phantom. We evaluated SPECT spatial resolution, high‐contrast resolution, radioactivity concentration linearity, and homogeneity, using a basic performance evaluation phantom. In addition, the effect of scatter correction was evaluated by varying the sub window (SW) employed for scattering correction.ResultsThe energy resolution with 99mTc was 5.6% in C‐SPECT with WEHR and 9.9% in A‐SPECT with LEHR. Using 123I, the results were 9.1% in C‐SPECT with WEHR, 5.5% in C‐SPECT with MEHRS, and 10.4% in A‐SPECT with LMEGP. The planar spatial resolution was similar under all conditions, but C‐SPECT performed better in SPECT acquisition. High‐contrast resolution was improved in C‐SPECT under planar condition and SPECT. The sensitivity and homogeneity were improved by setting the SW for scattering correction to 3% of the main peak in C‐SPECT.ConclusionC‐SPECT demonstrates excellent energy resolution and improved high‐contrast resolution for each radionuclide. In addition, when using 123I, careful attention should be paid to SW for scatter correction. By setting the appropriate SW, C‐SPECT with MEHRS has an excellent scattered ray removal effect, and highly homogenous imaging is possible while maintaining the high‐contrast resolution.

Reducing scan time of paediatric 99mTc-DMSA SPECT via deep learning

To investigate the feasibility of reducing the scan time of paediatric technetium 99m (99mTc) dimercaptosuccinic acid (DMSA) single-photon-emission computed tomographic (SPECT) using a deep learning (DL) method. A total of 112 paediatric 99mTc-DMSA renal SPECT scans were analysed retrospectively. Of the 112 examinations, 88 (84 for training and four for validation) were used to train a DL-based model that could generate full-acquisition-time reconstructed SPECT images from half-time acquisition. The remaining 24 examinations were used to evaluate the performance of the trained model. DL-based SPECT images obtained from half-time acquisition have image quality similar to the standard clinical SPECT images obtained from full-acquisition-time acquisition. Moreover, the accuracy, sensitivity and specificity of the DL-based SPECT images for detection of affected kidneys were 91.7%, 83.3%, and 100%, respectively. These preliminary results suggest that DL has the potential to reduce the scan time of paediatric 99mTc-DMSA SPECT imaging while maintaining diagnostic accuracy.

Status of Sentinel Lymph Node Biopsy in Vulvar and Cervical Cancer.

Assessment of lymphatic metastasis is an essential component of solid tumour staging. Sentinel lymph node (SLN) biopsy is a minimally invasive procedure that allows regional lymph node involvement by tumour to be estimated by selectively examining the sentinel lymph node while minimising the morbidity of systematic lymph node dissection. Within the group of genital cancers, the diagnostic value of SLN biopsy is rated differently. For selected patients with early-stage vulvar cancer (unifocal primary tumour < 4 cm, clinically negative inguinal lymph nodes) the SLN technique is already an established procedure in the guidelines of the German Society for Gynaecology and Obstetrics (DGGG)/German Cancer Society (DKG) and the recommendations of the European Society of Gynaecological Oncology (ESGO). For cervical cancer, SLN biopsy has not yet been sufficiently standardised but can be considered for patients without risk factors with a primary tumour size < 2 cm. The SLN is identified by combined use of radioactive 99m technetium nanocolloid and patent blue. The use of indocyanine green offers an alternative for SLN identification with few side effects. Recent studies aim to increase the diagnostic reliability of intraoperative frozen section analysis as this continues to show limited sensitivity in both vulvar and cervical cancer. The rate of detection of micrometastases can be increased by additional ultrastaging, the prognostic significance of which for both diseases is still unclear. The prognostic value of SLN biopsy compared with systematic lymph node dissection is being investigated in current studies (GROINSS-V-II for vulvar cancer and SENTIX-, SENTICOL-3 for cervical cancer). For this review article, a guideline-based literature search was performed in the National Library of Medicine (PubMed/MEDLINE) database with a particular focus on recent cohort studies and conference contributions.

Worldwide Diagnostic Reference Levels for Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging: Findings From INCAPS

ObjectivesThis study sought to establish worldwide and regional diagnostic reference levels (DRLs) and achievable administered activities (AAAs) for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). BackgroundReference levels serve as radiation dose benchmarks to compare individual laboratories against aggregated data, helping to identify sites in greatest need of dose reduction interventions. DRLs for SPECT MPI have previously been derived from national or regional registries. To date there have been no multiregional reports of DRLs for SPECT MPI from a single standardized dataset. MethodsData were submitted voluntarily to the INCAPS (International Atomic Energy Agency Nuclear Cardiology Protocols Study), a cross-sectional, multinational registry of MPI protocols. A total of 7,103 studies were included. DRLs and AAAs were calculated by protocol for each world region and for aggregated worldwide data. ResultsThe aggregated worldwide DRLs for rest-stress or stress-rest studies employing technetium Tc 99m–labeled radiopharmaceuticals were 11.2 mCi (first dose) and 32.0 mCi (second dose) for 1-day protocols, and 23.0 mCi (first dose) and 24.0 mCi (second dose) for multiday protocols. Corresponding AAAs were 10.1 mCi (first dose) and 28.0 mCi (second dose) for 1-day protocols, and 17.8 mCi (first dose) and 18.7 mCi (second dose) for multiday protocols. For stress-only technetium Tc 99m studies, the worldwide DRL and AAA were 18.0 mCi and 12.5 mCi, respectively. Stress-first imaging was used in 26% to 92% of regional studies except in North America where it was used in just 7% of cases. Significant differences in DRLs and AAAs were observed between regions. ConclusionsThis study reports reference levels for SPECT MPI for each major world region from one of the largest international registries of clinical MPI studies. Regional DRLs may be useful in establishing or revising guidelines or simply comparing individual laboratory protocols to regional trends. Organizations should continue to focus on establishing standardized reporting methods to improve the validity and comparability of regional DRLs.

Long-term renal function after treatment for unilateral, nonsyndromic Wilms tumor. A report from the St. Jude Lifetime Cohort Study.

The impact of specific treatment modalities on long-term renal function and blood pressure among adult survivors of Wilms tumor (WT) has not been well documented. Among 40 WT survivors and 35 noncancer controls, we estimated the glomerular filtration rate (eGFR) using the Chronic Kidney Disease-Epidemiology (CKD-EPI) equations with and without cystatin C, obtained 24-hour ambulatory blood pressure readings, and, among survivors only, measured 99m Tc diethylenetriamine pentaacetic acid (DTPA) plasma clearance. Survivors were treated with unilateral nephrectomy and nonnephrotoxic chemotherapy. Twenty received whole abdomen radiation therapy (WART) [median -16.5 Gray (Gy)], and 20 received no radiation therapy. Pairwise comparisons between survivors treated with and without WART, and each group to controls were performed using two-sample t tests. Twenty-six (65%) WT survivors were female, and 33 (83%) were non-Hispanic white. GFR estimated with creatinine or creatinine + cystatin C was decreased among irradiated survivors compared with controls. No irradiated or unirradiated participant had an eGFR (creatinine + cystatin C)<60mL/min/1.73m2 . The prevalence of hypertension was significantly increased among unirradiated (25%) and irradiated survivors (35%) compared with controls (0%). Of the 24-hour ambulatory blood pressure monitoring parameters evaluated, only mean sleep period diastolic blood pressure load of those who received WART was significantly different from that of controls. Chronic kidney disease was infrequent in long-term survivors of unilateral nonsyndromic WT, whether treated with WART or no radiation. The prevalence of hypertension was increased in both groups compared with controls, emphasizing the need for ongoing monitoring of renal and cardiovascular health.

99m Tc-(EDDA/tricine)-HYNIC-GnRH analogue as a potential imaging probe for diagnosis of prostate cancer.

Prostate cancer is a serious threat to men's health, so it is necessary to develop the techniques for early detection of this malignancy. Radiolabeled peptides are the useful tools for diagnosis of prostate cancer. In this research, we designed a new HYNIC-conjugated GnRH analogue and labeled it by 99m Tc with tricine/EDDA as coligands. We used aminohexanoic acid (Ahx) as a hydrocarbon linker to generate 99m Tc-(tricine/EDDA)-HYNIC-Ahx-[DLys6 ]GnRH. The radiopeptide exhibited high radiochemical purity and stability in solution and serum. Two human prostate cancer cell lines LN-CaP and DU-145 were used for cellular experiments. The binding specificity and affinity of radiopeptide for LN-CaP were superior to DU-145 cells. The Kd values for LN-CaP and DU-145 cells were 41.91±7.03nM and 55.96±10.56nM, respectively. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor/muscle ratio of 99m Tc-HYNIC-Ahx-[DLys6 ]GnRH was 4.14 at 1hr p.i. that decreased to 2.41 at 4hr p.i. in LN-CaP tumor-xenografted nude mice. The blocking experiment revealed that the tumor uptake was receptor-mediated. The lesion was visualized clearly using 99m Tc-[DLys6 ]GnRH at 1hr p.i. Accordingly, this research highlights the capability of 99m Tc-(tricine/EDDA)-HYNIC-Ahx-[DLys6 ]GnRH peptide as a promising agent for GnRHR-expressing tumor imaging.

Maximizing Deep Lung Deposition in Healthy and Fibrotic Subjects During Jet Nebulization.

Background: In volunteers with idiopathic pulmonary fibrosis (IPF), inhaled Interferon-γ (IFN-γ) is safe and may improve pulmonary function. However, coughing, associated with upper airway deposition, is often reported. To address this problem, a small-particle, breath-enhanced jet nebulizer (i-NEB Mini; InspiRx, Inc., Somerset, NJ) was developed. Using gamma scintigraphy, this device was tested in healthy individuals and subjects with IPF to determine efficiency and regional deposition in lung and airways.Methods: Four healthy individuals and nine subjects with IPF were enrolled. The nebulizer was filled with 2 mL of saline with 99m Tc bound to diethylenetriaminepentaacetic acid (DTPA) powered continuously with 3.4 L/min of compressed air. Mass median aerodynamic diameter (MMAD) was measured by cascade impactor. To maximize deposition in alveoli, inspiratory flow was limited by an inspiratory resistance incorporated into the nebulizer, resulting in a deep inspiration ∼6 seconds. The treatment was run to completion (10 minutes), and each subject underwent deposition imaging. Mass balance and regions of interest determined upper airway (measured by calibrated stomach activity) and regional lung deposition as a percent of pretreatment nebulizer charge.Results: Subjects tolerated the device with no complaints. MMAD (mean [geometric standard deviation]) = 1.04 [1.92] μm. Lung deposition (mean ± standard error, % nebulizer charge) in healthy subjects was 26.2% ± 1.83 and in IPF individuals 23.4% ± 1.60 (p = 0.414). Upper airway deposition was 1.4% ± 0.83 and 2.3% ± 0.48, respectively (p = 0.351), and 20.1% was lost during expiration. Central/Peripheral ratios were consistent in both groups, showing high peripheral deposition (1.32 ± 0.050, vs. 1.28 ± 0.046, p = 0.912).Conclusion: The i-NEB Mini jet nebulizer with breath enhancement produced small particles, resulting in minimal upper airway deposition. Using slow and deep breathing, more than half of the emitted dose deposited in the peripheral lung in normal subjects and individuals with IPF. These data indicate that, for future clinical trials, controlled lung doses of small particles, designed to avoid coughing, are possible even in subjects with advanced disease.

Thyrotropin-secreting adenoma in multiple endocrine neoplasia type 1: one case report and literature review

Objective To improve the understanding of thyrotropin-secreting adenoma in multiple endocrine neoplasia type 1(MEN1) through analyzing the clinical diagnosis and treatment process, as well as outcomes in one case of this disorder. Methods The clinical manifestations, biochemical and hormone levels, imaging presentations, medical and surgical treatments, and post-operational pathologic findings in the process of diagnosis and treatment of a patient with thyrotropin-secreting adenoma in MEN1 were analyzed. The next generation sequencing followed by Sanger method was used for analyzing MEN1 and related genes. The results were evaluated with online PolyPhen2 and PROVEAN for variation hazard. Results One 19-year old male patient was diagnosed with hyperthyroidism due to thyrotoxicosis and high level of thyroid hormones(THs) with measurable TSH(2.78 mIU/L) and negative thyrotropin receptor antibody(TRAb). Meanwhile, primary hyperparathyroidism was suggested by hypercalcemia, hypophosphatemia, and elevated intact parathyroid hormone(PTH) level, all the parameters were returned to normal after surgical resection of the mass which was below the left thyroid lobe indicated by ultrasound and 99mTc scan. Thyrotoxicosis remained in spite of one year treatment with antithyroid drug, thyrotropinoma was then suspected, and subsequent MRI scan found a macroadenoma at right pituitary. TSH and THs returned to normal 1 month after transsphenoidal removal of the adenoma. As expected, immunohistochemical staining revealed TSH positive. In addition, a pancreatic mass was found by both CT and MRI scan, which was considered as a silent neuroendocrine tumor. Gene analysis revealed a missense mutation of MEN1 as c. 415C>T and p. His139Tyr(H139Y), which was predicted highly hazard. Only five cases of thyrotropinoma in MEN1 were previously reported. Conclusion Thyrotropinoma should be cautiously identified from hyperthyroidism to avoid misdiagnosis and mistreatment, and it should keep in mind that thyrotropinoma may be associated with MEN1 though it would be very rare. Key words: Thyrotropinoma; Multiple endocrine neoplasia type 1; Hyperthyroidism; Hyperparathyroidism; MEN1 gene; Silent pancreatic neuroendocrine tumor

Discordance in the distributions of anatomical liver volume and the liver function measured on scintigraphy in the future liver remnant using 99m Technetium -Mebrofinate SPECT-CT scan

Background: Preoperative evaluation of future liver remnant (FLR) is traditionally assessed using standardised anatomical liver volumes to prevent post-hepatectomy liver failure. 99m Technetium -Mebrofinate scan is emerging as a promising pre-operative investigation to assess the global, lobar and the dynamic liver function. With a combination of 99m Technetium -Mebrofinate and SPECT-CT anatomical liver volumes can also be assessed. Aim: The study is aimed to investigate if there is a difference in the percentage distribution of scintigraphy within the given anatomical volume of the planned future liver remnant. Methods: All patients who underwent 99m Tc-Mebrofenin SPECT-CT scan in the unit since 2018 were included. Data were processed on a workstation (MultiModality; Hermes Medical Solutions) to assess the anatomical volumes, global liver function and lobar liver function assessed as scintigraphy as well as dynamic liver function. Data was collated from a prospectively maintained database. Results: Fifty-two 99m Tc-Mebrofenin SPECT-CT scans were included of which three patients had the scan prior to the second stage liver resection. Nine scans during the initial learning curve where all the above parameters were not assessed were excluded. Median global sum count was 8257858/voxel. Median global dynamic uptake /min was 12.35 (4.66-20.85). Median anatomical remnant volume was 506ml (range: 312-1453ml). Percentages of the anatomical remnant volume vs functional distribution were shown in Figure 1 (r=0.69; p<0.001). There was a no variation in 7/43 scans (16.2%), up to 5% variation in 24 scans (55.8%), between 5 and 10% variation in 5 scans (11.4%), and of more than 10% in 7/ 43 patients (16.2%) Conclusion: Based on the non-homogeneous distribution of liver function, we recommend functional imaging (99m Tc-Mebrofenin SPECT-CT or equivalent) to be included in the pre-operative assessment of patients undergoing major liver resections.

New, Unconfirmed Bone Lesions in Prostate Cancer Patients Receiving Enzalutamide

Technetium 99m bone scans remain the primary diagnostic imaging test to assess bone metastases in patients with advanced prostate cancer. However, use

To Sandwich Technetium: Highly Functionalized Bis-Arene Complexes [99m Tc(η6 -arene)2 ]+ Directly from Water and [99m TcO4

The labeling of (bio)molecules with metallic radionuclides such as 99m Tc demands conjugated, multidentate chelators. However, this is not always necessary since phenyl rings can directly serve as integrated, organometallic ligands. Bis-arene sandwich complexes are generally prepared by the Fischer-Hafner reaction. In extension of this, we show that [99m Tc(η6 -C6 R6 )2 ]+ -type complexes are directly accessible from water and [99m TcO4 ]- , even using arenes incompatible with Fischer-Hafner conditions. To unambiguously confirm the nature of these unprecedented 99m Tc complexes, their rhenium homologous have been prepared by substituting naphthalene ligands in [Re(η6 -C10 H8 )2 ]+ with the corresponding phenyl groups. The ease with which highly stable [99m Tc(η6 -C6 R6 )2 ]+ complexes are formed under standard labeling conditions enables a multitude of new potential imaging agents based on commercial pharmaceuticals or lead structures.

Radiolabeling and in vitro evaluation of a new 5‐fluorouracil derivative with cell culture studies

The clinical impact and accessibility of 99m Tc tracers for cancer diagnosis would be greatly enhanced by the availability of a new, simple, and easy labeling process and radiopharmaceuticals. 5-Fluorouracil is an antitumor drug, which has played an important role for the treatment of breast carcinoma. In the present study, a new derivative of 5-Fluorouracil was synthesized as (1-[{1'-(1''-deoxy-2'',3'':4'',5''-di-O-isopropylidene-β-D-fructopyranose-1''-yl)-1'H-1',2', 3'-triazol-4'-yl}methyl]-5-fluorouracil) (E) and radiolabeled with 99m Tc. It was analyzed by radio thin layer chromatography for quality control and stability. The radiolabeled complex was subjected to in vitro cell-binding studies to determine healthy and cancer cell affinity using HaCaT and MCF-7 cells, respectively. In addition, in vitro cytotoxicity studies of compound E were performed with HaCaT and MCF-5 cells. The radiochemical purity of the [99m Tc]TcE was found to be higher than 90% at room temperature up to 6 hours. The radiolabeled complex showed higher specific binding to MCF-7 cells than HaCaT cells. IC50 values of E were found 31.5 ± 3.4 μM and 20.7 ± 2.77 μM for MCF-7 and HaCaT cells, respectively. The results demonstrated the potential of a new radiolabeled E with 99m Tc has selective for breast cancer cells.

2578 Meckel's Diverticulum: A Diverticulum Like No Other

INTRODUCTION: Meckel's diverticulum (MD) is a relatively uncommon cause of gastrointestinal (GI) bleeding in adults. “Often looked for and seldom found,” MD is challenging to diagnose despite the various imaging modalities available. Herein, we present the case of a young man who presented with lower GI hemorrhage and negative endoscopy, bleeding scan, and angiography. Meckel's diverticulum was later diagnosed via scintigraphy scan. We review the noninvasive diagnostic imaging for Meckel's diverticulum, mainly technetium-99m (Tc 99m) pertechnetate scan, and bleeding scan. CASE DESCRIPTION/METHODS: A 26-year-old man presented with multiple episodes of melena. He had acute onset anemia. Workup, including upper endoscopy, colonoscopy, and push enteroscopy were not able to identify the site of bleeding even after repeat procedures. A computed tomography scan with intravenous contrast and mesenteric angiography were also unrevealing. A Technetium 99m bleeding scan was read as negative. Persistent bleeding necessitated recurrent transfusions. Capsule endoscopy was deployed. A Meckel's scan (Tc 99m Pertechnetate scan) revealed an abnormal focus of uptake in the right lower abdomen suggesting the diagnosis of Meckel's diverticulum. The patient underwent laparoscopic resection of the diverticulum and was discharged home (Figures 1 and 2). A retrospective review of the bleeding scan revealed isolated uptake in the location of the Meckel's Diverticulum. Review of the capsule endoscopy revealed a diverticulum in the small bowel in the right lower quadrant without active bleeding (Figure 3). DISCUSSION: Bleeding Meckel's diverticulum is easier to diagnose than MD presenting with other symptoms, but still an outstanding challenge. High suspicion for MD should be sought in the evaluation of a young patient presenting with GI bleeding; the gold standard for diagnosis is the technetium-99m pertechnetate scan or so-called Meckel's scan. Bleeding scan is another noninvasive imaging modality that helps to detect a bleeding MD. Although both scans use Tc 99m, the mechanism is different. Meckel's scan uses Tc 99m, which is secreted by parietal cells in the mucus, thus detecting gastric cells within MD. On the other hand, the bleeding scan works via identifying Tc 99m that is bound to hemoglobin, therefore identifying a bleeding MD. Both scans are noninvasive and safe. The use of either one should be tailored according to the clinical presentation.

Assessment of Nonradioactive Multispectral Optoacoustic Tomographic Imaging With Conventional Lymphoscintigraphic Imaging for Sentinel Lymph Node Biopsy in Melanoma

The metastatic status of sentinel lymph nodes (SLNs) is the most relevant prognostic factor in breast cancer, melanoma, and other tumors. The conventional standard to label SLNs is lymphoscintigraphy with technetium Tc 99m. A worldwide shortage and known disadvantages of Tc 99m have intensified efforts to establish alternative, nonradioactive imaging techniques. To assess a new nonradioactive method using multispectral optoacoustic tomographic (MSOT) imaging in comparison with conventional lymphoscintigraphic imaging for SLN biopsy (SLNB) in melanoma. Analysis of a cross-sectional study was conducted at the University Hospital-Essen, Skin Cancer Center, Essen, Germany. Between June 2, 2014, and February 22, 2019, 83 patients underwent SLNB with an additional preoperative indocyanine green (ICG) application. Sentinel lymph node basins were preoperatively identified by MSOT imaging, and ICG-labeled SLNs were intraoperatively detected using a near-infrared camera. The surgeons were blinded to the lymphoscintigraphic imaging results in the beginning of the SLNB. Use of a γ probe was restricted until the SLNB procedure was attempted by the nonradioactive method. Concordance of SLN basins and SLNs identified by MSOT imaging plus near-infrared camera vs lymphoscintigraphic imaging plus single-photon emission computed tomographic or computed tomographic imaging was assessed. Of the 83 patients (mean [SD] age, 54.61 [17.53] years), 47 (56.6%) were men. In 83 surgical procedures, 165 SLNs were excised. The concordance rate of ICG-labeled and Tc 99m-marked detected SLN basins was 94.6% (n = 106 of 112). Intraoperatively, 159 SLNs were detected using a near-infrared camera and 165 were detected by a γ probe, resulting in a concordance rate of 96.4%. Multispectral optoacoustic tomographic imaging visualized SLNs in all anatomic regions with high penetration depth (5 cm). The findings of this study suggest that nonradioactive SLN detection via MSOT imaging allows identification of SLNs at a frequency equivalent to that of the current radiotracer conventional standard. Multispectral optoacoustic tomographic imaging appears to be a viable nonradioactive alternative to detect SLNs in malignant tumors.

Sentinel lymph node fingerprinting

Background. When locating the sentinel lymph node (SLN), surgeons use state-of-the-art imaging devices, such as a 1D gamma probe or less widely spread a 2D gamma camera. These devices project the 3D subspace onto a 1D respectively 2D space, hence loosing accuracy and the depth of the SLN which is very important, especially in the head and neck area with many critical structures in close vicinity. Recent methods which use a multi-pinhole collimator and a single gamma detector image try to gain a depth estimation of the SLN. The low intensity of the sources together with the computational cost of the optimization process make the reconstruction in real-time, however, very challenging.Results. In this paper, we use an optimal design approach to improve the classical pinhole design, resulting in a non-symmetric distribution of the pinholes of the collimator. This new design shows a great improvement of the accuracy when reconstructing the position and depth of the radioactive tracer. Then, we introduce our Sentinel lymph node fingerprinting (SLNF) algorithm, inspired by MR-fingerprinting, for fast and accurate reconstruction of the tracer distribution in 3D space using a single gamma detector image. As a further advantage, the method requires no pre-processing, i.e. filtering of the detector image. The method is very stable in its performance even for low exposure times. In our ex vivo experiments, we successfully located multiple Technetium 99m (Tc-99m) sources with an exposure time of only one second and still, with a very small L2-error.Conclusion. These promising results under short exposure time are very encouraging for SLN biopsy. Although, this device has not been tested on patients yet, we believe: that this approach will give the surgeon accurate 3D positions of the SLN and hence, can potentially reduce the trauma for the patient.

Effect of excessive iodine intake on the 99Tcm-pertechnetate uptake function of thyroid and the related mechanism

Objective To study the influence of excessive iodine intake on the 99Tcm-pertechnetate uptake function of thyroid and explore the related mechanism. Methods A total of 150 male Wistar rats were divided into normal iodine group (NI group) and 4 high iodine (HI) groups (10HI, 50HI, 100HI and 500HI group) with completely random method. Each group included 30 rats. Rats in HI groups were intragastrically administrated with different concentrations of KIO3, and rats in NI group were administrated with the same amount of distilled water. After a 7 d HI diet, each group was randomly divided into 3 subgroups: 7 d group (HI diet for 7 d), 10 d group (HI diet for 7 d + limiting iodine for 3 d) and 14 d group (HI diet for 7 d + limiting iodine for 7 d). All rats were given 1.85 MBq 99TcmO4-, then the thyroid glands were isolated and weighed 20 min post-injection. The radioactive counts were measured and the thyroid uptake percentage activity of injected dose per gram of tissue (%ID/g) of 99TcmO4- for each sample was calculated. Sodium-iodide symporter (NIS) expression level was analyzed by Western blot. One-way analysis of variance or Welch test was used to compare the differences among groups, and Spearman rank correlation analysis was also used. Results At the same observation time, the %ID/g of 99TcmO4- and NIS expression among different HI groups were statistically significant (F values: 48.825-119.219, all P 0.05). Significant differences of %ID/g of 99TcmO4- and NIS expression were found among different time subgroups in 50HI, 100HI and 500HI groups (F values: 10.442-90.408, all P<0.01). Spearman correlation analysis showed that the concentration of iodine correlated negatively with %ID/g of 99TcmO4- and NIS expression (rs values: -0.853 and -0.950, both P<0.01), while the %ID/g of 99TcmO4- and NIS expression was positively correlated (rs=0.925, P<0.01). Conclusions Excessive iodine intake can inhibit thyroid uptake of 99TcmO4- in rats, which is associated with the down-regulation of NIS expression. The degree of inhibition correlates positively with iodine concentration, and correlates negatively with NIS expression. The degree of recovery of NIS and %ID/g of 99TcmO4- may relate to the time of limiting the iodine intake. Key words: Thyroid gland; Sodium pertechnetate Tc 99m; Iodine; Rats; Sodium/iodide symporter

New 99m Tc(CO)3 -radiolabeled arylpiperazine pharmacophore as potent 5HT1A serotonin receptor radiotracer: Docking studies, chemical synthesis, radiolabeling, and biological evaluation.

In spite of previous efforts, there is lack of a radiotracer for imaging the 5HT1A receptor density in human brain, which is involved in several neurological brain disorders. The aim of this study was to prepare a new derivative of 1-(2-methoxyphenyl)piperazine (MPP) as a main chemical structure of 5HT1A receptor antagonist with 3-carbon linker and radiolabeled by [99m Tc][Tc(CO)3 (H2 O)3 ]+ precursor. Docking studies before chemical synthesis showed similar fashion of interaction for both WAY100635 (potent 5HT1A receptor antagonist) and new designed ligand, despite of addition of 99m Tc(CO)3 group in the structure of new ligand. MPP-(CH2 )3 -N3 was synthesized via three efficient and reliable chemical synthesis steps (more than 80% yield) then radiolabeled by addition of 2-ethynylpyridine and [99m Tc][Tc(CO)3 (H2 O)3 ]+ precursor in one pot procedure (more than 95% radiochemical efficiency) through click chemistry method. After incubation, radiotracer was found stable in vitro up to 2hours. Binding assays showed about 33% specific binding of radiotracer to the 5HT1A receptors. Brain biodistribution studies indicated (0.26±0.05)% ID/g hippocampus uptake at 30minutes post injection, which its specificity was verified through blocking studies. These results suggested that new designed radioligand might serve as a potent SPECT imaging agent to estimate status of 5HT1A receptors.

Internal radiation dose assessment of radiopharmaceuticals prepared with cyclotron-produced 99m Tc.

Technetium-99m (99m Tc) is the radioisotope most widely used in diagnostic nuclear medicine. It is readily available from 99 Mo/99m Tc generators as the β- decay product of the 99 Mo (T&frac12; =66h) parent nuclide. This latter is obtained as a fission product in nuclear reactors by neutron-induced reactions on highly enriched uranium. Alternative production routes, such as direct reactions using proton beams on specific target materials [100 Mo(p,2n)99m Tc], have the potential to be both reliable and relatively cost-effective. However, results showed that the 99m Tc extracted from proton-bombarded 100 Mo-enriched targets contains small quantities of several Tc radioisotopes (93m Tc, 93 Tc, 94 Tc, 94m Tc, 95 Tc, 95m Tc, 96 Tc, and 97m Tc). The aim of this work was to estimate the dose increase (DI) due to the contribution of Tc radioisotopes generated as impurities, after the intravenous injection of four radiopharmaceuticals prepared with cyclotron-produced 99m Tc (CP-99m Tc) using 99.05% 100 Mo-enriched metallic targets. Four 99m Tc radiopharmaceuticals (pertechnetate, sestamibi (MIBI), hexamethylpropylene-amine oxime (HMPAO) and disodium etidronate (HEDP)) were considered in this study. The biokinetic models reported by the International Commission on Radiological Protection (ICRP) for each radiopharmaceutical were used to define the main source organs and to calculate the number of disintegrations per MBq that occurred in each source organ (Nsource ) for each Tc radioisotope present in the CP-99m Tc solution. Then, target organ equivalent doses and effective dose were calculated for each Tc radioisotope with the OLINDA/EXM software versions 1.1 and 2.0, using the calculated Nsource values and the adult male phantom as program inputs. Total effective dose produced by all Tc isotopes impurities present in the CP-99m Tc solution was calculated using the fraction of total activity corresponding to each radioisotope and compared with the effective dose delivered by the generator-produced 99m Tc. In all cases, the total effective DI of CP-99m Tc radiopharmaceuticals calculated with either versions of the OLINDA software was less than 10% from 6 up to 12h after EOB. 94m Tc and 93m Tc are the Tc radioisotopes with the highest concentration in the CP-99m Tc solution at EOB. However, their contribution to DI 6h after EOB is minimal, due to their short half-lives. The radioisotopes with the largest contribution to the effective DI are 96 Tc, followed by 95 Tc and 94 Tc. This is due to the types of their emissions and relatively long half-lives, although their concentration in the CP-99m Tc solution is five times lower than that of 94m Tc and 93m Tc at the EOB. The increase in the radiation dose caused by other Tc radioisotopes contained in CP-99m Tc produced as described here is quite low. Even though the concentrations of the 94 Tc and 95 Tc radioisotopes in the CP-99m Tc solution exceed the limits established by the European Pharmacopoeia, CP-99m Tc radiopharmaceuticals could be used in routine nuclear medicine diagnostic studies if administered from 6 to 12h after the EOB, thus maintaining the effective DI within the 10% limit.