Corticobasal syndrome mimicking Foix-Chavany-Marie syndrome with suggested 4-repeat tauopathy by tau PET.

BACKGROUND: Corticobasal syndrome (CBS) is a neurodegenerative disease diagnosed based on clinical manifestations such as asymmetrical parkinsonism, limb apraxia, and speech and language impairment. The background pathology of CBS is commonly a variety of proteinopathies, but association with cerebrovascular disease has also been reported. Foix-Chavany-Marie syndrome (FCMS) is a rare neurological disorder characterized by facio-pharyngo-glossal diplegia with automatic-voluntary movement dissociation presenting with bilateral paresis of the facial, lingual, pharyngeal and masticatory muscles. FCMS is commonly attributable to stroke. Transactive response DNA binding protein of 43 kD (TDP-43) proteinopathy is also known as the pathological background of FCMS, while the pathological background of the majority of CBS cases consists of diverse tauopathies instead of TDP-43 proteinopathy. In this report, we describe a case mimicking FCMS that was finally diagnosed as CBS with suggested 4-repeat tauopathy. CASE PRESENTATION: A 68-year-old female started experiencing difficulty speaking followed by difficulty writing, and especially texting, several years before her visit. Her impairment had been gradually worsening, and she came to our hospital. On neurological examination, she demonstrated the facial apraxia, frontal lobe dysfunction, and upper motor neuron signs. She presented some characteristics suggestive of FCMS. Her symptoms exhibited rapid progression and myoclonus, parkinsonism, and left-side dominant cortical sensory deficit occurred, resulting in the fulfillment of diagnostic criteria for CBS after 9 months. Tau PET imaging displayed notable ligand uptake in the brainstem, subthalamic nuclei, basal ganglia, and bilateral subcortical frontal lobe, suggesting that her pathological background was 4-repeat tauopathy. As a result of her progressive dysphagia, she became unable to eat and passed away after 12 months. CONCLUSION: We hereby present an atypical case of CBS showing clinical features mimicking FCMS at first presentation. TDP-43 proteinopathy was suspected based on the clinical symptoms in the early stages of the disease; however, the clinical course and imaging findings including tau PET suggested that her pathological background was 4-repeat tauopathy.

Relationship between laparoscopic total gastrectomy-associated postoperative complications and gastric cancer prognosis.

This study aimed to investigate the incidence and prognosis of postoperative complications after laparoscopic total gastrectomy (LTG) for gastric cancer (GC). We retrospectively enrolled 411 patients who underwent curative LTG for GC at seven institutions between January 2004 and December 2018. The patients were divided into two groups, complication group (CG) and non-complication group (non-CG), depending on the presence of serious postoperative complications (Clavien-Dindo grade III [≥ CD IIIa] or higher complications). Short-term outcomes and prognoses were compared between two groups. Serious postoperative complications occurred in 65 (15.8%) patients. No significant difference was observed between the two groups in the median operative time, intraoperative blood loss, number of lymph nodes harvested, or pathological stage; however, the 5-year overall survival (OS; CG 66.4% vs. non-CG 76.8%; p = 0.001), disease-specific survival (DSS; CG 70.1% vs. non-CG 76.2%; p = 0.011), and disease-free survival (CG 70.9% vs. non-CG 80.9%; p = 0.001) were significantly different. The Cox multivariate analysis identified the serious postoperative complications as independent risk factors for 5-year OS (HR 2.143, 95% CI 1.165-3.944, p = 0.014) and DSS (HR 2.467, 95% CI 1.223-4.975, p = 0.011). A significant difference was detected in the median days until postoperative recurrence (CG 223 days vs. non-CG 469 days; p = 0.017) between the two groups. Serious postoperative complications after LTG negatively affected the GC prognosis. Efforts to decrease incidences of serious complications should be made that may help in better prognosis in patients with GC after LTG.

Synthesis and Preliminary Evaluation of an 18F-labeled Oleate Analog to Image Fatty Acid Beta-Oxidation in the Absence of Metabolic Defluorination.

PURPOSE: Fatty acid oxidation (FAO) is a key parameter for evaluating cardiovascular, oncologic, neurologic, and other metabolic diseases. Several single-photon emission computed tomography and positron emission tomography (PET) tracers have been developed to measure FAO. Among these, 18-[18F]fluoro-4-thia-oleate ([18F]FTO), first developed by DeGrado et al., is well characterized. Here, we synthesized several analogs of [18F]FTO to improve the metabolic stability of the C-18F bond, and preliminarily evaluated their performance in monkey PET studies. PROCEDURES: Several secondary 18F-fluorinated analogs, 17-[18F]fluoro-4-thia-oleate (17-[18F]FTO), 15-[18F]fluoro-4-thia-oleate (15-[18F]FTO), 12-[18F]fluoro-4-thia-oleate (12-[18F]FTO), 7-[18F]fluoro-4-thia-oleate, (7-[18F]FTO, [18F]AS3504073-00), and 6-[18F]fluoro-4-thia-oleate (6-[18F]FTO), were synthesized from tosylate or bromide precursors using similar procedures. Nucleophilic 18F fluorination on each precursor was performed using [18F]tetrabutylammonium fluoride/tetrabutylammonium hydrocarbonate, followed by hydrolysis of methylester. All synthesized 18F-labeled compounds were administered to cynomolgus monkeys, and PET measurements were performed. From the monkey PET studies, 7-[18F]FTO was selected as the best tracer and used to perform preliminary evaluations in mice. RESULTS: All five compounds had sufficient quality and stability for animal experiments. In monkey PET studies, 12-, 7-, and 6-[18F]FTO showed greater accumulation in the heart than [18F]FTO, but not 17- and 15-[18F]FTO. Only 7-[18F]FTO did not show significant accumulation in the bone. The standardized uptake values (SUVs) for 12-[18F]FTO, 7-[18F]FTO, and 6-[18F]FTO were 9.77, 9.26, and 7.25 in the heart, and 3.17, n.d., and 1.96 in the bone 1 h after administration, respectively. In mouse distribution studies, SUVs 1 h after administration of 7-[18F]FTO and [18F]FTO were 10.4 and 10.0 in the heart, and 0.37 and 3.48 in the femur, respectively. Administration of etomoxir, a carnitine palmitoyltransferase inhibitor, reduced SUVs of 7-[18F]FTO and [18F]FTO in the heart by 91% and 87%, respectively. CONCLUSIONS: We developed a novel PET tracer 7-[18F]FTO/[18F]AS3504073-00 for FAO imaging. 7-[18F]FTO had an excellent PET tracer profile, suggesting it may be a useful tracer for FAO imaging. Further evaluations of the tracer are ongoing.

Outcomes of laparoscopic total gastrectomy in elderly patients: a propensity score matching analysis.

PURPOSE: This study evaluated the short-term outcomes and prognosis after laparoscopic total gastrectomy (LTG) in elderly patients aged ≥ 80 years in a multicenter retrospective cohort study using propensity score matching. METHODS: We retrospectively enrolled 440 patients who underwent curative LTG for gastric cancer at six institutions between January 2004 and December 2018. Patients were categorized into an elderly patient group (EG; age ≥ 80 years) and non-elderly patient group (non-EG; age < 80 years). Patients were matched using the following propensity score covariates: sex, body mass index, American Society of Anesthesiologists physical status, extent of lymph node dissection, and Japanese Classification of Gastric Carcinoma stage. Short-term outcomes and prognoses were compared. RESULTS: We identified 37 propensity score-matched pairs. The median operative time was significantly shorter, and postoperative stay was longer in the EG. In terms of postoperative outcomes, the rates of all complications were comparable. The median follow-up period of the EG and non-EG was 11.5 (1-106.4) months and 35.7 (1-110.0) months, respectively; there were significant differences in 5-year overall survival between the two groups (EG, 58.5% vs. non-EG, 91.5%; P = 0.031). However, there were no significant differences in 5-year disease-specific survival (EG, 62.1% vs. non-EG, 91.5%; P = 0.068) or 5-year disease-free survival (EG, 52.9% vs. non-EG, 60.8%; P = 0.132). CONCLUSIONS: LTG seems to be safe and feasible in elderly patients. LTG had a limited effect on morbidity, disease recurrence, and survival in elderly patients. Therefore, age should not prevent elderly patients from benefitting from LTG.

Development of a systematic telesimulation curriculum for laparoscopic inguinal hernia repair.

Purpose: Telesimulation, whereby learners telecommunicate and use simulator resources to receive education at an off-site location, has been used to educate surgical trainees about how to perform basic surgical procedures. However, it has not yet been used for advanced surgical procedures. We aimed to develop a telesimulation curriculum to teach a common laparoscopic procedure called transabdominal preperitoneal (TAPP) repair and to explore the feasibility of its use. Methods: Learning objectives were created to develop a telesimulation curriculum that included didactic telelecture and telesimulation training. Pre-tests and post-tests to assess the didactic materials were developed and assessed among surgeons with various experiences. We assessed the feasibility of the telelecture and telesimulation separately. Pre-tests, post-tests, and questionnaires were used to assess the telelectures. We created a TAPP repair telesimulation system and checked for problems during training. Trainees were assessed to determine their skill improvement using previously published assessment tools and questionnaires. Results: A didactic telelecture was developed based on the learning objectives using an expert consensus and pilot-tested among five participants. After the lecture, their test scores improved and they expressed positive opinions about the usefulness of telelectures. The TAPP repair telesimulation training was pilot-tested among three trainees. No technical problems occurred during training. All trainees improved their skills after the telesimulation training and agreed that the training was useful for learning the TAPP repair procedure. Conclusions: We systematically developed a telesimulation curriculum for the TAPP repair procedure and demonstrated its feasibility among learners.

A Multicenter Retrospective Study Comparing Surgical Outcomes Between the Overlap Method and Functional Method for Esophagojejunostomy in Laparoscopic Total Gastrectomy: Analysis Using Propensity Score Matching.

BACKGROUND: This study aimed to compare the postoperative outcomes after laparoscopic total gastrectomy (LTG) with esophagojejunostomy (EJS) performed using the overlap method or the functional method in a multicenter retrospective study with propensity score matching. METHODS: We retrospectively enrolled all patients who underwent curative LTG for gastric cancer at 6 institutions between January 2004 and December 2018. Patients were categorized into the overlap group (OG) or functional group (FG) based on the type of anastomosis used in EJS. Patients in the groups were matched using the following propensity score covariates: age, sex, body mass index, American Society of Anesthesiologists physical status, extent of lymph node dissection, and Japanese Classification of Gastric Carcinoma stage. The surgical results and postoperative outcomes were compared. RESULTS: We identified 69 propensity score-matched pairs among 440 patients who underwent LTG. There was no significant between-group difference in the median operative time, intraoperative blood, or number of lymph nodes resected. In terms of postoperative outcomes, the rates of all complications [Clavien-Dindo (CD) classification ≥II; OG 13.0 vs. FG 24.6%, respectively; P=0.082], complications more severe than CD grade III (OG 8.7 vs. FG 18.8%, respectively; P=0.084), and the occurrence of EJS leakage and stenosis more severe than CD grade III (OG 7.3% vs. FG 2.9%, P=0.245; OG 1.5 vs. FG 8.7%, P=0.115, respectively) were comparable. The median follow-up period was 830 days (range, 18 to 3376 d), and there were no differences in overall survival between the 2 groups. CONCLUSIONS: There was no difference in surgical outcomes and overall survival based on the type of anastomosis used for EJS after LTG. Therefore, selection of anastomosis in EJS should be based on each surgeon's preference and experience.

Efficiency of the novel quenching-probe PCR method to detect 23S rRNA mutations in children with Mycoplasma pneumoniae infection.

An automated rapid molecular diagnostic kit (Smart Gene Myco) was recently developed for individual detection of Mycoplasma pneumoniae (MP) genes. This new testing approach requires no special equipment and skills and can be completed within 50 min. We prospectively evaluated this diagnostic kit, along with other conventional tests, for pneumonia diagnosis in children. Samples from 98 children (50 boys and 48 girls; aged 1-14 years; mean: 4.7 ± 2.1 years; median: 4 years) clinically diagnosed with pneumonia were tested for MP using real-time polymerase chain reaction (RT-PCR) as a reference method. Results from three molecular diagnostic tests, serum anti-MP antibodies, and MP culture were compared to RT-PCR data. Among the 98 children, 38 were positive for MP. All molecular diagnostic results showed complete concordance with the RT-PCR data. The sensitivity of the culture was 64%, whereas the sensitivities of the ImmunoCard Mycoplasma and SERODIA Myco II kits were lower (39% and 29%, respectively). Furthermore, a significant positive correlation was found between MP copy numbers and the culture test sensitivity (r = 0.95, p = 0.048). Macrolide-resistance mutations in the 23S ribosomal RNA gene were detected in 24 of 38 children using Smart Gene Myco based on quenching-probe PCR, which was confirmed by direct sequencing, revealing all mutations as A2063G. This is the first study to evaluate the clinical utility of the Smart Gene Myco kit, demonstrating that it is a fast and reliable method to support timely therapeutic decisions in children with MP pneumonia.

A case of thymic basaloid carcinoma with rectal carcinoma.

INTRODUCTION: Thymic basaloid carcinoma is rare, as only about 40 reports have described it since the initial report. Thymoma and thymic carcinomas increase the risk of other malignancies, but concurrent thymic basaloid carcinoma and another malignancy has not been reported. We presented a rare case of thymic basaloid carcinoma with rectal carcinoma. CASE PRESENTATION: Computed tomography revealed an anterior mediastinal mass and rectal wall thickening, and colonoscopy identified a rectal type 2 tumor in a 68-year-old man. Total thymectomy via a median sternotomy was performed, and the thymic tumor was histopathologically confirmed as stage II thymic basaloid carcinoma. Subsequent laparoscopic low anterior resection indicated stage IIIa rectal carcinoma. Adjuvant chemotherapy was administered for the rectal cancer. DISCUSSION: Concurrent thymic and extrathymic tumors is rare condition. There are few reports of thymic basaloid carcinoma, and it is unclear whether this tumor, like common thymoma, increase the risk of extrathymic malignancies. Further studies in more patients are needed to elucidate the nature of this tumor. CONCLUSION: To our knowledge, this is the first case report of thymic basaloid carcinoma concurrent another carcinoma. Aggressive treatment including surgery should be considered aiming at radical cure.

The effect of the body mass index on the short-term surgical outcomes of laparoscopic total gastrectomy: A propensity score-matched study.

PURPOSE: This study aimed to evaluate the relationship between the body mass index (BMI) and the short-term outcomes of laparoscopic total gastrectomy (LTG). SUBJECTS AND METHODS: Data of patients who underwent LTG for gastric cancer at six institutions between 2004 and 2018 were retrospectively collected. The patients were classified into three groups: low BMI (<18.5 kg/m2), normal BMI (≥18.5 and <25 kg/m2) and high BMI (≥25 kg/m2). In these patients, clinicopathological variables were analysed using propensity score matching for age, sex, the American Society of Anaesthesiologists physical state, clinical stage, surgical method, D2 lymph node dissection, combined resection of other organs, anastomosis method and jejunal pouch reconstruction. The surgical results and post-operative outcomes were compared among the three groups. RESULTS: A total of 82 patients were matched in the analysis of the low BMI and normal BMI groups. There were no differences in operative time (P = 0.693), blood loss (P = 0.150), post-operative complication (P = 0.762) and post-operative hospital stay (P = 0.448). In the analysis of the normal BMI and high BMI groups, 208 patients were matched. There were also no differences in blood loss (P = 0.377), post-operative complication (P = 0.249) and post-operative hospital stay (P = 0.676). However, the operative time was significantly longer in the high BMI group (P = 0.023). CONCLUSIONS: Despite the association with a longer operative time in the high BMI group, BMI had no significant effect on the surgical outcomes of LTG. LTG could be performed safely regardless of BMI.

Identifying the Essential Portions of the Skill Acquisition Process Using Item Response Theory.

OBJECTIVE: Item response theory (IRT) was originally developed to make performance assessments more accurate. However, IRT analysis of the intraoperative performance of surgical trainees could help identify the elements that the trainees find difficult during the skill acquisition process. The aim of this study was to identify the essential portions of the skill acquisition process of a surgical procedure using the IRT. DESIGN: The 24-item assessment checklist was used to evaluate a recorded intra-operative performance of a laparoscopic inguinal hernia repair. The scores were analyzed using IRT to calculate the difficulty and discrimination level of each item. SETTING: Fifteen institutes. PARTICIPANTS: Thirty surgical trainees. RESULTS: A total of 123 assessments were analyzed. The item analysis showed the procedure specific item "traction of peritoneum (difficulty: -0.45; discrimination: 19.37)" and generic items "instrument handling (difficulty: -0.59; discrimination: 3.82)" and "flow of procedure (difficulty: 0.09; discrimination: 3.27)" to be key elements in the skill acquisition process of the procedure. CONCLUSIONS: Key elements in the skill acquisition process of the procedure were quantitatively identified by applying the IRT analysis. This could lead to the use of IRT in designing and developing a more effective training curriculum.

Development of a novel training system for laparoscopic inguinal hernia repair.

Background: Laparoscopic inguinal hernia repair is considered technically difficult. Although a simulation-based curriculum has been developed to help trainees, access to simulation training outside North America is limited. This study aimed to develop an educational system for the transabdominal preperitoneal (TAPP) approach based on the TAPP checklist, an assessment tool we had developed and validated earlier. Material and methods: Consensus within the TAPP education working group consisting of local TAPP experts, hernia experts and a surgical educator to develop educational tools and the educational system based on the TAPP checklist. The system was piloted in several institutes, and participants were surveyed on its efficacy. Results: We systematically developed an educational video and training manual explaining each item of the TAPP checklist and conveying basic knowledge of the procedure. We integrated the training tool with evaluation and feedback to develop an educational system. In a pilot study, seven trainees at five hospitals were trained using this system and found it very useful for mastering the TAPP procedure. Conclusions: We have developed a training system for TAPP procedure and successfully implemented it in several hospitals. Further research will focus on the educational value of this tool.

Predicting response to sepantronium bromide (YM155), a survivin suppressant, by PET imaging with [11C]YM155.

INTRODUCTION: Sepantronium bromide (YM155) is a survivin suppressant that induces apoptosis in tumor cells. Although YM155 induces tumor regression in various tumor types in vivo, phase I and II studies demonstrated responding and non-responding patient populations. We investigated 11C-labeled YM155 ([11C]YM155) used as a positron emission tomography (PET) tracer to assess whether tumor uptake of [11C]YM155 correlated with its anti-tumor effect, thereby allowing identification of patients who would respond to YM155 treatment. METHODS: (1) Uptake of YM155 was measured in 39 human cancer cell lines in vitro using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). (2) In vivo tumor uptake was assessed in xenografted mice and total body distribution was evaluated in a cynomolgus monkey using [11C]YM155 with PET/computed tomography (CT) (mice) and PET (monkey) imaging. RESULTS: Intracellular uptake of YM155 in human cancer cell lines correlated well with its in vitro efficacy measured by GI50 (Pearson's r = -0.5709). Similarly, in vivo studies using tumor xenografted mice showed that tumors sensitive to YM155 demonstrated robust uptake of [11C]YM155, whereas insensitive tumors demonstrated low uptake. In the monkey, the biodistribution of [11C]YM155 indicated low accumulation in lung, breast, head, and neck and was only significant in organs involved with drug clearance: i.e. liver, kidneys, and bladder. CONCLUSIONS: Robust uptake of [11C]YM155 by a tumor appears to be a positive predictive marker for a good response to YM155. The findings suggest the potential utility of PET/CT imaging with [11C]YM155 for selection of patients whose tumors are likely to respond to YM155. ADVANCES IN KNOWLEDGE: YM155 efficacy correlated closely with its in vitro intracellular uptake and uptake on [11C]YM155 PET imaging. [11C]YM155 PET may predict tumor sensitivity to YM155. IMPLICATIONS FOR PATIENT CARE: The concept that tumor response can be accurately predicted prior to chemotherapy should be exploited to improve cancer treatment outcomes through judicious patient selection. The small molecule sepantronium bromide (YM155), a survivin suppressant, has been developed for the treatment of several cancers, including non-Hodgkin lymphoma, lung cancer, and breast cancer. The preferentially high in vitro uptake of YM155 by YM155-sensitive cancer cells and the high in vivo uptake of [11C]YM155 in YM155-sensitive tumors demonstrated by PET imaging suggest the potential utility of performing [11C]YM155 PET to allow the identification of patients with YM155-sensitive tumors.

Solitary thymic metastasis of breast cancer 13 years after surgery.

A 59-year-old woman was noted to have an anterior mediastinal mass on computed tomography at a regular follow-up 13 years after initial surgery for left breast cancer. Magnetic resonance imaging showed an anterior mediastinal mass. A total thymectomy with excision of surrounding lymphoid tissue was performed. Pathological examination of the resected tumor confirmed the diagnosis of thymic metastasis from breast cancer. The patient has been alive for 6 years after thymectomy. Metastases to the thymus are rare, but long-term survival can be expected with appropriate treatment.

Design and Synthesis of an Easily Obtainable Maleimide Reagent N-[2-(4-[18F]fluoro-N-methylbenzenesulfonamido)ethyl]maleimide ([18F]FBSEM) to Radiolabel Thiols in Proteins.

An easily obtainable thiol-selective labeling reagent [18F]FBSEM (N-[2-(4-[18F]fluoro-N-methylbenzenesulfonamido)ethyl]maleimide) was developed. The advantage of the design is that the precursor and [18F]FBSEM have the same backbone and backbone construction is not required; in contrast, known thiol-specific labeling reagents do require backbone construction, and this is thought to be the cause of their complicated synthesis. [18F]FBSEM was successfully obtained in higher yield (25%) and in a simpler way (two fluorination and deprotection steps in 65 min) than the widely used [18F]FBEM (N-[2-(4-[18F]fluorobenzamide)ethyl]maleimide). The labeling efficacy of [18F]FBSEM was confirmed by conjugation with glutathione. [18F]FBSEM is a promising labeling agent for proteins.

Preclinical Evaluation of an Anti-Nectin-4 ImmunoPET Reagent in Tumor-Bearing Mice and Biodistribution Studies in Cynomolgus Monkeys.

PURPOSE: Nectin-4 is selectively overexpressed in a variety of cancers and is currently under clinical investigation as a therapeutic target. A monoclonal antibody against nectin-4 (AGS-22M6) was evaluated as an Immuno-positron emission tomography (ImmunoPET) reagent. Its ability to assay nectin-4 expression as well as detect nectin-4 positive tumors in the liver and bone was evaluated using mouse models. PROCEDURES: The biodistribution of [(89)Zr]AGS-22M6 was evaluated in mice bearing tumors with varying levels of nectin-4 expression. An isogenic breast cancer tumor line was used to model metastatic liver and bone disease in mice. The biodistribution of [(18)F]AGS-22M6 in cynomolgus monkeys was evaluated. RESULTS: A positive correlation was demonstrated between tumor nectin-4 expression and [(89)Zr]AGS-22M6 uptake. Tumors in the liver and bone were detected and differentiated based on nectin-4 expression. [(18)F]AGS-22M6 showed limited uptake in cynomolgus monkey tissues. CONCLUSIONS: [(89)Zr]AGS-22M6 is a promising ImmunoPET reagent that can assay nectin-4 expression in both primary and metastatic lesions.

Development and validation of a checklist for assessing recorded performance of laparoscopic inguinal hernia repair.

BACKGROUND: Despite a need for video assessment for the performance transabdominal preperitoneal procedure (TAPP), the present assessment tools have not been validated for the use of evaluation of the recorded performance. We aimed to develop a checklist for the evaluation of the recorded performance of TAPP. METHODS: The TAPP checklist was developed by hernia experts from multiple institutes. Thirty unedited TAPP videos were rated by 3-blinded hernia experts. Inter-rater reliability and construct and concurrent validities were evaluated. RESULTS: The inter-rater reliability for 3 raters was .75 (95% confidence interval .60 to .86). The median total score of each group demonstrated a significant difference among experienced (>50 TAPP), intermediate (≥10 TAPP, <50), and novice (<10 TAPP) surgeons (P < .001). The checklist score showed a high correlation with TAPP experience and previously validated global scale for laparoscopic inguinal hernia repair. CONCLUSIONS: The TAPP checklist is a valid metrics for the assessment of the recorded TAPP performance.

Functional imaging of pharmacological action of SGLT2 inhibitor ipragliflozin via PET imaging using 11C-MDG.

Sodium-dependent glucose cotransporter 2 (SGLT2) is a pharmacological target of type 2 diabetes mellitus. The aim of this study was to noninvasively visualize the pharmacological action of a selective SGLT2 inhibitor ipragliflozin in the kidney using positron emission tomography (PET) imaging with 11C-methyl-d-glucoside (11C-MDG), an SGLT-specific radio-labeled substrate. PET imaging with 11C-MDG in vehicle-treated rats demonstrated that intravenously injected 11C-MDG substantially accumulated in the renal cortex, reflecting that the compound was reabsorbed by SGLTs. In contrast, ipragliflozin-treated rats showed significantly lower uptake of 11C-MDG in renal cortex in a dose-related manner, suggesting that ipragliflozin inhibited the renal reabsorption of 11C-MDG. This method of visualizing the mode of action of an SGLT2 inhibitor in vivo has demonstrated the drug's mechanism in reducing renal glucose reabsorption in kidney in living animals.

PET imaging for tyrosine kinase inhibitor (TKI) biodistribution in mice.

Receptor tyrosine kinases play a critical role in cell growth, survival, and proliferation, and are considered potential molecular targets for the treatment of cancer. Although several tyrosine kinase inhibitors (TKIs), such as erlotinib and gefitinib, have demonstrated clinical efficacy via the inhibition of the epidermal growth factor receptor (EGFR), most TKIs are only effective in a small proportion of patients. Positron emission tomography (PET) imaging is a methodology of molecular imaging based on nuclear imaging. PET imaging in combination with radiolabeled TKIs improves accuracy of quantitative imaging strategies and the probability of successful drug development, and may facilitate the stratification of patients. Here, we describe a protocol for PET imaging using radiolabeled TKI in preclinical trials.