Predictive value of SUVmax from initial 18F-FDG PET/CT scans for treatment outcomes in endometrial cancer patients undergoing fertility sparing management.

OBJECTIVE: To evaluate whether the maximum standardized uptake value (SUVmax) from initial 18F-FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) scans could be a predictor of complete response and recurrence in patients with endometrial cancer who are undergoing fertility sparing management. METHODS: We conducted a retrospective review of patients who were diagnosed with endometrial cancer through biopsy and chose to undergo fertility sparing management using progestin at the Asan Medical Center, from January 2011 to December 2020. Of these, 113 patients who had an 18-FDG-PET/CT scan before starting treatment were included in our study. We measured SUVmax and examined its correlation with complete response and time to progression after achieving complete response to progestin therapy. RESULTS: Of 113 patients, 73 (64.6%) achieved a complete response through fertility sparing management. The receiver operating characteristic curve analysis revealed that the optimal cut-off value of SUVmax for predicting complete response was 6.2 (sensitivity 79.5%, specificity 57.5%, p=0.006). After analyzing recurrence in the 73 patients who achieved complete response, we found that patients with an SUVmax value >6.2 had a significantly shorter time to progression compared with those with a value <6.2. (p=0.04). CONCLUSIONS: SUVmax values of PET-CT, along with other clinicopathological parameters, could be used to predict treatment response and recurrence risk in patients with stage I endometrial cancer undergoing fertility sparing management.

53 GBd PAM-4 fully-integrated silicon photonics transmitter with a hybrid flip-chip bonded laser.

We present a fully-integrated single-lane 53 GBd PAM-4 silicon photonics (SiPh) transmitter (Tx) with a flip-chip bonded laser diode (LD). The LD is butt-coupled to a Si edge coupler including a SiO2 suspended spot-size converter. The coupled power exceeds 10 dBm with a 1 dB allowable misalignment of 2.3 µm. The RF and eye performances of the Tx are evaluated. Extinction ratio >5 dB is obtained at 3.5 Vppd voltage swing. Aided by silicon capacitors, the Tx decouples parasitic inductances leading to remarkable improvements in the eye openings and transmitter dispersion eye closure quaternary by 1.16 dB. By implementing the fully-integrated Tx with driver packaging, we successfully demonstrate 106 Gb/s real-time operation satisfying KP4-FEC threshold at -5 dBm receiver sensitivity.

Diagnostic performance of deep learning models for detecting bone metastasis on whole-body bone scan in prostate cancer.

PURPOSE: We evaluated the performance of deep learning classifiers for bone scans of prostate cancer patients. METHODS: A total of 9113 consecutive bone scans (5342 prostate cancer patients) were initially evaluated. Bone scans were labeled as positive/negative for bone metastasis using clinical reports and image review for ground truth diagnosis. Two different 2D convolutional neural network (CNN) architectures were proposed: (1) whole body-based (WB) and (2) tandem architectures integrating whole body and local patches, here named as "global-local unified emphasis" (GLUE). Both models were trained using abundant (72%:8%:20% for training:validation:test sets) and limited training data (10%:40%:50%). The allocation of test sets was rotated across all images: therefore, fivefold and twofold cross-validation test results were available for abundant and limited settings, respectively. RESULTS: A total of 2991 positive and 6142 negative bone scans were used as input. For the abundant training setting, the receiver operating characteristics curves of both the GLUE and WB models indicated excellent diagnostic ability in terms of the area under the curve (GLUE: 0.936-0.955, WB: 0.933-0.957, P > 0.05 in four of the fivefold tests). The overall accuracies of the GLUE and WB models were 0.900 and 0.889, respectively. With the limited training setting, the GLUE models showed significantly higher AUCs than the WB models (0.894-0.908 vs. 0.870-0.877, P < 0.0001). CONCLUSION: Our 2D-CNN models accurately classified bone scans of prostate cancer patients. While both showed excellent performance with the abundant dataset, the GLUE model showed higher performance than the WB model in the limited data setting.

Hyaluronic acid filler injection for deep nasolabial folds: A novel intraoral approach.

Hyaluronic acid filler injection is a minimally invasive procedure for facial rejuvenation that involves injecting filling materials to correct the volume or augment specific areas in the face. Deep nasolabial folds are a common concern in aging people. The simplest way to correct a deep nasolabial fold to rejuvenate the face is to inject Ristow's space with hyaluronic acid fillers. However, conventional injection methods, such as percutaneous injections using a needle, can cause severe complications, such as skin necrosis or blindness due to intravascular injections. Therefore, the aim of the present study was to introduce a safe technique for intraoral filler injections in deep nasolabial folds and review related anatomic features to evaluate the safety of this technique.

A novel needle-free microjet drug injector using Er:YAG LASER: A completely new concept of transdermal drug delivery system.

The skin barrier effectively inhibits the penetration of substances; therefore, drug delivery, especially the delivery of drugs that are hydrophilic, through the skin, is challenging. Objectives: Physicians in the esthetic field now use the transdermal drug delivery system to attempt to deliver esthetic materials, such as hyaluronic acid and poly-DL-lactic acid into the skin. Conventionally, esthetic physicians manually injected these materials using needle syringes into the dermis layer. However, the injection is often irregular, imprecise, slow, and painful. Injector devices have been developed to overcome these limitations. A total of five Korean cadavers (that of three men and two women with a mean age of 69.2 years; range, 60-73 years) underwent laser injection. We used a device called Er:YAG LASER to create the pressure needed for microjet delivery to the skin of the cadaver. Discussion: In this study, the first LASER pressure-based, needle-free microjet injector was used to deliver drugs effectively into the dermis of a cadaver. This study showed that a novel needle-free microjet injector using Er:YAG LASER can introduce beneficial, liquid, esthetic drugs into the papillary dermal layer (depth of 300um) with minimal epidermal damage.

Anatomical consideration of deep calf veins: application to catheter-directed thrombolysis.

PURPOSE: An antegrade approach is frequently used in catheter-directed thrombolysis to remove deep-vein thrombosis. However, the antegrade approach is difficult when accessing veins with small diameters; therefore, understanding the variation of deep calf vein is important. METHODS: This study measured the diameters and surface areas of the proximal and distal posterior tibial vein, peroneal vein, and anterior tibial vein to determine which are preferable for venous access. This study dissected 132 legs from Korean and Thai cadavers. The proximal and distal posterior tibial vein, peroneal vein, and anterior tibial vein were scanned and measured. RESULTS: The mean diameter and surface area were largest for the proximal tibial vein, at 6.34 mm and 0.312 cm2, respectively, followed by the anterior tibial vein (5.22 mm and 0.213 cm2), distal posterior tibial vein (3.29 mm and 0.091 cm2), and peroneal vein (3.43 mm and 0.081 cm2). The proximal posterior tibial vein and anterior tibial vein have large diameters and surface areas, which make them ideal for applying an antegrade approach in catheter-directed thrombolysis. CONCLUSIONS: The distal posterior tibial vein and peroneal vein are not recommended due to their smaller surface areas and also the anatomical variations therein.

Deep learning detection of prostate cancer recurrence with 18F-FACBC (fluciclovine, Axumin®) positron emission tomography.

PURPOSE: To evaluate the performance of deep learning (DL) classifiers in discriminating normal and abnormal 18F-FACBC (fluciclovine, Axumin®) PET scans based on the presence of tumor recurrence and/or metastases in patients with prostate cancer (PC) and biochemical recurrence (BCR). METHODS: A total of 251 consecutive 18F-fluciclovine PET scans were acquired between September 2017 and June 2019 in 233 PC patients with BCR (18 patients had 2 scans). PET images were labeled as normal or abnormal using clinical reports as the ground truth. Convolutional neural network (CNN) models were trained using two different architectures, a 2D-CNN (ResNet-50) using single slices (slice-based approach) and the same 2D-CNN and a 3D-CNN (ResNet-14) using a hundred slices per PET image (case-based approach). Models' performances were evaluated on independent test datasets. RESULTS: For the 2D-CNN slice-based approach, 6800 and 536 slices were used for training and test datasets, respectively. The sensitivity and specificity of this model were 90.7% and 95.1%, and the area under the curve (AUC) of receiver operating characteristic curve was 0.971 (p < 0.001). For the case-based approaches using both 2D-CNN and 3D-CNN architectures, a training dataset of 100 images and a test dataset of 28 images were randomly allocated. The sensitivity, specificity, and AUC to discriminate abnormal images by the 2D-CNN and 3D-CNN case-based approaches were 85.7%, 71.4%, and 0.750 (p = 0.013) and 71.4%, 71.4%, and 0.699 (p = 0.053), respectively. CONCLUSION: DL accurately classifies abnormal 18F-fluciclovine PET images of the pelvis in patients with BCR of PC. A DL classifier using single slice prediction had superior performance over case-based prediction.

Clinicopathologic risk factors of radioactive iodine therapy based on response assessment in patients with differentiated thyroid cancer: a multicenter retrospective cohort study.

PURPOSE: We investigated whether predictive clinicopathologic factors can be affected by different response criteria and how the clinical usefulness of radioactive iodine (RAI) therapy should be evaluated considering variable factors in patients with differentiated thyroid carcinoma (DTC). METHODS: A total of 1563 patients with DTC who underwent first RAI therapy after total or near total thyroidectomy were retrospectively enrolled from 25 hospitals. Response to therapy was evaluated with two different protocols based on combination of biochemical and imaging studies: (1) serum thyroglobulin (Tg) and neck ultrasonography (US) and (2) serum Tg, neck US, and radioiodine scan. The responses to therapy were classified into excellent and non-excellent or acceptable and non-acceptable to minimize the effect of non-specific imaging findings. We investigated which factors were associated with response to therapy depending on the follow-up protocols as well as response classifications. Multivariate logistic regression analysis was performed to identify factors significantly predicting response to therapy. RESULTS: The proportion of patients in the excellent response group significantly decreased from 76.5 to 59.6% when radioiodine scan was added to the follow-up protocol (P < 0.001). Preparation method (recombinant human TSH vs. thyroid hormone withdrawal) was a significant factor for excellent response prediction evaluated with radioiodine scan (OR 2.129; 95% CI 1.687-2.685; P < 0.001) but was not for other types of response classifications. Administered RAI activity, which was classified as low (1.11 GBq) or high (3.7 GBq or higher), significantly predicted both excellent and acceptable responses regardless of the follow-up protocol. CONCLUSIONS: The clinical impact of factors related to response prediction differed depending on the follow-up protocol or classification of response criteria. A high administered activity of RAI was a significant factor predicting a favorable response to therapy regardless of the follow-up protocol or classification of response criteria.

Feasibility and effectiveness of treatment strategy of tandem high-dose chemotherapy and autologous stem cell transplantation in combination with 131 I-MIBG therapy for high-risk neuroblastoma.

This study was performed to evaluate the safety and effectiveness of tandem HDCT/ASCT combined with targeted radiotherapy using 131 I-MIBG for high-risk neuroblastoma. Patients with high-risk neuroblastoma were treated with 8 to 10 cycles of induction chemotherapy before tandem HDCT/ASCT. Patients received 131 I-MIBG treatment before the second HDCT/ASCT. Local radiotherapy and maintenance therapy were performed after tandem HDCT/ASCT. Between 2012 and 2016, 19 patients were diagnosed with high-risk neuroblastoma in our institution and 18 of them received tandem HDCT/ASCT combined with 131 I-MIBG therapy. For the first HDCT/ASCT regimen, 12 patients received busulfan/melphalan and six patients received melphalan/etoposide/carboplatin. The second HDCT included ThioCy. The median dose of 131 I-MIBG was 17.2 mCi/kg for the first eight patients, while 12 patients in the latter period of the study received reduced dose of 10.7 mCi/kg. The 5-year OS and EFS rates were 79% and 61%, respectively, for all 19 patients with high-risk neuroblastoma, and 83% and 64%, respectively, for 18 patients who completed tandem HDCT/ASCT combined with 131 I-MIBG therapy. Six patients experienced disease relapse and five patients died. Treatment-related mortality was not observed. Among 15 evaluable patients, 11 patients (73%) developed hypothyroidism, six patients (40%) had CKD, and six patients (40%) had growth failure. Hypothyroidism and growth failure were less frequent in patients who received reduced doses of 131 I-MIBG therapy. Tandem HDCT/ASCT combined with HD 131 I-MIBG therapy could be feasible for patients with high-risk neuroblastoma with acceptable toxicity profiles and favorable outcomes.

Preoperative [18F]FDG PET/CT tumour heterogeneity index in patients with uterine leiomyosarcoma: a multicentre retrospective study.

PURPOSE: We investigated the prognostic value of the tumour heterogeneity index determined on preoperative [18F]FDG PET/CT in patients with uterine leiomyosarcoma (LMS). METHODS: We retrospectively reviewed patients with uterine LMS who underwent preoperative [18F]FDG PET/CT scans at three tertiary referral hospitals. The PET/CT parameters maximum standardized uptake value of the primary tumour (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis were assessed. The negative values of the MTV linear regression slope (nMLRS) according to the SUV thresholds of 2.5 and 3.0 were determined as the tumour heterogeneity index. The value of PET/CT-derived parameters in predicting progression-free survival (PFS) and overall survival (OS) were determined in regression analyses. RESULTS: Clinicopathological and PET/CT data from 16 patients were reviewed. The median postsurgical follow-up was 21 months (range 4-82 months), and 12 patients (75.0%) experienced recurrence. Tumour size (P = 0.017), SUVmax (P = 0.019), MTV (P = 0.016) and nMLRS (P = 0.008) were significant prognostic factors for recurrence. MTV (P = 0.048) and nMLRS (P = 0.045) were significant prognostic factors for patient survival. nMLRS was correlated with clinicopathological parameters including tumour size (Pearson's correlation coefficient γ = 0.825, P < 0.001) and lymph node metastasis (γ = 0.721, P = 0.004). Patient groups categorized according to the nMLRS cut-off value showed significant differences in PFS (P = 0.033) and OS (P = 0.044). CONCLUSION: The preoperative tumour heterogeneity index obtained using the MTV linear regression slope may be a novel and useful prognostic marker in uterine LMS.

The Value of Preoperative Positron Emission Tomography/Computed Tomography in Node-Negative Endometrial Cancer on Magnetic Resonance Imaging.

OBJECTIVE: The aim of this study was to investigate the value of [18F]fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in predicting lymph node status in node-negative endometrial cancer on preoperative magnetic resonance imaging (MRI). METHODS: Patients with endometrial cancer who underwent both preoperative MRI and FDG-PET/CT followed by hysterectomy and lymphadenectomy were initially included. We then enrolled patients with MRI-defined node-negative disease (lymph nodes <1 cm in the short-axis diameter, or no visible lymph node). Histologic examination was the gold standard for lymph node metastasis diagnosis. The diagnostic performance of FDG-PET/CT in predicting lymph node metastasis was calculated in patient-by-patient and lymph node station-by-station analyses. RESULTS: On preoperative MRI, 362 patients had no lymph node metastasis. All patients underwent pelvic lymph node dissection and 118 patients underwent further para-aortic lymph node dissection. From 2099 lymph node stations, 10,238 lymph nodes were retrieved. Twenty-seven patients (7.5%) had lymph node metastasis in 49 lymph node stations (2.3%) on pathologic examination. FDG-PET/CT identified lymph node metastasis in five patients (18.5%) and eight lymph node stations (16.3%). The median diameter of false-negative metastatic lymph nodes was 6 mm (range 1-22) in the long axis and 3 mm (range 1-11) in the short axis. For para-aortic lymph nodes, FDG-PET/CT diagnosed 2 of 11 patients (18.1%) with para-aortic lymph node metastasis, and 3 of 12 para-aortic lymph node stations (25%) with metastasis. CONCLUSION: Preoperative FDG-PET/CT has low value in predicting lymph node metastasis in node-negative endometrial cancer on preoperative MRI.

Endoscopic biliary stent insertion through specialized duodenal stent for combined malignant biliary and duodenal obstruction facilitated by stent or PTBD guidance.

OBJECTIVES: Endoscopic stenting for combined malignant biliary and duodenal obstruction is technically demanding. However, this procedure can be facilitated when there is guidance from previously inserted stent or PTBD tube. This study aimed to evaluate the feasibility and clinical success rate of endoscopic placement of biliary self-expandable metal stent (SEMS) through duodenal SEMS in patients with combined biliary and duodenal obstruction due to inoperable or metastatic periampullary malignancy. MATERIALS AND METHODS: A total of 12 patients with combined malignant biliary and duodenal stricture underwent insertion of biliary SEMS through the mesh of specialized duodenal SEMS from July 2012 to October 2016. Technical and clinical success rate, adverse events and survival after completion of SEMS insertion were evaluated. RESULTS: The duodenal strictures were located in the first portion of the duodenum in four patients (Type I), in the second portion in three patients (Type II), and in the third portion in five patients (Type III). Technical success rate of combined metallic stenting was 91.7%. Insertion of biliary SEMS was guided by previously inserted biliary SEMS in nine patients, plastic stent in one patient, and PTBD in two patients. Clinical success rate was 90.9%. There were no early adverse events after the procedure. Mean survival period after combined metallic stenting was 91.9 days (range: 15-245 days). CONCLUSIONS: Endoscopic placement of biliary SEMS through duodenal SEMS is feasible with high success rates and relatively easy when there is guidance. This method can be a good alternative for palliation in patients with combined biliary and duodenal obstruction.

Comparison of MRI and 18F-FDG PET/CT in the preoperative evaluation of uterine carcinosarcoma.

OBJECTIVE: To compare the validities of magnetic resonance imaging (MRI) and (18)F-fluoro-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in preoperative evaluation of uterine carcinosarcoma. METHODS: Pathologic results of primary tumor lesions and paraaortic and pelvic lymph node (LN) areas were compared with the preoperative image findings. Differences in the validity parameters of both images were compared using McNemar test. RESULTS: For detecting primary tumor lesions (n=56), the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for (18)F-FDG PET/CT versus MRI were 98.1% versus 98.1% (P=1.000), 33.3% versus 100% (P=0.157), 94.6% versus 98.2% (P=0.500), 96.3% versus 100%, and 50% versus 75%, respectively. For paraaortic LN areas, the values were 77.8% versus 51.9% (P=0.016), 90.2% versus 100% (P=0.025), 85.9% versus 83.3% (P=0.774), 80.8% versus 100%, and 88.5% versus 79.7%, respectively. For pelvic LN areas, the values were 61.1% versus 50% (P=0.125), 86.8% versus 89.5% (P=0.727), 78.6% versus 76.8% (P=0.774), 68.8% versus 69.2%, and 82.5% versus 79.1%, respectively. For extrauterine disease, the patient-based values for (18)F-FDG PET/CT were 100%, 78.9%, 85.7%, 69.2%, and 100%, respectively. CONCLUSION: In patients with uterine carcinosarcoma, (18)F-FDG PET/CT is comparable to MRI in detecting primary uterine lesions. For predicting LN metastases, though (18)F-FDG PET/CT might be insufficient for replacing lymphadenectomy or MRI, it might allow lymphadenectomy to be omitted in poor surgical candidates. For detecting extrauterine metastases, it could also be useful to identify unsuspected disease.

Biological evaluation of new [(18) F]F-labeled synthetic amino acid derivatives as oncologic radiotracers.

The present study evaluated the tumoral uptake of the novel synthetic amino acid positron emission tomography (PET) tracers (S)-2-amino-3-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)propanoic acid (AMC-101), (S)-2-amino-4-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)butanoic acid (AMC-102), and (S)-2-amino-5-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)pentanoic acid (AMC-103), all of which are (S)-2-amino-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)alkyl acids. In vitro cellular uptake was investigated using the rat glioma cell lines 9L and C6. In vitro competitive inhibition tests were performed to identify the involvement of specific amino acid transporters. In vivo dynamic PET images of 9L xenograft tumor-bearing model mice were acquired over 2 h after AMC administration. [(18) F]FDOPA PET studies were performed with and without S-carbidopa pretreatment for comparison. All three AMCs exhibited good in vitro cell uptake through the L and alanine-serine-cysteine transporters and enabled clear tumor visualization on PET, leaving the brain devoid of the tracer. Thirty minutes after injection, the mean tumor standardized uptake values were 1.59 ± 0.05, 1.89 ± 0.27, and 1.74 ± 0.13 for AMC-101, AMC-102, and AMC-103, respectively. Although the tumor uptake values of AMCs were lower than that of [(18) F]FDOPA with S-carbidopa pretreatment, AMCs enabled higher contrast images with lower background activity compared with [(18) F]FDOPA with S-carbidopa pretreatment. Our results indicate the potential uses of these new synthetic amino acids as oncologic radiotracers.

Dental optical coherence tomography: new potential diagnostic system for cracked-tooth syndrome.

PURPOSE: The aim of the present study was to determine the reliability of optical coherence tomography (OCT) in detecting cracked teeth and its relative clinical effectiveness by comparing it with other diagnostic methods including conventional visual inspection, trans-illumination, and micro-computed tomography (micro-CT). METHODS: The reliability of swept source OCT (SS-OCT) was verified by comparing the number of detected crack lines on 109 surfaces of 61 teeth with those detected with other conventional methods. RESULTS: One to one comparison revealed that crack lines that were invisible with naked eyes could be found in SS-OCT images. The detection ability of SS-OCT was superior or similar to those of micro-CT (100.0 %) and trans-illumination. CONCLUSIONS: Crack lines shown in the SS-OCT images had distinct characteristics, and structural crack lines and craze lines could be distinguished in SS-OCT images. Thus, the detection ability of SS-OCT renders it an acceptable diagnostic device for cracked-tooth syndrome.

Nomogram for predicting incomplete cytoreduction in advanced ovarian cancer patients.

OBJECTIVE: Accurately predicting cytoreducibility in advanced-ovarian cancer is needed to establish preoperative plans, consider neoadjuvant chemotherapy, and improve clinical trial protocols. We aimed to develop a positron-emission tomography/computed tomography-based nomogram for predicting incomplete cytoreduction in advanced-ovarian cancer patients. METHODS: Between 2006 and 2012, 343 consecutive advanced-ovarian cancer patients underwent positron-emission tomography/computed tomography before primary cytoreduction: 240 and 103 patients were assigned to the model development or validation cohort, respectively. After reviewing the detailed surgical documentation, incomplete cytoreduction was defined as a remaining gross residual tumor. We evaluated each individual surgeon's surgical aggressiveness index (number of high-complex surgeries/total number of surgeries). Possible predictors, including surgical aggressiveness index and positron-emission tomography/computed tomography features, were analyzed using logistic regression modeling. A nomogram based on this model was developed and externally validated. RESULTS: Complete cytoreduction was achieved in 120 patients (35%). Surgical aggressiveness index and five positron-emission tomography/computed tomography features were independent predictors of incomplete cytoreduction. Our nomogram predicted incomplete cytoreduction by incorporating these variables and demonstrated good predictive accuracy (concordance index = 0.881; 95% CI = 0.838-0.923). The predictive accuracy of our validation cohort was also good (concordance index = 0.881; 95% CI = 0.790-0.932) and the predicted probability was close to the actual observed outcome. Our model demonstrated good performance across surgeons with varying degrees of surgical aggressiveness. CONCLUSION: We have developed and validated a nomogram for predicting incomplete cytoreduction in advanced-ovarian cancer patients which may help stratify patients for clinical trials, establish meticulous preoperative plans, and determine if neoadjuvant chemotherapy is warranted.

Clinical course and prognostic factors in patients with malignant pheochromocytoma and paraganglioma: A single institution experience.

OBJECTIVES: Malignant pheochromocytoma (PCC)/paraganglioma (PG) are rare neuroendocrine malignancies, and their clinical courses and prognoses are not well understood. This study aimed to evaluate prognostic factors associated with the survival of malignant PCC/PG. METHODS: This retrospective study reviewed 299 patients with PCC and 46 with PG treated between 1997 and 2013 at our single tertiary hospital. Malignant PCC/PG was defined as the presence of distant metastasis or recurrence at sites where neuroendocrine tissue is normally not present. RESULTS: Twenty-seven patients (9%) were confirmed with malignant PCC and six patients (13%) with malignant PG. Twenty-seven patients (82%) had distant metastases, nine patients (27%) presented with a metastasis at the initial diagnosis, whilst 24 patients (73%) were diagnosed with malignant PCC/PG during follow-up (median, 4.3 year). The median survival was 7.2 years, and the 5 year survival rate was 75.4%. Older age (>45 years), larger tumor size (>6 cm), synchronous metastasis, and absence of surgical excision were associated with poor survival by univariate analysis. By multivariate analysis, older age (HR = 4.3, P = 0.02) and synchronous metastasis (HR = 4.3, P = 0.01) were significantly associated with a poor prognosis. CONCLUSIONS: Patients with malignant PCC/PG have diverse clinical courses. Poor survival was independently associated with older age and synchronous metastasis.

Simple preparation of new [(18) F]F-labeled synthetic amino acid derivatives with two click reactions in one-pot and SPE purification.

New [(18) F]fluorinated 1,2,3-triazolyl amino acid derivatives were efficiently prepared from Huisgen 1,3-dipolar cycloaddition reactions, well known as click reaction. We developed two simultaneous click reactions in one-pot with a simple solid-phase extraction (SPE) purification method. [(18) F]fluoro-1-propyne was obtained at a 45% non-decay corrected radiochemical yield based on the [(18) F]fluoride ion. The one-pot and simultaneous two click reactions were performed with unprotected azido-alkyl amino acid, [(18) F]fluoro-1-propyne, and lipophilic additive alkyne to produce three synthetic amino acid derivatives, AMC-101 ([(18) F]-6a), AMC-102 ([(18) F]-6b), and AMC-103 ([(18) F]-6c) with 29%, 28%, and 24% of non-decay corrected radiochemical yields, respectively. All radiotracers indicated that radiochemical purities were >95% without any residual organic solvent. Our new method involving two click reactions in one-pot showed high radiochemical and chemical purity by easy removal of the residual precursor from the simultaneous two click reactions.

Diagnostic performance of breast-specific gamma imaging in the assessment of residual tumor after neoadjuvant chemotherapy in breast cancer patients.

To evaluate the diagnostic performance of breast-specific gamma imaging (BSGI) in the assessment of residual tumor after neoadjuvant chemotherapy (NAC) in breast cancer patients, female breast cancer patients who underwent NAC, preoperative (99m)Tc-sestamibi BSGI, and subsequent definitive breast surgery were enrolled retrospectively. The accuracy of BSGI in the assessment of residual tumor presence and residual tumor size was evaluated and compared to that of magnetic resonance imaging (MRI) using pathology results as the gold standard. The sensitivity and specificity of BSGI for residual tumor detection in 122 enrolled patients were 74.0 and 72.2 %, respectively, and were comparable to those of MRI (81.7 and 72.2 %; P > 0.100). The residual tumor size was significantly underestimated by BSGI in the luminal subtype (P = 0.008) and by MRI in the luminal (P < 0.001) and HER2 subtypes (P = 0.032), with a significantly lesser degree of underestimation by BSGI than MRI in both subtypes. In the triple-negative subtype, both BSGI and MRI generated accurate tumor size measurements. The residual cellularity of triple-negative tumors was significantly higher than that of the non-triple-negative tumors (P = 0.017). The diagnostic performance of BSGI in the assessment of residual tumor is comparable to that of MRI in breast cancer patients. The assessment of residual tumor extent by BSGI depends on the molecular subtype, but BSGI may be more accurate than MRI. Underestimation of tumor size in the luminal and/or HER2 subtypes by BSGI and MRI may be due to low-residual cellularity.

Thymidine phosphorylase influences [(18)F]fluorothymidine uptake in cancer cells and patients with non-small cell lung cancer.

PURPOSE: Thymidine phosphorylase (TP), a key enzyme in the pyrimidine nucleoside salvage pathway, catalyses the reversible phosphorylation of thymidine, thereby generating thymine and 2-deoxy-D-ribose-1-phosphate. By regulating the levels of endogenous thymidine, TP may influence [(18)F]fluorothymidine ([(18)F]FLT) uptake. We investigated the effect of TP activity on [(18)F]FLT uptake by tumours. METHODS: Uptake of [(3)H]FLT and [(3)H]thymidine ([(3)H]Thd) and the activities of TP, thymidine kinase 1 (TK1), and equilibrative nucleoside transporter 1 (ENT1) were determined in exponentially growing A431, A549, HT29, HOP92, ACHN, and SKOV3 cells in the presence or absence of tipiracil hydrochloride, a TP inhibitor. Eighty-five non-small cell lung cancer tissues from a patient cohort that was previously studied with [(18)F]FLT positron emission tomography (PET) were retrieved and subjected to immunohistochemical analysis of TP expression. Factors that affected the maximum standardised uptake value (SUVmax) of [(18)F]FLT-PET were identified by multiple linear regression analysis. RESULTS: A431 cells had the highest TP activity; A549 and HT29 cells had moderate TP activity; and ACHN, SKOV3, and HOP92 cells had little detectable TP activity. Cell lines with high TP activity took up more [(3)H]FLT than [(3)H]Thd, whereas cells with little TP activity took up more [(3)H]Thd than [(3)H]FLT. In cells with high TP activity, TP inhibition decreased [(3)H]FLT uptake and increased [(3)H]Thd uptake. However, TP inhibition had no effect on ACHN, SKOV3, and HOP92 cells. TP inhibition did not change TK1 or ENT1 activity, but did increase the intracellular level of thymidine. The SUVmax of [(18)F]FLT was affected by three independent factors: Ki-67 expression (P < 0.001), immunohistochemical TP score (P < 0.001), and tumour size (P = 0.015). CONCLUSIONS: TP activity influences [(18)F]FLT uptake, and may explain preferential uptake of [(18)F]FLT over [(3)H]Thd. These results provide important insights into the biology of [(18)F]FLT as a proliferation marker.