Evaluation of cancer therapy with imaging is crucial as a surrogate marker of effectiveness and survival. The unique response patterns to therapy with immune-checkpoint inhibitors have facilitated ...the revision of response evaluation criteria using FDG-PET, because the immune response recalls reactive cells such as activated T-cells and macrophages, which show increased glucose metabolism and apparent progression on morphological imaging. Cellular metabolism and function are critical determinants of the viability of active cells in the tumor microenvironment, which would be novel targets of therapies, such as tumor immunity, metabolism, and genetic mutation. Considering tumor heterogeneity and variation in therapy response specific to the mechanisms of therapy, appropriate response evaluation is required. Radiomics approaches, which combine objective image features with a machine learning algorithm as well as pathologic and genetic data, have remarkably progressed over the past decade, and PET radiomics has increased quality and reliability based on the prosperous publications and standardization initiatives. PET and multimodal imaging will play a definitive role in personalized therapeutic strategies by the precise monitoring in future cancer therapy.
Background
2-
18
F Fluoro-D-deoxyglucose positron emission tomography (FDG-PET) is an appropriate diagnostic procedure for staging lung cancer. However, accurate evaluation of lymph node (LN) ...metastases by PET is controversial owing to false-positive/-negative FDG uptake results. The prognostic significance of both false-negative and false-positive LNs on FDG-PET remains to be determined.
Methods
A total of 235 patients with lung cancer were retrospectively analyzed. Maximum standardized uptake values (SUVmax) of the lymph nodes were compared with pathological LN metastases to correlate PET findings with clinicopathological variables and patients’ outcomes.
Results
When SUVmax ≥ 4 was defined as PET-positive for LN metastasis, sensitivity, specificity, and accuracy were 46.0%, 79.5%, and 72.3%, respectively. False-negative cases and pathological n0 cases were significantly younger, had primary tumors that were smaller or lower SUVmax, and adenocarcinomas compared with false-positive and pathological n
+
cases. The difference in survival time between patients with abnormal FDG uptake in the LN and those without was larger than that between pathological LN metastases and no pathological metastases in patients with adenocarcinoma. Multivariate analysis by the Cox proportional hazard model identified smoker, EGFR/ALK negative and LN positive on PET as significant adverse prognostic factors, rather than pathological n-stage.
Conclusions
Abnormal FDG uptake in the LN is an important prognostic factor. Increased glucose metabolism on FDG-PET appears to be a more efficient postoperative prognostic marker than pathological n-stage in patients with lung cancer.
Abstract
To explore stem-cell-targeted radioimmunotherapy with α-particles in acute myelogenous leukemia (AML), pharmacokinetics and dosimetry of the
211
At-labeled anti-C-X-C chemokine receptor type ...4 monoclonal antibody (
211
At-CXCR4 mAb) were conducted using tumor xenografted mice. The biological half-life of
211
At-CXCR4 mAb in blood was 15.0 h. The highest tumor uptake of 5.05%ID/g with the highest tumor-to-muscle ratio of 8.51 ± 6.14 was obtained at 6 h. Radiation dosimetry estimated with a human phantom showed absorbed doses of 0.512 mGy/MBq in the bone marrow, 0.287 mGy/MBq in the kidney, and <1 mGy/MBq in other major organs except bone. Sphere model analysis revealed 22.8 mGy/MBq in a tumor of 10 g; in this case, the tumor-to-bone marrow and tumor-to-kidney ratios were 44.5 and 79.4, respectively. The stem-cell-targeted α-particle therapy using
211
At-CXCR4 mAb for AML appears possible and requires further therapeutic studies.
The significance of l‐type amino acid transporter (LAT) 1 expression remains unclear in the metastatic process of human neoplasms, whereas experimental studies have demonstrated that LAT1 is ...associated with the metastatic process of cancer cells. We compared the immunohistochemical expression of LAT1 and CD98 between the primary site and a concordant pulmonary metastatic site in 93 cancer patients, all of whom had undergone thoracotomy. LAT1, CD98, Ki‐67 labeling index, vascular endothelial growth factor (VEGF), CD31, and CD34 were analyzed by immunohistochemical staining in the resected tumors of 93 cancer patients: 45 colon cancers; nine breast cancers; eight head and neck cancers; 11 genital cancers; 14 soft‐tissue sarcomas; and six other cancers. The expression of these markers was significantly higher in the metastatic sites than in the primary sites. In total, the positive rates of LAT1, CD98, Ki‐67, VEGF, CD31, and CD34 were 40, 24, 56, 41, 45, and 39%, respectively, in the primary sites and 65, 45, 84, 67, 73, and 61%, respectively, in the metastatic sites. LAT1 expression was closely correlated with CD98 expression, angiogenesis, and cell proliferation. The association between LAT1 and CD98 expression was strongest in the primary and metastatic sites. The present study suggests that overexpression of LAT1 and CD98 has an important role to play in the metastatic process of variable human neoplasms. Moreover, LAT1 expression was significantly correlated with cell proliferation and angiogenesis. (Cancer Sci 2008; 99: 2380–2386)
L‐type amino‐acid transporter 1 (LAT1) plays a key role in cell growth and survival. To determine the prognostic significance of LAT1 in multiple myeloma (MM), we investigated the expression of LAT1 ...and its functional subunit, 4Fc heavy chain (CD98), on myeloma cells by immunohistochemistry in 100 newly diagnosed MM patients. High expression (moderate or strong staining intensity) of LAT1 and CD98 was detected in 56% and 45% of patients, respectively. The LAT1 expression score was positively correlated with Ki‐67 index (r = 0.631, P < 0.001), and there was a statistically significant difference in Durie–Salmon stage between patients with high and low LAT1 expression (P = 0.03). In 43 patients treated with melphalan and prednisolone, the overall response rate was significantly higher in the high LAT1 expression group (60.0%) than in the low LAT1 expression group (17.6%) (P = 0.03). Multivariate analysis confirmed that high expression of LAT1 was a significant prognostic factor for predicting poor overall survival independently from the International Staging System (both P = 0.01). Here, we show that the overexpression of LAT1 is significantly associated with high proliferation and poor prognosis in newly diagnosed MM patients. Thus, LAT1 may be a promising pathological marker for identifying high‐risk MM.
L‐3‐18F‐α‐methyl tyrosine (18F‐FAMT) is amino acid PET tracer with a high specificity for differentiate between malignant and benign lesions. Metabolic response on 18F‐FAMT PET could correctly reflect the tumor response after systemic chemotherapy by PET Response Criteria in Solid Tumors guideline in patients with advanced lung cancer. Our results suggest that metabolic response on 18F‐FAMT PET has a potential for predicting the outcome after first‐line chemotherapy.
Objective
Gamma camera-based measurement of glomerular filtration rate (GFR) with
99m
Tc-diethylenetriaminepentaacetic acid (DTPA) is an established non-invasive measurement of split renal function; ...however, it is not as accurate as the plasma sample method. Therefore, study into improving the accuracy of such method is clinically relevant. The aim of this study was to elucidate the feasibility of gamma camera-based GFR measurement using renal depth evaluated by lateral scan of
99m
Tc-DTPA renography and comparing the results with those of GFR using renal depth measured by CT, and three representative formulas.
Methods
The study population comprised 38 patients (median, 69 years; male 28, female 10; median estimated GFR, 67.4 ml/min) with renourinary disorders. Scintigraphy was performed after intravenous injection of 370 MBq
99m
Tc-DTPA by dynamic data acquisition for 20 min, followed by a bilateral static scan of the abdomen for 3 min. All patients underwent computed tomography (CT) within 2 months from renography. GFR was calculated by renography using renal depth determined in five ways; lateral scan of
99m
Tc-DTPA, CT, and three formulas previously created with using weight, height and age. GFRs were compared with estimated GFR (eGFR). The depth of both kidneys measured as described above was compared and evaluated the laterality of the renal depth.
Results
The median values of GFR calculated with renal depth determined by
99m
Tc-DTPA renography, CT, and the three formulas were 87.3, 83.9, 67.8, 68.3, and 71.5 ml/min, respectively. All of them correlated significantly with eGFR (
r
= 0.734,
r
= 0.687,
r
= 0.728,
r
= 0.726, and
r
= 0.686, respectively), however, no significant difference was observed among five correlation coefficients. Bland–Altman plot revealed that eGFR had error and fixed bias when compared with GFRs calculated using renal depth determined by renography, CT, and Taylor’s formula.
The depth of both kidneys measured by
99m
Tc-DTPA renography was equivalent to that measured by CT, however, those measured by the three formulas were significantly smaller than that measured by
99m
Tc-DTPA renography. The depth of the right kidney was larger than that of the left kidney using all three formulas in all patients. However, CT detected only 66% of patients to have a deeper right kidney than left kidney.
Conclusion
Lateral scanning is a feasible procedure to measure renal depth for accurate and reasonable split GFR measurements using
99m
Tc-DTPA renography.
System l amino acid transporter 1 (LAT1) is highly expressed in various types of human cancer, and contributes to cancer growth and survival. Recently, we have shown that LAT1 expression is closely ...related to the growth and aggressiveness of esophageal cancer, and is an independent marker of poor prognosis. However, it remains unclear whether LAT1 inhibition could suppress esophageal cancer growth. In this study, we investigated the tumor‐suppressive effects of the inhibition of LAT1. Both LAT1 and CD98, which covalently associates to LAT1 on the membrane, were expressed in human esophageal cancer cell lines KYSE30 and KYSE150. Quantitative PCR analysis showed that the expression of LAT1 was much higher than other subtypes of LAT. A selective inhibitor of LAT, 2‐aminobicyclo‐(2,2,1)‐heptane‐2‐carboxylic acid (BCH), suppressed cellular uptake of l‐14C‐leucine and cell proliferation in a dose‐dependent manner. It also suppressed phosphorylation of mammalian target of rapamycin, 4E‐BP1, and p70S6K protein, and induced cell cycle arrest at G1 phase. These results suggest that suppression of both mammalian target of rapamycin signaling and cell cycle progression is involved in BCH‐induced growth inhibition. In tumor‐bearing mice, daily treatment with BCH significantly delayed tumor growth and decreased glucose metabolism, indicating that LAT1 inhibition potentially suppresses esophageal cancer growth in vivo. Thus, our results suggest that LAT1 inhibition could be a promising molecular target for the esophageal cancer therapy.
This paper shows the tumor suppressive effects by the inhibition of LAT1 in esophageal cancer. Inhibition of LAT1 with 2‐aminobicyclo‐(2,2,1)‐heptane‐2‐carboxylic acid (BCH) suppressed cell proliferation, mTOR signaling, and induced cell cycle arrest at G1 phase in esophageal cancer cells. Moreover, daily administration of BCH significantly delayed tumor growth and decreased glucose metabolism in tumor‐bearing mice, suggesting that LAT1 inhibition would be a promising molecular target for the therapy of esophageal cancer.
2-18F Fluoro-d-deoxyglucose (FDG) positron emission tomography (PET) is a relevant diagnostic procedure for staging lung cancer. However, accurate evaluation of lymph node metastases by PET is ...controversial because of false-positive FDG uptake.
A total of 245 patients with lung cancer were retrospectively analyzed. Standardized maximum uptake values (SUVmax) of the primary tumor and lymph nodes were compared to pathologic lymph node metastases to correlate PET findings with clinicopathologic variables and patient outcomes.
The SUVmax values of metastatic lymph nodes were significantly higher than those of lymph nodes without metastases (P = .0036). When SUVmax ≥ 4 was defined as PET positive for metastasis, the sensitivity, specificity, and accuracy were 48.1%, 79.8%, and 73.1%, respectively. Multivariate logistic regression analysis showed that age > 75 years, bilateral hilar FDG uptake, and no lymph node swelling were significant factors related to false-positive lymph node metastases. Smoking status, FDG uptake in the primary tumor, and concurrent lung diseases were not significant factors.
Metastatic lymph nodes show higher FDG uptake than false-positive lymph nodes, and older patient age, bilateral hilar FDG uptake, and no swollen nodes are associated with no metastases. Patients with lymph node metastases have worse survival than those with false-positive FDG-PET findings. However, abnormal FDG uptake in the lymph node is an important prognostic factor.
The evaluation of lymph nodes metastasis on preoperative 2-18F fluoro-d-deoxyglucose (FDG)-positron emission tomography for lung cancer remains to be determined. False-positive lymph nodes were found in 39 of 245 cases and were associated with older patient age, bilateral hilar FDG uptake, and no swollen nodes.
This study aimed to compare the occupational radiation exposure of medical workers between general hospitals and university hospitals.
Radiation exposure data from three hospitals in Hiroshima city, ...including one university hospital and two general hospitals, were collected using personal dosimeters. Monthly radiation doses were analyzed, and the annual sum of radiation exposure dose was calculated for 538 subjects in general hospitals and 1224 subjects in the university hospital. To assess the impact of locality, additional data from Nagasaki University Hospital and Fukushima Medical University Hospital were included for comparative analysis. Professional affiliations, such as doctors, nurses, and radiological technologists, were considered in the evaluation.
The study revealed slight but significant differences in radiation doses between general and university hospitals. In general hospitals, except for radiological technologists, a slightly higher radiation dose was observed compared to university hospitals. Despite the annual increase in the use of medical radiation, the majority of hospital workers in both settings adhered to safety guidelines, with occupational radiation exposure remaining below the limit of detection (LOD). Workers who involved in fluoroscopic procedure, whether at university or general hospitals, had higher radiation doses than those who did not.
The study's primary conclusion is that workers in general hospitals experience a slight but significantly higher radiation dose and a lower percentage below the LOD compared to university hospitals. The observed difference is attributed to the greater workload at general hospitals than at university hospitals, and also may be due to the different nature of university hospital and general hospital. University hospitals, characterized by greater academic orientation, tend to benefit from comprehensive support systems, specialized expertise, and advanced technology, leading to more structured and regulated radiation control. These findings provide a basis for targeted interventions, improved safety protocols.
We conducted a prospective multicenter trial to compare the usefulness of 11C‐methionine (MET) and 18F‐fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying tumor recurrence. ...Patients with clinically suspected tumor recurrence after radiotherapy underwent both 11C‐MET and 18F‐FDG PET. When a lesion showed a visually detected uptake of either tracer, it was surgically resected for histopathological analysis. Patients with a lesion negative to both tracers were revaluated by magnetic resonance imaging (MRI) at 3 months after the PET studies. The primary outcome measure was the sensitivity of each tracer in cases with histopathologically confirmed recurrence, as determined by the McNemar test. Sixty‐one cases were enrolled, and 56 cases could be evaluated. The 38 cases where the lesions showed uptake of either 11C‐MET or 18F‐FDG underwent surgery; 32 of these cases were confirmed to be subject to recurrence. Eighteen cases where the lesions showed uptake of neither tracer received follow‐up MRI; the lesion size increased in one of these cases. Among the cases with histologically confirmed recurrence, the sensitivities of 11C‐MET PET and 18F‐FDG PET were 0.97 (32/33, 95% confidence interval CI: 0.85‐0.99) and 0.48 (16/33, 95% CI: 0.33‐0.65), respectively, and the difference was statistically significant (P < .0001). The diagnostic accuracy of 11C‐MET PET was significantly better than that of 18F‐FDG PET (87.5% vs. 69.6%, P = .033). No examination‐related adverse events were observed. The results of the study demonstrated that 11C‐MET PET was superior to 18F‐FDG PET for discriminating between tumor recurrence and radiation‐induced necrosis.
This prospective multicenter study using positron emission tomography (PET) demonstrated the uptake of 11C‐methionine at a significantly higher sensitivity with brain tumor recurrence after radiotherapy than that of 18F‐fluorodeoxyglucose, based on histopathological evidence. The 11C‐methionine PET can be a useful diagnostic tool for the detection of tumor recurrence, distinguishable from radiation‐induced necrosis after radiotherapy in brain tumors.
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