Tracer Level Electrophilic Synthesis and Pharmacokinetics of the Hypoxia Tracer [18F]EF5

Purpose  

2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide labeled with [¹⁸F]-fluorine ([¹⁸F]EF5), a promising tracer for tumor hypoxia, has previously been synthesized in low yields and low specific radioactivity. In pharmacokinetic evaluations, in the presence of non-radioactive EF5, a uniform and low background uptake and high in vivo stability of [¹⁸F]EF5 have been demonstrated. Our purpose was to increase the specific radioactivity of [¹⁸F]EF5 to enable to study the pharmacokinetics at trace level.     

Pharmacokinetics of [18F]FETNIM: a potential marker for PET.

18F-labeled fluoroerythronitroimidazole (FETNIM) has been suggested as a marker of tumor hypoxia for use with PET. Our goal was to evaluate the pharmacokinetic properties of [18F]FETNIM in rats and analyze metabolites in human, dog, and rat plasma and urine. Metabolites in liver and tumor homogenates from tumor-bearing rats, as well as the biodistribution of the tracer, were also studied. METHODS: Radio-thin-layer chromatography and digital autoradiography were used to distinguish metabolites from the parent drug in urine and plasma from 8 patients, 3 dogs, and 18 rats, as well as in liver and tumor homogenates from Sprague-Dawley rats bearing 7,12-dimethylbenzanthracene-induced rat mammary carcinoma. Biodistribution of [18F]FETNIM was also studied in rats at 15, 30, 60, 120, and 240 min after tracer injection. RESULTS: Most of the radioactivity in plasma and urine was the unchanged tracer, whereas rat liver homogenates contained almost only metabolites of [18F]FETNIM. None of the species studied showed binding of tracer to plasma proteins. A large variation-3%-70%-in the radioactivity represented by unchanged [18F]FETNIM was found in rat tumor. A negative correlation was found between the percentage of radioactivity represented by unchanged [18F]FETNIM in tumor tissue and tumor uptake (percentage injected dose per gram of tissue) at later times. The highest radioactivity was seen in urine and kidney; the lowest uptake was in fat, cerebellum, and bone matrix. In contrast to matrix, bone marrow had high uptake of 18F. The tumor-to-blood ratio reached a maximum of 1.80 +/- 0.64 at 2 h. CONCLUSION: We conclude that [18F]FETNIM shows low peripheral metabolism, little defluorination, and possible metabolic trapping in hypoxic tumor tissue. These suggest a potential use for this tracer in PET studies on hypoxia of cancer patients.     

Surveillance neuroimaging to detect relapse in childhood brain tumors: a Pediatric Oncology Group study.

PURPOSE: To investigate the prognostic significance of surveillance neuroimaging for detection of relapse among children with malignant brain tumors. PATIENTS AND METHODS: A historical cohort study examined all children who experienced relapse from 1985 to 1999 on one of 10 Pediatric Oncology Group trials for malignant glioma, medulloblastoma, or ependymoma. RESULTS: For all 291 patients (median age at diagnosis, 8.2 years), median time to first relapse was 8.8 months (range, 0.6 to 115.6 months). Ninety-nine relapses were radiographic, and 192, clinical; median time to relapse was 15.7 versus 6.6 months, respectively (P = .0001). When stratified by pathology, radiographic and clinical groups showed differences in median time to relapse for malignant glioma (7.8 v 4.3 months, respectively; P = .041) and medulloblastoma (23.6 v 8.9 months, respectively; P = .0006) but not ependymoma (19.5 v 13.3 months, respectively; P = .19). When stratified by early (< 8.8 months) or late (> or = 8.8 months) time to relapse, 115 early relapses were clinical, and 32, radiographic; for late relapses, 77 were clinical, and 67, radiographic (P = .001). Overall survival (OS) from relapse was significantly longer for radiographic compared with clinical detection (median, 10.8 months; 1-year OS, 46% v median, 5.5 months; 1-year OS, 33%; P = .002), but this trend did not retain significance when analyzed by pathology subgroups. CONCLUSION: Surveillance neuroimaging detects a proportion of asymptomatic relapses, particularly late relapses, and may provide lead time for other therapies on investigational trials. During the first year after diagnosis, radiographic detection of asymptomatic relapse was infrequent. A prospective study is needed to formulate a rational surveillance schedule based on the biologic behavior of these tumors.     

Venous drainage system of the transverse rectus abdominis musculocutaneous flap

The transverse rectus abdominis musculocutaneous (TRAM) flap has been widely used for reconstruction of the breast. Partial loss of the flap is still a problem, however, and venous congestion may cause partial necrosis of the flap. There are few studies of the venous anatomy of the TRAM flap that compares with that of the arterial system, so the aim of this study was to investigate the venous anatomy of the TRAM flap and assess its drainage pathway using venography. A mixture of barium and gelatin were injected through the cutaneous veins such as the superficial inferior epigastric vein (SIEV), the superficial circumflex iliac vein (SCIV), or the perforating branch of the deep inferior epigastric vein (DIEV) in 11 hemiTRAM flaps. Venograms of TRAM flaps were taken, and the venous anatomy evaluated. The study showed that it consisted of the dominant superficial venous system, the SIEV and SCIV, and the secondary deep venous system, and the perforating vein of DIEV (DIEV perforator). In addition, we saw the large communicating veins between the SIEV and DIEV perforator near the umbilicus. We think that these communicating veins, which are considered as the DIEV perforators between the superficial and deep venous system, are an important venous drainage pathway after the TRAM flap has been raised.     

上海市中老年人群睡眠质量和睡眠时间与2型糖尿病患病关系研究

目的 分析睡眠质量和睡眠时间与上海市中老年人群2型糖尿病患病之间的关系。方法 利用2017年上海市社区≥35岁居民2型糖尿病流行病学调查数据,采用限制性立方样条曲线绘制PSQI得分和睡眠时间与2型糖尿病关系的剂量-反应曲线,采用logistic回归模型分析睡眠质量、睡眠时间对2型糖尿病患病的影响,并对睡眠质量和睡眠时间与2型糖尿病患病风险的交互作用进行分析。结果 上海市中老年人PSQI分数为（4.09±0.10）分,睡眠质量差的比例为12.55%（95% CI：10.77～14.58）,睡眠时间为（7.19±0.03）h。PSQI得分与糖尿病患病呈线性关系,睡眠时间与糖尿病患病呈近似“U”形关系。多因素调整后,睡眠质量差（PSQI得分>7分）和睡眠时间过短（睡眠时间<6 h）能显著增加2型糖尿病的患病风险,OR值分别为1.17（95% CI：1.06～1.30）和1.20（95% CI：1.01～1.41）。进一步分层分析结果显示,仅睡眠时间<6 h且睡眠质量差和睡眠时间≥8 h且睡眠质量差者糖尿病患病风险增加,OR值分别为1.30（95% CI：1.12～1.52）和1.79（95% CI：1.04～3.07）。结论 睡眠质量差和睡眠时间过短与糖尿病患病风险密切相关,而睡眠过长只有在伴随睡眠质量差的情况下与糖尿病患病风险相关。     

Malignant nerve sheath tumors of the head and neck: four case studies and review of the literature

Summary Malignant peripheral nerve sheath tumors (MPNST) are very uncommon neoplasms. While the incidence of these lesions is estimated to be 0.001% in a general population, they make up 5-15% of all soft tissue sarcomas in the head and neck region. We present four cases of MPNST in the head and neck. Since certain difficulties were encountered in diagnosis, the importance of clinical evaluation is emphasized. The prognosis for these tumor patients is poor in spite of improvements in diagnostic and therapeutic modalities.     

Expression of glucose transporters in head-and-neck tumors

The expression of glucose transporter genes (GLUTI-4) was studied in 20 head-and-neck tumors of 18 patients. All tumors—16 of which were squamous-cell carcinomas (SCC)—expressed GLUTI and/or GLUT3 mRNA, while detectable levels of GLUT2 or GLUT4 mRNA were not observed. The signals for GLUTI and GLUT3 mRNAs varied markedly throughout the SCC tumor population but no clear relationship with the grade of differentiation was found. The high GLUT expression observed in some tumors was, not associated with amplification or rearrangement of the corresponding genes. Immunohistochemistry of 5 SCCs showed that GLUTI protein was located in tumor-cell membranes in relation to the level of mRNA expression. We conclude that both GLUTI and GLUT3 are involved in basal glucose uptake of extracranial head-and-neck tumors. The increased expression of these high-affinity GLUT isoforms may be related to the growth maintenance of cancer tissue in cases of limited supply of substrate e.g., in poorly vascularized tumor areas.     

Prospective evaluation of <Superscript>18</Superscript>F-FACBC PET/CT and PET/MRI versus multiparametric MRI in intermediate- to high-risk prostate cancer patients (FLUCIPRO trial)

Purpose

The purpose of this study was to evaluate ¹⁸F-FACBC PET/CT, PET/MRI, and multiparametric MRI (mpMRI) in detection of primary prostate cancer (PCa).

Methods

Twenty-six men with histologically confirmed PCa underwent PET/CT immediately after injection of 369 ± 10 MBq ¹⁸F-FACBC (fluciclovine) followed by PET/MRI started 55 ± 7 min from injection. Maximum standardized uptake values (SUV_max) were measured for both hybrid PET acquisitions. A separate mpMRI was acquired within a week of the PET scans. Logan plots were used to calculate volume of distribution (V_T). The presence of PCa was estimated in 12 regions with radical prostatectomy findings as ground truth. For each imaging modality, area under the curve (AUC) for detection of PCa was determined to predict diagnostic performance. The clinical trial registration number is NCT02002455.

Results

In the visual analysis, 164/312 (53%) regions contained PCa, and 41 tumor foci were identified. PET/CT demonstrated the highest sensitivity at 87% while its specificity was low at 56%. The AUC of both PET/MRI and mpMRI significantly (p < 0.01) outperformed that of PET/CT while no differences were detected between PET/MRI and mpMRI. SUV_max and V_T of Gleason score (GS) >3 + 4 tumors were significantly (p < 0.05) higher than those for GS 3 + 3 and benign hyperplasia. A total of 442 lymph nodes were evaluable for staging, and PET/CT and PET/MRI demonstrated true-positive findings in only 1/7 patients with metastatic lymph nodes.

Conclusions

Quantitative ¹⁸F-FACBC imaging significantly correlated with GS but failed to outperform MRI in lesion detection. ¹⁸F-FACBC may assist in targeted biopsies in the setting of hybrid imaging with MRI.