Thymidine phosphorylase influences [18F]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 [¹⁸F]fluorothymidine ([¹⁸F]FLT) uptake. We investigated the effect of TP activity on [¹⁸F]FLT uptake by tumours.

Methods

Uptake of [³H]FLT and [³H]thymidine ([³H]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 [¹⁸F]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 [¹⁸F]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 [³H]FLT than [³H]Thd, whereas cells with little TP activity took up more [³H]Thd than [³H]FLT. In cells with high TP activity, TP inhibition decreased [³H]FLT uptake and increased [³H]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 [¹⁸F]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 [¹⁸F]FLT uptake, and may explain preferential uptake of [¹⁸F]FLT over [³H]Thd. These results provide important insights into the biology of [¹⁸F]FLT as a proliferation marker.     

Characterization of 18F-FDG uptake in human endothelial cells in vitro.

The contribution of (18)F-FDG uptake by endothelial cells to uptake values measured by PET in various tissues is as yet unclear. We therefore sought to characterize (18)F-FDG uptake in an in vitro model of human endothelial cells. METHODS: Commercially obtained human umbilical vein endothelial cells (HUVECs) were seeded in 6-multiwell plates 48-96 h before incubation with 1-2 MBq (18)F-FDG per well. Radioactivity measurements were performed after washing and mechanical dissolvation of the cellular monolayers. Cellular (18)F-FDG uptake was referred to protein concentration. This experimental protocol was subsequently varied to study the effect of different parameters of interest. Furthermore, radio-thin-layer chromatography was used to identify intracellular (18)F-FDG metabolites. (18)F-FDG uptake in HUVECs was compared with that by a human monocyte-macrophage (HMM) preparation and by glioblastoma cells (GLIOs) under identical experimental conditions. RESULTS: (18)F-FDG accumulated in HUVECs in a time-dependent manner and was trapped mainly as (18)F-FDG-6-phosphate and (18)F-FDG-1,6-diphosphate. Unlabeled glucose and cytochalasin B competitively inhibited (18)F-FDG uptake, whereas phlorizin had no significant effect. Glucose deprivation significantly enhanced (18)F-FDG uptake by a factor of 2.7, whereas sodium depletion had no significant influence. HUVECs treated with vascular endothelial growth factor (VEGF) showed a significant 82% increase in (18)F-FDG accumulation after a 2-h exposure to 50 ng/mL VEGF. (18)F-FDG uptake in HUVECs was significantly higher than that in HMMs and in the range of the uptake values measured in GLIOs. CONCLUSION: (18)F-FDG accumulates in HUVECs by mechanisms analogous to those in neoplastic cells or neurons. VEGF significantly stimulates endothelial (18)F-FDG uptake. The observed differences in (18)F-FDG uptake between HUVECs, HMMs, and GLIOs are difficult to extrapolate to in vivo conditions but stimulate further studies on the contribution of endothelial (18)F-FDG uptake to the overall uptake of that tracer in neoplastic or vascular lesions.     

非小细胞肺癌18F-FDG PET显像与增殖细胞核抗原表达的关系

目的　探讨非小细胞肺癌 (NSCLC)标准摄取值 (SUV)与肿瘤增殖细胞核抗原 (PCNA)表达的关系。方法　 3 0例经术后组织病理检查证实为NSCLC患者于术前行全身1 8F 脱氧葡萄糖 (FDG)PET显像 ,测定SUV ,随访预后 ;手术获得肿瘤标本经常规石蜡切片 ,用免疫组织化学技术检测肿瘤组织PCNA表达 ,计算肿瘤细胞PCNA表达阳性百分数 (即PCNA指数 ) ,取肿瘤周围正常肺组织作对照。结果　正常肺组织肺泡细胞PCNA指数均小于 5 % ,肺癌细胞PCNA指数为 (4 9.49± 2 1.2 4) % ,且PCNA指数与SUV之间具有明显的相关性 (r =0 .82 6,P <0 .0 1) ,PCNA表达高的肺癌细胞有高FDG摄取趋势 ;随SUV及PCNA指数的升高 ,肺癌出现复发或转移的几率升高 ,且与未出现复发或转移者之间差异有显著性 (P <0 .0 1)。结论　SUV可间接评价NSCLC细胞的增殖能力 ,亦可作为评价肺癌患者预后的重要参考指标     

F-18 FDG uptake in endometrial cancer

Endometrial cancer, which is one of the most common malignant gynecologic diseases, was detected by F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in a 60-year-old woman with abdominal distention. FDG PET revealed heterogeneous and marked accumulation in the endometrium, which was thought to represent endometrial cancer. In addition, focal intense accumulation of FDG in both lungs suggestive of lung metastases were noted. Endometrial cancer and lung metastases were confirmed by endometrial biopsy and computed tomography of the chest, respectively.     

Influence of thyroid-stimulating hormone on 18F-fluorodeoxyglucose and 99mTc-methoxyisobutylisonitrile uptake in human poorly differentiated thyroid cancer cells in vitro

Objective  In poorly differentiated thyroid cancer originating from thyroid follicular cells, the ability to concentrate iodine is lost. This makes recurrence undetectable by ¹³¹I whole-body scan. In this situation, other radiopharmaceuticals, such as ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) and technetium-99m-methoxyisobutylisonitrile (^99mTc-MIBI), are used to evaluate recurrence or metastasis. Some reports suggest that ¹⁸F-FDG uptake is increased by thyroid-stimulating hormone (TSH) stimulation. This study aimed to determine the influence of TSH on ¹⁸F-FDG and ^99mTc-MIBI uptake in human poorly differentiated thyroid cancer cells in vitro. Materials and methods  The cells were stimulated with 1000 μU/ml of recombinant human thyroid-stimulating hormone (rhTSH) for 1 day, 3 days, and 5 days. Each cell was incubated with 0.5 MBq/ml-1 MBq/ml of ¹⁸F-FDG or 0.5 MBq/ml-1 MBq/ml of ^99mTc-MIBI for 1 h at 37°C. The uptake of each radiopharmaceutical in the cells was quantified as a percent of whole radioactivity per total viable cell number. The quantification of glucose transporter 1, 2, 3 and 4 mRNA expression was measured using RT-PCR. Results  TSH stimulation increased ¹⁸F-FDG uptake in a time-dependent manner. Following 5 days of rhTSH stimulation, ¹⁸F-FDG uptake was approximately 2.2 times that of the control. The increase in ¹⁸F-FDG uptake following rhTSH stimulation was correlated to the increase in GLUT4 mRNA level. The GLUT1 mRNA level was unchanged. An increased uptake of ^99mTc-MIBI was observed with a pattern similar to that of ¹⁸F-FDG. The ^99mTc-MIBI uptake was approximately 1.5 times that of the control 5 days later. Conclusions  These results suggest that TSH stimulates ¹⁸F-FDG and ^99mTc-MIBI uptake in poorly differentiated papillary thyroid cancer, and therefore ¹⁸F-FDG-PET or ^99mTc-MIBI scans under TSH stimulation may be more accurate than under suppression.     

转染B7-H3基因对前列腺癌细胞摄取^18F—FDG和^18F—FLT的影响

目的研究转染B7同系物3（B7-H3）基因对前列腺癌细胞摄取^18F—FDG和^18F-FLT的影响,并探讨抗B7-H3单克隆抗体（简称单抗）对前列腺癌细胞的作用。方法用细胞计数试剂盒（CCK）-8检测鼠源性前列腺癌RM1细胞和转染B7-H3基因RM1的同种细胞（RM1-B7-H3）培养后0．5、1、2、3、4和5d的吸光度（A）值,并用流式细胞仪测定2种细胞的生长周期。在不同糖浓度（0、5．5和11．0mmol／L）、不同细胞数（每孔5×10^4～5×10^6）、不同摄取时间（20～120min）的条件下,测定2种细胞的^18F—FDG摄取率;并在细胞数为1×10^6、反应时间为100min的条件下行^18F-FLT细胞摄取实验。最后测定给予抗B7-H3单抗4H7后RM1-B7-H3细胞的^18F—FDG细胞摄取率。数据比较行单因素方差分析和两样本t检验。结果RM1-B7-H3细胞培养1、2和3d时的A值分别为1．59±0．23、2．26±0．15和2．01±0．60,较RM1细胞（1．22±0．14、1．10±0．09和1．04±0．15）高（t=3．923、19．228和4．467,均P〈0．01）;其他时间点2组间差异无统计学意义（t=-0．094、0．858、2．000,均P〉0．05）。RM1-B7-H3细胞的G1、S、G2／M期比例分别为（32．96±2．56）％、（39．11±2．57）％和（27．94±0．21）％,S期比例较RM1细胞（32．76±1．90）％高（t=3．442,P〈0．05）。2种细胞^18F—FDG摄取率均随培养基糖浓度的增加而降低,随细胞数和摄取时间的增加而升高。在1．0×10^6细胞、摄取100min时,RM1-B7-H3和RM1细胞的^18F—FDG摄取率分别为（55．07±3．99）％和（44．16±3．60）％,^18F—FLT摄取率分别为（5．25±0．81）％和（3．33±0．64）％,差异均有统计学意义（t=4．977和4．567,均P〈0．01）。给予4H7单抗后RM1-B7。H3细胞的^18F—FDG细胞摄取率为（45．36±2．92）％,较未加单抗组^18F—FDG细胞摄取率低（F=10．001,P〈0．01）。结论转染B7-H3基因能增强前列腺癌细胞的代谢和增殖活性,并提高细胞对^18F—FDG和^18F-FLT的摄取;给予抗B7-H3单抗4H7后,RM1-B7-H3细胞的^18F—FDG细胞摄取率降低。     

18F-FDG maximum standard uptake value predicts PD-L1 expression on tumor cells or tumor-infiltrating immune cells in non-small cell lung cancer

Annals of Nuclear Medicine - Programmed cell death-ligand 1 (PD-L1) is expressed on tumor cells (TC) and tumor-infiltrating immune cells (IC). We conducted a retrospective study to investigate the...     

18F-FDG uptake in breast cancer correlates with immunohistochemically defined subtypes

Objectives

To determine whether a correlation exists between maximum standardized uptake value (SUV_max) on ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) and the subtypes of breast cancer.

Methods

This retrospective study involved 548 patients (mean age 51.6 years, range 21–81 years) with 552 index breast cancers (mean size 2.57 cm, range 1.0–14.5 cm). The correlation between ¹⁸F-FDG uptake in PET/CT, expressed as SUV_max, and immunohistochemically defined subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive and triple negative) was analyzed.

Results

The mean SUV_max value of the 552 tumours was 6.07?±?4.63 (range 0.9–32.8). The subtypes of the 552 tumours were 334 (60 %) luminal A, 66 (12 %) luminal B, 60 (11 %) HER2 positive and 92 (17 %) triple negative, for which the mean SUV_max values were 4.69?±?3.45, 6.51?±?4.18, 7.44?±?4.73 and 9.83?±?6.03, respectively. In a multivariate regression analysis, triple-negative and HER2-positive tumours had 1.67-fold (P?<?0.001) and 1.27-fold (P?=?0.009) higher SUV_max values, respectively, than luminal A tumours after adjustment for invasive tumour size, lymph node involvement status and histologic grade.

Conclusion

FDG uptake was independently associated with subtypes of invasive breast cancer. Triple-negative and HER2-positive breast cancers showed higher SUV_max values than luminal A tumours.

Key Points

? ¹⁸ F-FDG PET demonstrates increased tissue glucose metabolism, a hallmark of cancers. ? Immunohistochemically defined subtypes appear significantly associated with FDG uptake (expressed as SUV _max ). ? Triple-negative tumours had 1.67-fold higher SUV _max values than luminal A tumours. ? HER2-positive tumours had 1.27-fold higher SUV _max values than luminal A tumours.     

18F-FLT体外监测结肠癌细胞早期放射反应

目的 评价18F-脱氧胸腺嘧啶核苷（FLT）监测结肠癌细胞早期放射反应的作用.方法 应用四甲基偶氮唑蓝（MTT）检测并绘制SW480细胞受X线照射后生长曲线,光学显微镜下观察细胞形态变化.流式细胞仪检测照射后肿瘤细胞增殖周期的重新分布.分别于体外细胞以及肿瘤内检测照射前、后细胞摄取18F-FLT的变化.将18F-FLT（0.05±0.01）MBq加入培养液孵育细胞,分别于30,60,90,120 min测定细胞摄取18F-FLT的放射性.经荷瘤裸鼠尾静脉注射18F-FLT（1.90±0.85）MBq（0.25 ml）,60 min后处死动物,切除肿瘤与肌肉、肺、肝等,测定肿瘤与其他脏器摄取放射性比值变化.应用单因素方差分析进行统计学处理.结果 X线照射后,SW480细胞增殖受到明显的抑制,呈剂量依赖性.细胞形态随照射剂量的不同发生不同的变化.照射后细胞周期发生重新分布.10 Gy组,S期细胞百分比24 h从33.23%降至15.19%,72 h后降至12.44%.20 Gy组,S期细胞百分比24 h后从33.23%降至9.24%,72 h后降至5.43%.体外摄取实验发现,注射后60 min,SW480细胞摄取18F-FLT百分比为（5.21±1.60）%,10 Gy照射24 h后下降至（4.27±0.48）%,72 h降至（3.39±0.59）%.20 Gy组：照射后24 h,SW480摄取的放射性百分比下降至（3.41±0.58）%,72 h后降至（1.63±0.49）%.两照射组在72 h内分别下降了34.94%,69.72%（24 h∶F=8.253,P=0.009;72 h∶F=36.715,P＜0.001）.单位质量肿瘤组织摄取的18F-FLT随照射剂量的增加而逐渐降低（10Gy组：F=12.388,P=0.007;20 Gy组：F=16.744,P=0.004）.结论 18F-FLT在结肠癌细胞内的摄取可以快速反映照射治疗后的细胞变化,18F-FLT可能用于检测结肠癌放射治疗早期反应.     

F-18 fluoride uptake in primary breast cancer

Objective

Bone-specific radiotracers are known to accumulate in breast lesions. Tc-99m diphosphonates have been widely studied in differentiating breast lesions. In this retrospective study, we aimed to assess the uptake of the bone-specific PET radiotracer, F-18 fluoride (NaF), in primary breast cancers to determine its sensitivity and to identify any differences in NaF uptake between calcified and non-calcified tumors, histological subtypes, and patients with or without axillary lymphadenopathy.

Methods

NaF positron emission tomography/computed tomography (PET/CT) images of 69 newly diagnosed breast cancer patients were reviewed. F-18 fluoride uptake as maximum standardized uptake value (NaF SUVmax) was measured in the primary tumor, enlarged axillary lymph nodes and contralateral normal/non-tumoral breast tissue. Low-dose CT images were reviewed to locate the primary tumor and grossly assess its calcification and check for ipsilateral axillary lymphadenopathy. Whole body NaF PET/CT images were reviewed to search for bone metastases. Eighteen patients also underwent F-18 fluorodeoxyglucose (FDG) PET/CT study.

Results

The primary breast tumor was clearly seen as focal or diffuse uptake on NaF PET images in 27 of 69 patients (39%) (mean NaF SUVmax: 2.0?±?1.0). In the rest, there was only mild bilateral diffuse breast uptake. When analyzing images per histological subtype (42 patients, 43 tumors), 14 of 31 invasive ductal carcinomas (IDC) (45%) and 3 of 4 ductal carcinoma in situ (DCIS) were visible on PET. Five invasive lobular carcinomas, 2 invasive mammary carcinomas, and 1 mucinous carcinoma were not visible on PET. Mean NaF SUVmax of contralateral normal/non-tumoral breast tissue was 1.0?±?0.4. There was no significant difference in mean NaF SUVmax of primary tumor in cases with and without calcification or with and without axillary lymphadenopathy (p 0.892 and 0.957). There was no correlation between NaF SUVmax and FDG SUVmax values of the primary tumors (r 0.072, p 0.797, Pearson correlation).

Conclusion

NaF PET has relatively low sensitivity in detecting breast cancer. However, abnormal breast uptake on NaF PET requires further evaluation. F-18 fluoride uptake in the primary breast tumor does not seem to be correlated with axillary lymphadenopathy (metastasis potential), gross tumor calcification or metabolic activity of the tumor.

     

18F-FLT体外监测结肠癌细胞早期放射反应

Objective To evaluate whether 18F-fluorothymidine(FLT) can be used to monitor early response to irradiation in colorectal cancer (CRC).Methods SW480 cells were cultured and irradiated with 0, 10, and 20 Gy.Twenty-four hours later, morphological changes, apoptosis, necrosis, proliferation,and cell cycle phases were observed.Uptake of 18F-FLT was measured in these tumors in vitro from 24 h to 72 h after irradiation.The one-way analysis of variance was used to analyze the data.Results Apoptotic and necrotic cells were detected 24 h after radiotherapy.SW480 cells proliferation was significantly delayed after irradiation in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide (MTI) assay.Cell cycle analysis showed that SW480 cells had a decreased fraction of cells in S phase( from 33.23% to 9.24%,then to 5.43% ) and an arrested fraction in G0-G1.After SW480 cells were cultured for60 min, the uptake of 18F-FLT was (5.21 ± 1.60) %; and 24 h after irradiation of 10 Gy, the uptake decreased significantly to (4.27±0.48)% (F=8.253, P=0.009).And 72 h after irradiation, the uptake further decreased significantly to (3.39 ± 0.59) % ( F = 36.715, P＜0.001 ).In tumor tissue, the uptake of 18F-FLT reduced significantly 72 h after radiotherapy (10 Gy:F = 12.388, P = 0.007; 20 Gy:F = 16.744, P = 0.004) and the attenuation degree increased with the radiation dose.Conclusion The uptake of 18F-FLT in SW480 cells or in CRC could reflect the changes of SW480 cells in proliferation, cell cycle re-distribution, cell apoptosis and necrosis.The results suggest that 18F-FLT may be used for monitoring early response to irradiation of CRC.     

18F-FLT体外监测结肠癌细胞早期放射反应

Objective To evaluate whether 18F-fluorothymidine(FLT) can be used to monitor early response to irradiation in colorectal cancer (CRC).Methods SW480 cells were cultured and irradiated with 0, 10, and 20 Gy.Twenty-four hours later, morphological changes, apoptosis, necrosis, proliferation,and cell cycle phases were observed.Uptake of 18F-FLT was measured in these tumors in vitro from 24 h to 72 h after irradiation.The one-way analysis of variance was used to analyze the data.Results Apoptotic and necrotic cells were detected 24 h after radiotherapy.SW480 cells proliferation was significantly delayed after irradiation in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide (MTI) assay.Cell cycle analysis showed that SW480 cells had a decreased fraction of cells in S phase( from 33.23% to 9.24%,then to 5.43% ) and an arrested fraction in G0-G1.After SW480 cells were cultured for60 min, the uptake of 18F-FLT was (5.21 ± 1.60) %; and 24 h after irradiation of 10 Gy, the uptake decreased significantly to (4.27±0.48)% (F=8.253, P=0.009).And 72 h after irradiation, the uptake further decreased significantly to (3.39 ± 0.59) % ( F = 36.715, P＜0.001 ).In tumor tissue, the uptake of 18F-FLT reduced significantly 72 h after radiotherapy (10 Gy:F = 12.388, P = 0.007; 20 Gy:F = 16.744, P = 0.004) and the attenuation degree increased with the radiation dose.Conclusion The uptake of 18F-FLT in SW480 cells or in CRC could reflect the changes of SW480 cells in proliferation, cell cycle re-distribution, cell apoptosis and necrosis.The results suggest that 18F-FLT may be used for monitoring early response to irradiation of CRC.     

Correlation of Glut-1 glucose transporter expression with [18F]FDG uptake in non-small cell lung cancer

Positron emission tomography (PET) with [¹⁸F]2-fluoro-2-deoxy-D-glucose (FDG) may show negative results for bronchioloalveolar lung carcinoma. We investigated the correlation of Glut-1 glucose transporter expression with [¹⁸F]FDG uptake in non-small cell lung cancer. Thirty-two patients with 34 non-small cell lung cancers (7 bronchioloalveolar carcinomas, 23 non-bronchioloalveolar adenocarcinomas, 3 squamous cell carcinomas, and 1 adenosquamous cell carcinoma) were studied. Final diagnoses were established by histology (via thoracotomy) in all patients. [¹⁸F]FDG PET was performed 40 min after i.v. injection of 185 MBq [¹⁸F]FDG. For semi-quantitative analysis of [¹⁸F]FDG uptake, standardized uptake values (SUVs) were calculated. Glut-1 expression was studied in terms of the immunohistochemistry of paraffin sections using anti-Glut-1 antibody to determine the intensity (0-3) of Glut-1 immunoreactivity and percentage of the Glut-1-positive area. Of seven bronchioloalveolar carcinomas, six (85.7%) were negative for the expression of Glut-1, while only one (4.3%) of 23 non-bronchioloalveolar adenocarcinomas was negative (P<0.0001). The percentages of Glut-1-positive area, as well as the SUVs, were significantly lower in bronchioloalveolar carcinomas (n=7) (2.86%lj.56% and 1.25ǂ.75, respectively) than in non-bronchioloalveolar adenocarcinomas (n=23) (54.83%ᆭ.64%, P<0.0001, and 3.94ǃ.93, P=0.001, respectively). The degree of cell differentiation correlated with the percentage of Glut-1-positive area and SUVs in adenocarcinoma of the lung. Correlations between SUVs and the intensity of Glut-1 immunoreactivity were also significant (intensities 0 and 1, n=11, SUV 1.47ǂ.63; intensities 2 and 3, n=23, SUV 4.78DŽ.13; P<0.0001). The percentage of Glut-1-positive area correlated significantly with SUVs (n=34, r=0.658, P<0.01). Overexpression of Glut-1 correlated with high [¹⁸F]FDG uptake. These findings suggest that Glut-1 expression is related to [¹⁸F]FDG uptake in non-small cell lung cancer. Glut-1 expression, as well as [¹⁸F]FDG uptake, correlated with the degree of cell differentiation in adenocarcinomas, and both Glut-1 expression and [¹⁸F]FDG uptake were significantly lower in bronchioloalveolar carcinomas than in non-bronchioloalveolar carcinomas.     

Furosemide diminishes 18F-fluoroethylcholine uptake in prostate cancer in vivo

Purpose

¹⁸F-Fluoroethylcholine (¹⁸F-FECh) is excreted via the urinary system with high activity accumulation in the urinary bladder. Furosemide and oral hydration can be administered concomitantly to reduce urinary activity to provide better detectability of retroperitoneal and pelvic lesions. Currently it is unknown if there is any effect of furosemide on ¹⁸F-FECh uptake in organs, tissues and tumour lesions and the extent to which image quality along the urinary tract may be improved by furosemide.

Methods

We retrospectively analysed 217 ¹⁸F-FECh PET/CT examinations from 213 patients with known prostate cancer (PCa), performed either with oral hydration (109) or furosemide 20 mg together with oral hydration (108). Maximum ¹⁸F-FECh uptake in different organs, tissues, lymph nodes and osseous metastases was quantified in terms of standardized uptake value (SUV) in a volume of interest and compared between the two groups. To characterize the impact of furosemide on lesion detectability a three-point rating scale was used to assess the presence of focal activity spots in the ureters and of perivesicular artefacts.

Results

Patient characteristics and distribution of tumour lesions were well balanced between the two groups. Overall, SUVmax values from normal organs were increased after furosemide compared to the values in patients scanned without furosemide. Significant changes were observed in the salivary glands, liver, spleen, pancreas, kidneys, gluteus muscle and perirenal fat. SUVmax values were significantly decreased after furosemide in lymph node metastases (SUVmax 4.81?±?2.68 vs. 6.48?±?4.22, p?=?0.0006), but not in osseous metastases. Evaluation of image quality along the urinary tract revealed significantly better depiction of the perivesicular space and significantly less focal tracer accumulation in the ureters in patients receiving furosemide, but the number of detected lymph nodes was not significantly different.

Conclusion

Furosemide administration reduced choline uptake in tumour lesions, especially significant in pelvic lymph node metastases. Although furosemide administration improved image quality, optimal image quality may also be obtained by adequate hydration without the risk of diminishing choline uptake in PCa lesions. Therefore a controlled hydration protocol seems more appropriate than administration of furosemide.     

Increased 18F-FDG uptake mimicking thyroid cancer in a patient with Hashimoto's thyroiditis

Ohne Zusammenfassung     

Biodistribution and dosimetry of 18F-EF5 in cancer patients with preliminary comparison of 18F-EF5 uptake versus EF5 binding in human glioblastoma

Purpose

The primary purpose of this study was to assess the biodistribution and radiation dose resulting from administration of ¹⁸F-EF5, a lipophilic 2-nitroimidazole hypoxia marker in ten cancer patients. For three of these patients (with glioblastoma) unlabeled EF5 was additionally administered to allow the comparative assessment of ¹⁸F-EF5 tumor uptake with EF5 binding, the latter measured in tumor biopsies by fluorescent anti-EF5 monoclonal antibodies.

Methods

¹⁸F-EF5 was synthesized by electrophilic addition of ¹⁸F₂ gas, made by deuteron bombardment of a neon/fluorine mixture in a high-pressure gas target, to an allyl precursor in trifluoroacetic acid at 0° then purified and administered by intravenous bolus. Three whole-body images were collected for each of ten patients using an Allegro (Philips) scanner. Gamma counts were determined in blood, drawn during each image, and urine, pooled as a single sample. PET images were analyzed to determine radiotracer uptake in several tissues and the resulting radiation dose calculated using OLINDA software and standard phantom. For three patients, 21 mg/kg unlabeled EF5 was administered after the PET scans, and tissue samples obtained the next day at surgery to determine EF5 binding using immunohistochemistry techniques (IHC).

Results

EF5 distributes evenly throughout soft tissue within minutes of injection. Its concentration in blood over the typical time frame of the study (～3.5 h) was nearly constant, consistent with a previously determined EF5 plasma half-life of ～13 h. Elimination was primarily via urine and bile. Radiation exposure from labeled EF5 is similar to other ¹⁸F-labeled imaging agents (e.g., FDG and FMISO). In a de novo glioblastoma multiforme patient, focal uptake of ¹⁸F-EF5 was confirmed by IHC.

Conclusion

These results confirm predictions of biodistribution and safety based on EF5’s characteristics (high biological stability, high lipophilicity). EF5 is a novel hypoxia marker with unique pharmacological characteristics allowing both noninvasive and invasive measurements.     

F-18 FDG uptake in cutaneous metastases from breast cancer

Cutaneous metastases from internal malignancies are rare with a reported incidence between 0.7% and 10%. Among all malignancies the highest incidence of cutaneous metastasis is seen in breast cancer. We report the detection of distant dermal metastases from breast cancer on F-18 FDG PET imaging. A 73-year-old woman with metastatic left breast cancer was referred for F-18 FDG PET/CT scan, which showed multiple FDG avid lesions along cutaneous and subcutaneous nodules in the posterior neck, bilateral proximal arms, anterior chest wall, and trunk. A punch biopsy of a right lower chest wall lesion revealed invasive ductal carcinoma involving the deep dermis.