共查询到20条相似文献,搜索用时 31 毫秒
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Abbas H. Panju Ali Danesh Mark D. Minden David J. Kelvin Shabbir M. H. Alibhai 《Supportive care in cancer》2009,17(5):539-546
Goals of work Quality of life (QOL) is significantly impaired in patients with acute myeloid leukemia (AML), and fatigue is the most common
and disabling symptom; effective treatment measures have yet to be found. Cytokines, biomarkers of inflammation, may moderate
both health outcomes, but published data are limited. We looked at the role of cytokines in modulating QOL and fatigue in
an older AML population.
Patients and methods We recruited 34 English-speaking patients (23 men, 11 women) aged 50 or older with AML within 1 year of diagnosis. QOL and
fatigue were assessed with validated questionnaires. Blood was simultaneously drawn for quantitative measurement of a 13-cytokine
panel. Repeat measurements were done 4–6 weeks later (n = 28 patients). Spearman correlations between health measures and cytokine levels were examined at baseline, as were changes
in variables between time points. A potentially clinically important correlation was defined as an r ≥ 0.30.
Results At baseline, potentially clinically important correlations were noted between global QOL and interferon (IFN)-γ (r = −0.376, p = 0.031), interleukin (IL)-2 (r = −0.340, p = 0.053), IL-5 (r = −0.368, p = 0.035), IL-8 (r = −0.312, p = 0.077), and TNF-α (r = −0.326, p = 0.064). A similar correlation was observed between IL-6 and fatigue (r = 0.332, p = 0.059). Between time points, there were no potentially important correlations between changes in global QOL and any cytokine.
However, potentially important correlations with fatigue were seen with both IL-5 (r = 0.344, p = 0.073) and IL-10 (r = 0.326, p = 0.091) between time points.
Conclusions These preliminary data provide support for a larger controlled study of cytokines, fatigue, and QOL in patients with AML. 相似文献
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Bernardine M. Pinto Carolyn Rabin George D. Papandonatos Georita M. Frierson Joseph J. Trunzo Bess H. Marcus 《Supportive care in cancer》2008,16(11):1279-1289
Purpose Although physical activity (PA) adoption improves fitness and psychological well-being among cancer survivors, PA maintenance
has not been examined. This paper presents follow-up of a home-based PA program for women treated for early-stage breast cancer.
Materials and methods Eighty-six sedentary women (mean age = 53.14 years, SD = 9.70) were randomly assigned to a PA or contact control group. The
PA group received a 12-week telephone counseling program to adopt PA. Assessments were conducted at baseline, end-of-intervention
(12 weeks), 6, and 9 months post-baseline.
Results When comparing change from end-of-intervention (12 weeks) between groups, a significant reduction was observed in minutes
of PA at 6 months (t = −2.10, p < 0.05), but there was no decrease in intervention effect at 9 months (t = −0.19, p = 0.84). Similarly, post-intervention reductions in fatigue were lost at 6 months (t = 3.27, p < 0.01), but remained present at 9 months (t = 1.65, p = 0.10). PA group’s fitness improvements were maintained at both follow-ups (t = 1.04, p = 0.30 and t = 0.05, p = 0.96). The previously significant intervention effect on vigor was maintained at 6 months (t = 1.32, p = 0.19) but was significantly reduced at 9 months (t = −2.15, p < 0.05). PA participants were more likely to progress in motivational readiness at 6 (OR = 5.95, 95% CI = 2.30, 15.36) and
9 months (OR = 4.09, 95% CI = 1.69, 9.87); however, group differences in meeting PA guidelines were not maintained.
Conclusion Some positive effects of a home-based PA intervention for breast cancer patients were maintained at 6 and 9 months. 相似文献
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Eylem Sahin Cankurtaran Elvan Ozalp Haldun Soygur Derya Iren Akbiyik Levent Turhan Necati Alkis 《Supportive care in cancer》2008,16(11):1291-1298
Goals of the work This study aimed to compare the effectiveness of mirtazapine and imipramine on not only the distressing symptoms of cancer
patients such as pain, nausea, vomiting, appetite loss, and sleep disturbances but also depressive and anxiety symptoms.
Materials and methods Fifty-three patients with cancer who were diagnosed with major depressive disorder, anxiety disorder, or adjustment disorder
were included. Twenty patients on mirtazapine, 13 patients on imipramine, and 20 patients in the control group without medication
were interviewed during three visits (baseline, third week, and sixth week). Pain, nausea, vomiting, appetite loss, and sleep
disturbances were evaluated with self-assessment single-symptom scales during each visit. The patients were also asked to
complete the Hospital Anxiety Depression Scale (HADS) during each visit.
Main results There were no significant differences among the three visits in the mirtazapine, imipramine, or control groups in terms of
pain, nausea, vomiting, or appetite loss. For the initial, middle, and late insomnia, only the mirtazapine group showed improvements
(p = 0.001, p = 0.001, p = 0.003). There were also significant differences in the mean total (p = 0.03), anxiety (p = 0.003), and depression (p = 0.025) scores of HADS among the three visits for patients taking mirtazapine. There were no significant differences for
HADS scores from the baseline to the end point for patients taking imipramine or control group patients.
Conclusion Our findings suggest that mirtazapine is effective for resolving insomnia as well as anxiety and depressive symptoms in cancer
patients. However, more systematic research, such as placebo-controlled studies, is needed. 相似文献
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Laura Q. Rogers Kerry S. Courneya K. Thomas Robbins James Malone Alison Seiz Lori Koch Krishna Rao 《Supportive care in cancer》2008,16(1):19-27
Purpose Our study purpose was to determine physical activity correlates and barriers among head and neck cancer patients.
Materials and methods Fifty-nine (response rate = 91%) head and neck cancer patients from an academic oncology clinic enrolled in a cross-sectional
study utilizing chart review and self-administered questionnaire.
Results The majority were men (83%) and white (92%) with mean age of 58 ± 12.8 years and mean months since diagnosis of 18.6 ± 51.9.
The strongest bivariate correlates of physical activity included enjoyment (r = 0.41; p = 0.002), symptom index (r = −0.36; p = 0.006), alcohol use (r = 0.36; p = 0.007), task self-efficacy (r = 0.33; p = 0.013), perceived barriers (r = −0.27; p = 0.047), and comorbidity score (r = −0.27; p = 0.042). Stepwise regression demonstrated independent associations with physical activity for enjoyment (β = 0.38; p = 0.002) and symptom index (β = −0.33; p = 0.006; R
2 = 0.28). The most prevalent barriers significantly associated with physical activity included dry mouth or throat (r = −0.32; p = 0.016), fatigue (r = −0.27; p = 0.043), drainage in mouth or throat (r = −0.41; p = 0.002), difficulty eating (r = −0.32; p = 0.015), shortness of breath (r = −0.30; p = 0.024), and muscle weakness (r = −0.29; p = 0.033).
Conclusions Our results showed that the strongest independent correlates of physical activity were social cognitive (i.e., enjoyment)
and treatment-related (i.e., symptom index). Treatment-related activity barriers were frequent and significantly associated
with reduced activity. Efforts to enhance exercise adherence in head and neck cancer patients should focus on optimizing enjoyment
and managing treatment-related barriers. 相似文献
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Rebecca H. Foster Surbhi Kanotra Marilyn Stern Sarah H. Elsea 《Journal of developmental and physical disabilities》2011,23(6):501-514
This study explored educational and occupational goals of mothers caring for a child with Smith-Magenis syndrome (SMS). Data
were collected from 97 mothers (M
age = 41.31 years, SD
age = 9.60) via online survey. Results showed that 63.0% of mothers earned an undergraduate or professional degree, while 55.0%
desired to further their education. Those who gave birth to their first child during young adulthood were more likely to complete
an undergraduate or graduate degree than those who were younger when their first child was born (χ
2 = 34.53, p = .003). Overall, 34.1% reported low occupational satisfaction, while 36.5% reported high satisfaction. Approximately 45%
desired to change occupations. Caregiver well-being, satisfaction, self-efficacy, depressive symptoms, and fatigue together
predicted occupational satisfaction beyond the influence of education obtained or household income (∆R
2 = .28, ∆F(5,74) = 4.93, p = .001). Independently, occupational satisfaction was directly influenced by caregiver satisfaction (B = .23, p = .04) and well-being (B = .09, p = .01). Mothers caring for a child with SMS express distinct challenges in meeting educational and occupational goals while
balancing caregiver demands. Clinical and research implications are discussed. 相似文献
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Goals of work Complementary and alternative medicines (CAM) use among cancer patients is becoming more prevalent; however, our understanding
of factors contributing to patients’ decisions to participate in CAM is limited. This study examined correlates of CAM use
among colorectal cancer (CRC) survivors, an understudied population that experiences many physical and psychological difficulties.
Materials and methods The sample was 191, predominantly white, CRC survivors (mean age = 59.9 ± 12.6) who were members of a colon disease registry
at a NYC metropolitan hospital. Participants completed assessments of sociodemographic characteristics, psychosocial factors
[e.g., psychological functioning, cancer specific distress, social support (SS), quality of life (QOL)], and past CAM use
(e.g., chiropractic care, acupuncture, relaxation, hypnosis, and homeopathy).
Main results Seventy-five percent of participants reported using at least one type of CAM; most frequently reported was home remedies (37%).
Younger (p < 0.01) or female patients (p < 0.01) were more likely to participate in CAM than their older male counterparts. Among psychosocial factors, poorer perceived
SS (p = 0.00), more intrusive thoughts (p < 0.05), and poorer overall perceived QOL (p < 0.05) were associated to CAM use. In a linear regression model (including age, gender, SS, intrusive thoughts, and perceived
QOL), only age remained a significant predictor of CAM use.
Conclusion These findings demonstrate that CAM use is prevalent among CRC survivors and should be assessed routinely by providers. CAMs
may serve as a relevant adjunct to treatment among CRC patients as well as an indication of need for additional SS, especially
among younger patients. 相似文献
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Sonia Ancoli-Israel Lianqi Liu Michelle Rissling Loki Natarajan Ariel B. Neikrug Barton W. Palmer Paul J. Mills Barbara A. Parker Georgia Robins Sadler Jeanne Maglione 《Supportive care in cancer》2014,22(9):2535-2545
Purpose
Sleep disturbance, fatigue and depression are common complaints in patients with cancer, and often contribute to worse quality of life (QoL). Circadian activity rhythms (CARs) are often disrupted in cancer patients. These symptoms worsen during treatment, but less is known about their long-term trajectory.Methods
Sixty-eight women with stage I-III breast cancer (BC) scheduled to receive ≥4 cycles of chemotherapy, and age-, ethnicity-, and education-matched normal, cancer-free controls (NC) participated. Sleep was measured with actigraphy (nocturnal total sleep time [nocturnal TST] and daytime total nap time [NAPTIME]) and with the Pittsburgh Sleep Quality Index (PSQI); fatigue with the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF); depression with the Center of Epidemiological Studies-Depression (CES-D). CARs were derived from actigraphy. Several measures of QoL were administered. Data were collected at three time points: before (baseline), end of cycle 4 (cycle 4), and 1 year post-chemotherapy (1 year).Results
Compared to NC, BC had longer NAPTIME, worse sleep quality, more fatigue, more depressive symptoms, more disrupted CARs, and worse QoL at baseline (all p values <0.05). At cycle 4, BC showed worse sleep, increased fatigue, more depressive symptoms, and more disrupted CARs compared to their own baseline levels and to NC (all p values <0.05). By 1 year, BC’s fatigue, depressive symptoms, and QoL returned to baseline levels but were still worse than those of NC, while NAPTIME and CARs did not differ from NC’s.Conclusion
Additional research is needed to determine if beginning treatment of these symptoms before the start of chemotherapy will minimize symptom severity over time. 相似文献11.
Stacey L. Hart David M. Latini Janet E. Cowan Peter R. Carroll CaPSURE™ Investigators 《Supportive care in cancer》2008,16(2):161-169
Goals of work Fear of cancer recurrence (FOR) is common in prostate cancer patients, but little research has examined the impact of FOR
on quality of life (QOL) or the mechanism by which these fears become intensified. The objective of this study was to examine
treatment satisfaction (TS) as a moderator of the relationship between FOR and QOL.
Patients and methods Data were drawn from the CaPSURE™ database, a 12,000-man national observational prostate cancer registry. Three hundred and
thirty-three patients who underwent radical prostatectomy (RP) to treat their prostate cancer completed self-report measures.
TS was measured 0–6 months post-RP with a nine-item scale developed for this study, FOR was measured 6–12 months post-RP with
a previously validated five-item scale, and QOL was measured 12–18 months post-RP with the Short Form 36.
Main results After controlling for age, education, number of comorbid medical conditions, and cancer severity, lower FOR (B = −0.12, p < 0.0001), higher TS (B = 0.09, p < 0.001), and the interaction of TS × FOR (B = 0.87, p < 0.05) significantly predicted higher mental health QOL scores. Furthermore, lower FOR (B = −0.08, p < 0.01), and the interaction of TS × FOR (B = −1.11, p < 0.01) significantly predicted higher physical health QOL scores.
Conclusions TS levels mitigated the impact of high FOR on lower levels of QOL. Specifically, patients who reported lower TS and greater
FOR endorsed significantly lower levels of QOL compared to other patients in the sample. 相似文献
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Kazuki Sato Mitsunori Miyashita Tatsuya Morita Makiko Sanjo Yasuo Shima Yosuke Uchitomi 《Supportive care in cancer》2008,16(2):113-122
Goals In Japan, most cancer patients die in the hospital. The aim of this study was to assess the quality of end-of-life treatment
for dying cancer patients in general wards and palliative care unit (PCU).
Materials and methods A retrospective chart review study was conducted. The following data on cancer patients who died in general wards (N = 104) and PCU (N = 201) at a regional cancer center were collected: do-not-resuscitate (DNR) decisions, treatments in the last 48 h of life,
and aggressiveness of cancer care for dying patients.
Main results DNR orders were documented for most patients (94% in general wards, 98% in PCU, p = 0.067) and families usually consented (97%, 97%, p = 0.307). Comparison of general wards with PCU showed that, in the last 48 h of life, significantly more patients in general
wards received life-sustaining treatment (resuscitation, 3.8%, 0%, p = 0.001; mechanical ventilation, 4.8%, 0%, p = 0.004), large volume hydration (>1,000 ml/day, 67%, 10%, p < 0.001) with continuous administration (83%, 5%, p = 0.002) and fewer palliative care drugs (strong opioids, 68%, 92%, p < 0.001; corticosteroids, 49%, 70%, p < 0.001; nonsteroidal anti-inflammatory drugs, 34%, 85%, p < 0.001). Regarding aggressiveness of cancer care, patients received a new chemotherapy regimen within 30 days of death (3.0%),
chemotherapy within 14 days of death (4.3%), and intensive care unit admission in the last month of life (3.3%).
Conclusion We found that families, not patients, consented to DNR, and life-sustaining treatments were appropriately withheld; however,
patients on general wards received excessive hydration, and the use of palliative care drugs could be improved. Application
of our findings can be used to improve clinical care in general wards. 相似文献
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Background To clarify the prevalence and severity of the symptoms, 203 consecutive patients with breast, prostate and other cancers treated
mainly for palliation were surveyed.
Materials and methods The series includes 116 men and 87 women with the mean age of 65 years (range 27–86 years). The patients filled-up the Edmonton
Symptom Assessment System (ESAS) questionnaire with 11 items describing cancer-related symptoms in the visual analogue scale
(VAS).
Results Altogether, 98% of the patients reported at least 1 of the 10 symptoms. There was a significant difference in the score frequencies
between the 10 symptoms (p = 0.0001), fatigue receiving the highest frequency (50.8%) of the high scores. Fatigue was also the single most frequent
symptom reported by 86.3% of the patients, followed by pain at effort (71.5%), sleeplessness (71.1%) and depression (59.0%).
The most disturbing syndrome was pain (n = 48, 23.9%), followed by fatigue (n = 28, 13.9%), depression (9.5%) and dyspnoea (6.0%). Altogether, 75% had more than 5 symptoms and 10% reported all 10 symptoms.
The total number of symptoms was not significantly associated with sex (p = 0.781) or age (p = 0.062), but it was associated with the diagnostic group; patients with breast cancer (n = 41) and those with prostate cancer (n = 44) reported fewer symptoms than the patients with other cancers (n = 116)(p = 0.023, Kruskal–Wallis).
Conclusions Symptoms related to cancer are common among patients treated with palliative indication, but if not specifically surveyed,
may remain un-detected and un-treated. ESAS as a clinical tool brings more symptoms to the attention of the physicians and
helps in getting a comprehensive insight into the patient’s problems. 相似文献
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Susan Thompson Aditya Bardia Angelina Tan Debra L. Barton Lisa Kottschade Jeff A. Sloan Brad Christensen DeAnne Smith Charles L. Loprinzi 《Supportive care in cancer》2008,16(1):75-82
Goals of work The objectives of this pilot trial were to assess the potential efficacy and safety of levetiracetam for the treatment of
hot flashes, a major cause of morbidity among breast cancer survivors.
Patients and methods Women, aged 18 years or more, with a history of breast cancer or those who wished to avoid estrogen because of a perceived
increased risk of breast cancer, who were experiencing bothersome hot flashes (more than or equal to 14 times per week, for
more than or equal to 1 month before study entry), were included. During the baseline week, general demographic characteristics,
hot flash information, and quality of life data were obtained. At the beginning of week 2, patients were started on levetiracetam
for a total of 4 weeks. Information about hot flashes, quality of life, and toxicity were collected during these 4 weeks and
compared with the baseline week.
Main results After treatment with levetiracetam for 4 weeks (N = 19), mean hot flash scores (frequency times mean severity) were reduced by 57%, and mean hot flash frequencies were reduced
by 53%, compared to the baseline week; both these reductions were greater than what would be expected with a placebo (20–25%
reduction). There were significant improvements in abnormal sweating (p = 0.004), hot flash distress (p = 0.0002), and satisfaction of hot flash control (p = 0.0001), when comparing data from the fourth week of treatment to the baseline week. Twenty-nine percent of the subjects
did not complete the study because of treatment-related adverse events, with the most frequently reported side effects being
somnolence, fatigue, and dizziness, usually with mild to moderate intensity.
Conclusion The results of this pilot trial suggest that levetiracetam might be an effective therapy for the treatment of hot flashes.
Further data are needed to test this hypothesis, evaluating the efficacy and toxicity of this agent.
Financial Disclosure: None 相似文献
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Elizabeth L. Strevel Colin Newman Gregory R. Pond Martha MacLean Lillian L. Siu 《Supportive care in cancer》2007,15(7):829-840
Goals of work The quality of informed consent in phase I trials is controversial, partially due to gaps in patient understanding. We assessed
an educational DVD’s impact on knowledge and satisfaction in cancer patients newly referred to a phase I clinic.
Materials and methods Forty-nine patients were randomly assigned to view an educational DVD (n = 22) which explained phase I trials or a placebo DVD (n = 27). Patients completed a questionnaire assessing knowledge of phase I studies and satisfaction with the DVD. The blinded
interviewing physician (n = 8) rated the patient’s understanding of phase I trials.
Main results The mean patient age was 56; 61% were male. Patients who viewed the educational DVD were less likely to believe that phase
I trials determine drug efficacy (p = 0.019), more likely to know that phase I drugs have not been thoroughly studied in humans (p = 0.003), and less likely to believe that these agents have proven activity against human cancers (p = 0.008). More patients who viewed the educational DVD agreed/strongly agreed that the DVD provided useful information (p < 0.001), were confident in their knowledge of phase I trials (p = 0.031), felt aided in their decision to enter a phase I study (p = 0.011), and would have more questions for their physicians because of the DVD (p = 0.017). No statistically significant difference in physician perception of patient understanding or phase I trial accrual
was observed between the educational and placebo DVD groups.
Conclusions An educational DVD increased patient knowledge and satisfaction regarding participation in phase I clinical trials. 相似文献
16.
Introduction This study aimed to investigate the effects of educational intervention on nurses’ knowledge, attitudes, and behavioral intentions
regarding supplying artificial nutrition and hydration (ANH) to terminal cancer patients.
Materials and methods A quasi-experimental design was adopted. A structured questionnaire evaluated the effects of educational intervention. From
April to June 2005, 88 nurses were enrolled in the gastroenterology, general surgery, and intensive care unit of Taipei Veterans
General Hospital in Taiwan. The nurses were randomly assigned into experimental and control groups in equal numbers (44 nurses
in each group). After the experimental and control groups completed the pretest, the experimental group participated in a
50-min lecture. Both groups received a post-test 2 weeks after the lecture.
Results This study showed that prior to educational intervention, nurses have possessed experiences of ANH use in routine caring for
terminal cancer patients. However, due to the lack of knowledge about supplying ANH to terminal cancer patients, the nurses
trended toward the negative behavioral intention, although they realized the burdens of ANH in these patients. After educational
intervention, mean scores of knowledge, attitudes and behavioral intentions of the experimental group increased significantly
(z = −5.255, p < 0.001; t = −5.191, p < 0.001; z = −3.274, p ≦ 0.001). Mean score changes of knowledge and attitude between these two groups reached significant differences (t = −7.306, p < 0.001; t = −4.165, p < 0.001), but no significant difference was observed in the mean score change of behavioral intention (z = −1.943, p > 0.05).
Conclusion The educational intervention remarkably improved nurses’ knowledge and attitudes regarding supplying terminal cancer patients
with ANH. As for the changes in the behavioral intentions, it requires long-term moral and ethical training and communication.
The results of this research emphasized the importance of educational interventions, which should be considered seriously
in future reference nursing education program. 相似文献
17.
Marylou Cárdenas-Turanzas María Teresa Carrillo Horacio Tovalín-Ahumada Linda Elting 《Supportive care in cancer》2007,15(3):243-249
Objective To improve the care of cancer patients by understanding the factors associated with the place of death.
Patients and methods We conducted a retrospective study of death certificates registered in Mexico during 2003. Adult cases were included if the
underlying cause of death was cancer, death location was in the Mexico City Metropolitan Area (MCMA), and information was
available on sociodemographic characteristics and place of death (home or medical unit).
Main results Of the 10,561 cases meeting the inclusion criteria, 54% died at home. More women (55%) than men died of cancer and at a younger
age (63 vs 64 years, respectively; p < 0.001). Multivariate analysis indicated that patients diagnosed with leukemia and lymphoma were 3.6 times more likely to
die in hospitals than patients diagnosed with other cancers (p < 0.001). Compared with patients who died at home, patients who died in hospitals were significantly more educated, younger,
and residents of counties with more hospital beds density (p < 0.001, p < 0.001, and p = 0.003, respectively). Certificates for in-hospital deaths were more likely to be signed by other physician or health professional
than were those for at-home deaths (p < 0.001). Cases with usual residency located outside the study area were 27 times more likely to die in hospitals than were
metropolitan-area residents (p < 0.001).
Conclusions Patients dying at home tended to be of older age, less educated, diagnosed with prostate, urinary tract or gastrointestinal
cancers, and residents of the MCMA. Health planners should consider determinants of place of death when allocating hospital
or home-based palliative care units. 相似文献
18.
Christian Wolf Sylvia Boesch Bernhard Metzler Helga Weirich-Schwaiger Thomas Trieb Michael F. H. Schocke 《Molecular imaging and biology》2008,10(1):24-29
Purpose Friedreich ataxia (FRDA) is characterized by GAA expansions in the intron 1 of the frataxin gene correlating with disease
onset and progression as well as cardiac affection. Accordingly, FRDA patients with early disease onset show a clear impairment
of mitochondrial function in the myocardium. The purpose of this study was to investigate cardiac function and high-energy
phosphate metabolism in FRDA patients with late disease onset.
Procedures Using a 1.5 T magnetic resonance scanner, cardiac phosphorus-31 two-dimensional chemical shift imaging was performed in ten
patients (seven male, three female) with a late onset of FRDA and in 35 healthy, male controls. Ejection faction (EF) and
interventricular septum thickness (IST) were determined by echocardiography.
Results The differences in left ventricular phosphocreatine (PCr) to β-adenosine triphosphate (β-ATP) ratios between both groups were
not significant. FRDA patients had increased ISTs (10.8 ± 1.6 vs. 9.7 ± 0.9 mm; p = 0.048), which correlated significantly with the left ventricular PCr to β-ATP ratios (r = −0.644; p = 0.04), and decreased EFs (52.24 ± 7.72% vs. 64.09 ± 4.25%; p = 0.001) compared to normal controls.
Conclusions In contrast to FRDA patients with early disease onset, our patients collective exhibited a normal, probably compensated cardiac
mitochondrial function, whereby IST and EF were mildly altered. 相似文献
19.
Frederick T. Chin Mohammed Namavari Jelena Levi Murugesan Subbarayan Pritha Ray Xiaoyuan Chen Sanjiv S. Gambhir 《Molecular imaging and biology》2008,10(2):82-91
2′-Deoxy-2′-[18F]fluoro-5-ethyl-1-β-d-arabinofuranosyluracil ([18F]FEAU) is a promising radiolabeled nucleoside designed to monitor Herpes Simplex Virus Type 1 thymidine kinase (HSV1-tk) reporter gene expression with positron emission tomography (PET). However, the challenging radiosynthesis creates problems
for being able to provide [18F]FEAU routinely. We have developed a routine method using a commercial GE TRACERlab FX-FN radiosynthesis module with customized
equipment to provide [18F]FEAU. All radiochemical yields are decay corrected to end-of-bombardment and reported as means ± SD. Radiofluorination (33 ± 8%;
n = 4), bromination (85 ± 8%; n = 4), coupling reaction (83 ± 6%; n = 4), base hydrolysis steps, and subsequent high-performance liquid chromatography purification afforded purified [18F]FEAU β-anomer in 5 ± 1% overall yield (n = 3 runs) after ~5.5 h and a β/α-anomer ratio of 7.4. Radiochemical/chemical purities and specific activity exceeded 99%
and 1.3 Ci/μmol (48 GBq/μmol), respectively. In cell culture, [18F]FEAU showed significantly (P < 0.05) higher accumulation in C6 cells expressing HSV1-tk/sr39tk as compared to wild-type C6 cells. Furthermore, [18F]FEAU showed slightly higher accumulation than 9-[4-[18F]fluoro-3-(hydroxymethyl)butylguanine ([18F]FHBG) in cells expressing HSV1-tk (P < 0.05), whereas [18F]FHBG showed significantly higher (P < 0.05) accumulation than [18F]FEAU in HSV1-sr39tk-expressing cells. micro-PET imaging of mice carrying tumor xenografts of C6 cells stably expressing HSV1-tk or HSV1-sr39tk are consistent with the cell uptake results. The [18F]FEAU mouse images also showed very low gastrointestinal signal with predominant renal clearance as compared to [18F]FHBG. The routine radiosynthesis of [18F]FEAU was successfully semiautomated using a commercial module along with customized equipment to provide the β-anomer in
modest yields. Although further studies are needed, early results also suggest [18F]FEAU is a promising PET radiotracer for monitoring HSV1-tk reporter gene expression. 相似文献