6<Superscript>e</Superscript> Symposium International d’Aromathérapie et Plantes Médicinales (1<Superscript>re</Superscript> partie)

Compte rendu

6^e Symposium International dAromathérapie et Plantes Médicinales (1^re partie)     

Increased circulating regulatory T cells (CD4<Superscript>+</Superscript>CD25<Superscript>+</Superscript>CD127<Superscript>−</Superscript>) contribute to lymphocyte anergy in septic shock patients

Purpose  Sepsis syndrome represents the leading cause of death in intensive care unit. Patients present features consistent with a decline in immune responsiveness potentially contributing to mortality. We investigated whether CD4⁺CD25⁺ regulatory T cells (Treg) participate in the induction of lymphocyte anergy after sepsis. Method  Observational study in septic shock patients and experimental study in mice. Results  We took advantage of the recently described flow cytometric gating strategy using the measurement of CD25 and CD127 expressions for monitoring Treg (CD4⁺CD25⁺CD127⁻Foxp3⁺). In patients the increased circulating Treg percentage significantly correlated with a decreased lympho-proliferative response. In a murine model of sepsis mimicking these observations, the ex vivo downregulation of Foxp3 expression using siRNA was associated with a restoration of this response. Conclusion  The relative increase in circulating Treg might play a role in lymphocyte anergy described after septic shock and represent a standardizable surrogate marker of declining proliferative capacity after sepsis. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Tiotropium Respimat<Superscript>®</Superscript> Versus HandiHaler<Superscript>®</Superscript>: Comparison of Bronchodilator Efficacy of Various Doses in Clinical Trials

Introduction

The long-acting muscarinic antagonist tiotropium bromide is approved in many countries as maintenance therapy for chronic obstructive pulmonary disease (COPD). Tiotropium is available as a dry-powder formulation delivered via HandiHaler^® (18 μg once daily) and is now also approved as an aqueous solution delivered via the Respimat^® Soft Mist? Inhaler (5 μg once daily, 2 puffs of 2.5 µg). Several studies have compared the efficacy of tiotropium HandiHaler (18 μg once daily) with different doses of Respimat. We aimed to compare available bronchodilator efficacy data of once-daily Respimat 1.25, 2.5, 5, 10, 20 µg, and HandiHaler 18 µg to investigate which dose of tiotropium delivered by Respimat is the closest match to tiotropium HandiHaler.

Methods

Evaluation of six clinical trials (duration from 3 weeks to 2–3 years) that included lung function measures (trough forced expiratory volume in 1 s and trough forced vital capacity) as key outcomes.

Results

In the six trials, bronchodilator efficacy of Respimat 5 μg and HandiHaler 18 μg was similar; however, reduced bronchodilator efficacy was observed with lower doses of Respimat (1.25 and 2.5 μg).

Conclusion

These findings support the use of the marketed once-daily dose of Respimat 5 μg for the maintenance treatment of patients with COPD.

Funding

Boehringer Ingelheim.

     

Reliability and Responsiveness of NutriQoL<Superscript>®</Superscript> Questionnaire

Introduction

NutriQoL^® (Nestlé Health Science, Vevay, Switzerland) is a questionnaire developed to assess the health-related quality-of-life (HRQoL) of patients with home enteral nutrition (HEN) irrespective of their underlying condition and route of administration. The aim of this work is assessing the questionnaire’s reliability and responsiveness to change.

Methods

Two cohorts of patients with HEN and their primary caregivers were enrolled to assess reliability and responsiveness, respectively. All participants had to be 18 years of age or older, without mental deterioration (≤3 or 4 errors in the Pfeiffer’s test) and with sufficient functional status (>40 points on Karnovsky’s performance status scale). When the patients’ ability to respond to the questionnaire was impaired due to underlying disease, their caregivers answered on their behalf. NutriQoL was administered in two and three visits to reliability and responsiveness cohorts, respectively. Test–retest reliability and internal consistency were assessed by the intra-class correlation coefficient (ICC) and the Cronbach’s α, respectively. Responsiveness was evaluated by standardized effect size and standardized response mean between basal visit and third visit. Finally, the minimal clinically important difference (MCID) was estimated.

Results

A total of 54 and 86 participants were recruited to the reliability and responsiveness cohort, respectively. Thirty-five caregivers were selected to assess the inter-observer reliability. ICC values confirmed the good reproducibility level (ICC >0.75) of the questionnaire in both “physical functioning and activities of daily living” and “social life” domains and total score. The assessment of internal consistency in both domains of the questionnaire showed good internal consistency in visit 2. ICC showed the excellent agreement level between caregiver and patient in the global NutriQoL score. Finally, patients classified as having a minimal change in their health reported a mean (standard deviation) MCID in NutriQoL score of 0.63 (11.51).

Conclusion

NutriQoL is a reliable and unique instrument to measure the HRQoL in HEN patients. NutriQoL detects changes in the health status of the patient. Nevertheless, further research is needed to determine the full extent of the questionnaire responsiveness.

     

<Superscript>131</Superscript>I-Tositumomab (Bexxar®) <Emphasis Type="Italic">vs.</Emphasis><Superscript>90</Superscript>Y-Ibritumomab (Zevalin®) Therapy of Low-Grade Refractory/Relapsed Non-Hodgkin Lymphoma

Introduction

The American Cancer Society estimated 66,120 new cases of non-Hodgkin lymphoma (NHL) in the USA in 2008. Radioimmunotherapy has been shown in clinical trials to be an effective treatment for refractory/relapsed NHL. The available agents are Bexxar®, a ¹³¹I radiolabeled murine monoclonal antibody and Zevalin®, a ⁹⁰Y radiolabeled murine antibody. Both target CD20 receptors present on the surface of lymphocytes. We present our clinical experience with Bexxar® and Zevalin® in the management of low-grade refractory or relapsed NHL.

Methods

This is a retrospective study (Jan 2000–Jul 2006) of 67 patients with NHL, who were treated with Bexxar® (31 patients, group A) or Zevalin® (36 patients, group B) for refractory/relapsed disease. Group A included 16 men and 15 women, 35–81 years old (average, 59.3?±?13.4). Group B included 27 men and nine women, 36–85 years old (average, 55.4?±?13.8). Therapeutic doses ranged 40–138 mCi (average, 78.1?±?28.2) for Bexxar® and 17–34 mCi (average, 28.8?±?4.37) for Zevalin®.

Results

Objective responses were induced in 22 of the 31 patients (70.9%) in group A and 28 of the 36 patients (77.8%) in group B. Complete response was noted in 11 patients (35.5%), partial response in seven patients (22.6%), and mixed response in four patients (12.9%) in group A. There were five patients (16.1%) with stable disease and four patients (12.9%) with disease progression in the same group. Complete response was noted in 15 patients (41.7%), partial response in nine patients (25%), and mixed response in four patients (11.1%) in group B. There were four patients (11.1%) with stable disease and another four patients (11.1%) with disease progression in the same group. The average decreases at posttherapy nadir were 36.9%?±?0.33 (group A) and 52.6%?±?0.32 (group B) for platelets, 27.8%?±?0.27 (group A) and 34.2%?±?0.38 (group B) for leukocytes, and 4.9%?±?0.15 (group A) and 7.6%?±?0.11 (group B) for hemoglobin. Grades 3 and 4 hematological toxicity occurred in 14 patients (45.2%) treated with Bexxar® and 22 patients (61.1%) treated with Zevalin®, but was reversible.

Conclusion

Our study suggests that clinical practice of Bexxar® and Zevalin® radioimmunotherapy is an effective and safe adjunctive treatment for patients with NHL refractory/relapsed to conventional treatment. However, due to the small number of subjects, it was not possible to determine whether differences in the outcomes or toxicities from the two agents were statistically significant.

     

Randomized Controlled Trial of Hyalobarrier<Superscript>®</Superscript> Versus No Hyalobarrier<Superscript>®</Superscript> on the Ovulatory Status of Women with Periovarian Adhesions: A Pilot Study

Introduction

Periadnexal adhesions are known to contribute to subfertility. The restoration of the tubo-ovarian anatomy is one the key principles in reproductive surgery, and this involves adhesiolysis. However, adhesion formation/reformation is very common after periovarian adhesiolysis. It is not known if the application of Hyalobarrier^®, an anti-adhesion gel, around the adnexal region postsurgery influences ovulatory status. The study is a pilot randomized controlled trial (RCT) randomizing women into the application of Hyalobarrier^® versus no Hyalobarrier^® at the time of laparoscopy, where postsurgical ovulatory status and pregnancy rates were evaluated.

Methods

This was a pilot RCT where women were recruited from the gynecological and subfertility clinic who were deemed to require an operative laparoscopy. If intraoperatively they were found to have periovarian adhesions, they were randomized into having adhesiolysis with and without usage of Hyalobarrier^®. Demographic details and intraoperative details including the severity, extent, and the ease of use of Hyalobarrier^® were recorded. Prior to the surgery and postoperatively, the participants had their serum hormonal status (day 2 FSH, LH and day 21 progesterone) evaluated. Postoperatively, they underwent a follicular tracking cycle at 3 months.

Results

Fifteen women were randomized into use of Hyalobarrier^® (study group) and 15 into the no Hyalobarrier^® group (control group) between December 2011 and January 2014. There was no difference in the patient characteristics in terms of age, BMI, the number of previous pregnancies, or the extent, site, and severity of adhesions between the two groups. There was no significant difference between the study versus control groups in terms of the hormonal profile (day 2 FSH and day 21 progesterone) before or after surgery. The 3-month postoperative day 10–12 follicular tracking findings and endometrial thickness were similar between the study and control groups. Four women were pregnant in the study group (24%) and one in the control group (7%) cumulatively over 2 years.

Conclusion

The use of Hyalobarrier^® post salpingo-ovariolysis did not influence follicular development as inferred from the results of the day 21 progesterone and folliculogram on day 10–12 3-month postsurgery.

Trial Registration

ISRCTN number, ISRCTN1833588.

Funding

Nordic Pharma.

     

<Superscript>123</Superscript>I-BMIPP and <Superscript>99m</Superscript>Tc-TF discordance on myocardial scintigraphy and it’s correlation with functional recovery following acute myocardial infarction: role of conventional echocardiography

¹²³I-β-methyl-iodophenyl pentadecanoic acid (BMIPP) and ^99mTc-Tetrofosmin (TF) mismatch designated as stunned myocardium having both systolic and diastolic components. The degree of mismatch might reflect subsequent functional improvement, and this study was designed to unravel the impact of mismatched defect score (MMDS) on recovery of both systolic and diastolic function following acute myocardial infarction (AMI). Forty patients with recent AMI were recruited, and all of them underwent emergency percutaneous coronary intervention. Echocardiography and BMIPP and TF cardiac scintigraphy were performed on 7 ± 3 days of admission. Follow up echocardiography was performed after 3 months. MMDS were compared with the systolic [ejection fraction (EF) and wall motion score index (WMSI)] and diastolic [peak velocity of early diastolic filling of mitral inflow/peak early diastolic velocity of the mitral annulus(E/E′) and left atrial volume index(LAVI)] parameters. BMIPP defect score was significantly higher than the TF defect score and there was a strong positive correlation between them (r = 0.90, P < 0.00001). Thirty-two (80%) patients showed mismatched defect and rest 8(20%) showed matched defect. Of 32 patients 24(75%), 22(69%), 19(59%), and 20(62.5%) showed improved EF, WMSI, E/E′ and LAVI respectively. Conversely out of 8 only 2(25%), 1(12.5%), and 2(25%) patients showed improvement of EF, WMSI and LAVI, respectively. E/E′ was not improved in patients with matched defect. MMDS were significantly correlated with the improvement of EF (r = −0.46, P = 0.002), WMSI (r = 0.41, P = 0.007), E/E′ (r = 0.56, P < 0.0002), and LAVI (r = 0.44, P = 0.004). Mismatched defect score could predict the approximate amount of viable dysfunctional myocardium, and the degree of mismatch showed a significant correlation with the improvement of both systolic and diastolic function.     

In vitro performance of prefilled CO<Subscript>2</Subscript> absorbers with the Aisys<Superscript>®</Superscript>

Low flow anesthesia increases the use of CO₂ absorbents, but independent data that compare canister life of the newest CO₂ absorbents are scarce. Seven different pre-packed CO₂ canisters were tested in vitro: Amsorb Plus, Spherasorb, LoFloSorb, Medisorb, Medisorb EF, LithoLyme, and SpiraLith. CO₂ (160 mL min^?1) flowed into the tip of a 2 L breathing bag that was ventilated with a tidal volume of 500 mL, a respiratory rate of 10/min, and an I:E ratio of 1:1 using the controlled mechanical ventilation mode of the Aisys ^® (GE, Madison, WI, USA). In part I, canister life of each brand (all of the same lot) was tested with 12 different fresh gas flows (FGF) ranging from 0.25 to 4 L min^?1. In part II, canister life of six canisters each of two different lots of each brand were tested with a 350 mL min^?1 FGF. Canister life is presented as “FCU”, fractional canister usage, the fraction of a canister used per hour, and is defined for the inspired CO₂ concentration (F_ICO₂) that denotes exhaustion. In part III, canister life per 100 g fresh granule content was calculated. FCU decreased linearly with increasing FGF. The relative position of the FCU–FGF curves of the different brands depends on the F_ICO₂ threshold because the exhaustion rate (the rate of rise once F_ICO₂ starts to increase) differs among the brands. Intra-lot variability was 18 % or less. The different prepacks can be ranked according their efficiency (least to most efficient) as follows: Amsorb Plus = Medisorb EF < LoFloSorb < Medisorb = Spherasorb = LithoLyme < SpiraLith (all for an F_ICO₂ threshold = 0.5 %). Canister life per 100 g fresh granule content is almost twice as long when LiOH is used as the primary absorbent. The most important factors that determine canister life of prepacks in a circle breathing system are the chemical composition of the canister, the absolute amount of absorbent present in the canister, and the F_ICO₂ replacement threshold. The use of the fractional canister usage allows cost comparisons among different prepacks. Results should not be extrapolated to prepacks that fit onto other anesthesia machines.     

Prospective Evaluation of Two iStent<Superscript>®</Superscript> Trabecular Stents,One iStent Supra<Superscript>®</Superscript> Suprachoroidal Stent,and Postoperative Prostaglandin in Refractory Glaucoma: 4-year Outcomes

Introduction

This study evaluates long-term outcomes of two trabecular micro-bypass stents, one suprachoroidal stent, and postoperative prostaglandin in eyes with refractory open angle glaucoma (OAG).

Methods

Prospective ongoing 5-year study of 80 eligible subjects (70 with 4-year follow-up) with OAG and IOP ≥ 18 mmHg after prior trabeculectomy and while taking 1–3 glaucoma medications. Subjects received two iStent^® trabecular micro-bypass stents, one iStent Supra^® suprachoroidal stent, and postoperative travoprost. Postoperative IOP was measured with medication and annually following medication washouts. Performance was measured by the proportion of eyes with ≥ 20% IOP reduction on one medication (the protocol-specified prostaglandin) versus preoperative medicated IOP (primary outcome); and the proportion of eyes with postoperative IOP ≤ 15 and ≤ 18 mmHg on one medication (secondary outcome). Additional clinical and safety data included medications, visual field, pachymetry, gonioscopy, adverse events, visual acuity, and slit-lamp and fundus examinations.

Results

Preoperatively, mean medicated IOP was 22.0 ± 3.1 mmHg on 1.2 ± 0.4 medications, and mean unmedicated IOP was 26.4 ± 2.4 mmHg. Postoperatively, among eyes without later cataract surgery, mean medicated IOP at all visits through 48 months was ≤ 13.7 mmHg (≥ 37% reduction), and annual unmedicated IOP was ≤ 18.4 mmHg (reductions of ≥ 30% vs. preoperative unmedicated IOP and ≥ 16% vs. preoperative medicated IOP). At all postoperative visits among eyes without additional surgery or medication, ≥ 91% of eyes had ≥ 20% IOP reduction on one medication versus preoperative medicated IOP. At month 48, 97 and 98% of eyes achieved IOP ≤ 15 and ≤ 18 mmHg, respectively, on one medication. Six eyes required additional medication, no eyes required additional glaucoma surgery, and safety measurements were favorable throughout follow-up.

Conclusion

IOP control was achieved safely with two trabecular micro-bypass stents, one suprachoroidal stent, and postoperative prostaglandin. This microinvasive, ab interno approach introduces a possible new treatment option for refractory disease.

Trial Registration

NCT01456390.

Funding

Glaukos Corporation.

     

Evaluation of left atrial functions by color tissue Doppler imaging in adults with body mass indexes ≥30 kg/m<Superscript>2</Superscript> versus those <30 kg/m<Superscript>2</Superscript>

Evaluation of atrial function has received less attention than that of the ventricle although normal atrial function is required for optimal overall cardiac function. Obesity is associated with increased cardiovascular morbidity and mortality. In this study, we compared left atrial functions in obese adults (body mass index = BMI ≥30 kg/m²) with those in non-obese adults (BMI <30 kg/m²) by color tissue Doppler parameters. There were 37 adults with BMI ≥30 kg/m² (mean age 36 ± 11 years) and 26 adults with BMI <30 kg/m² (mean age 35 ± 5 years). Mean BMI was 38 ± 6 kg/m² in the obese group whereas that was 24 ± 2 kg/m² in the non-obese group. For color tissue Doppler imaging, sample volumes were placed on the mid left atrium at the septum, lateral, inferior, and anterior walls. The peak systolic strain (S _s), peak systolic strain rate (SR_s), peak early diastolic SR (SR_e), peak late diastolic SR (SR_a), peak systolic tissue velocity (TV_s), peak early diastolic TV (TV_e) and peak late diastolic TV (TV_a) values were measured. For each measurement, values in three consecutive cardiac cycles were measured and then averaged. To simplify the analysis, the values at each wall were combined and averaged to obtain mean values. All left atrial systolic function parameters (S _s, SR_s, TV_s) were similar between the groups. In addition, there was no statistically significant difference at left atrial diastolic function parameters (SR_e, SR_a, TV_e, TV_a). We could not find any significant difference between obese and non-obese adults at left atrial functions assessed by color tissue Doppler parameters.     

Gluten and Aluminum Content in Synthroid<Superscript>®</Superscript> (Levothyroxine Sodium Tablets)

Introduction

Inquiries from healthcare providers and patients about the gluten and aluminum content of Synthroid^® (levothyroxine sodium tablets) have increased. The objective of this study was to measure and evaluate the gluten content of the raw materials used in the manufacturing of Synthroid. Additionally, this study determined the aluminum content in different strengths of Synthroid tablets by estimating the amount of aluminum in the raw materials used in the manufacturing of Synthroid.

Methods

Gluten levels of three lots of the active pharmaceutical ingredient (API) and one lot of each excipient from different vendors were examined. The ingredients in all current Synthroid formulations (strengths) were evaluated for their quantity of aluminum.

Results

Gluten concentrations were below the lowest limit of detection (<3.0 ppm) for all tested lots of the API and excipients of Synthroid tablets. Aluminum content varied across tablet strengths (range 19–137 µg/tablet). Gluten levels of the API and excipients were found to be below the lowest level of detection and are considered gluten-free based on the US Food and Drug Administration (FDA) definition for food products. Across the various tablet strengths of Synthroid, the maximum aluminum levels were well below the FDA-determined minimal risk level for chronic oral aluminum exposure (1 mg/kg/day).

Conclusion

These data demonstrate that Synthroid tablets are not a source for dietary gluten and are a minimal source of aluminum.

Funding

AbbVie Inc.

     

<Superscript>68</Superscript>Ga-Chloride PET Reveals Human Pancreatic Adenocarcinoma Xenografts in Rats—Comparison with FDG

Purpose  

The aim of the study was to compare ⁶⁸Ga-chloride with 2-[¹⁸F]fluoro-2-deoxy-d-glucose (FDG) for the imaging of pancreatic xenografts.     

12<Superscript>e</Superscript> Symposium International D’Aromathérapie et des Plantes Meédicinales

Agenda

12^e Symposium International D’Aromathérapie et des Plantes Meédicinales 26–28 mars 2010 Palais des Congrès, Grasse     

Cardiac output monitoring in septic shock: evaluation of the third-generation Flotrac-Vigileo<Superscript>®</Superscript>

Continuous cardiac index (CI) monitoring is frequently used in critically ill patients. Few studies have compared the pulse contour-based device FloTrac/Vigileo^® to pulmonary artery thermodilution (PAC) in terms of accuracy for CI monitoring in septic shock. The aim of our study was to compare the third-generation FloTrac/Vigileo^® to PAC in septic shock. Eighteen patients with septic shock requiring monitoring by PAC were included in this study. We monitored CI using both FloTrac/Vigileo^® and continuous thermodilution (PAC-CI). Hemodynamic data were recorded every hour or every 2 min during fluid challenges. The primary endpoint was the global agreement of all CI-paired measurements determined using the Bland–Altman method adapted to replicated data. We tested the linearity of the bias by regression analysis, and compared the reactivity of the 2 techniques during fluid challenges. A receiver operating characteristic (ROC) curve analysis tested the ability of FloTrac/Vigileo^® to detect concordant and significative CI changes, using PAC-CI as the reference method. Overall, 1,201 paired CI measurements were recorded. The Bland–Altman analysis for global agreement of the 2 techniques showed a bias of ?0.1 ± 2.1 L min^?1 m^?2 and a percentage error of 64 %. The overall correlation coefficient between PAC-CI and FloTrac/Vigileo^® CI was 0.47 (p < 0.01), with r² = 0.22. The area under the curve of the ROC curve for detecting concordant and significant changes in CI was 0.72 (0.53; 0.87). In our study, third-generation Flowtrac-Vigileo^® appears to be too inaccurate to be recommended for CI monitoring in septic shock.     

Does focal incidental <Superscript>18</Superscript>F-FDG PET/CT uptake in the prostate have significance?

Purpose

¹⁸F-FDG PET/CT is used to characterize many malignancies, but is not recommended for localized prostate cancer. This study explores the value of multi-parametric MRI (mpMRI) in characterizing incidental prostate ¹⁸F-FDG uptake.

Methods

Thirty-one patients who underwent ¹⁸F-FDG PET/CT for reasons unrelated to prostate cancer and prostate mpMRI were eligible for this retrospective study. The mpMRI included T2-weighted (T2W), dynamic contrast enhancement (DCE), apparent diffusion coefficient (ADC), and MR spectroscopy (MRS) sequences. Fourteen patients were excluded (n = 8 insufficient histopathology, n = 6 radical prostatectomy before PET), and final analysis included 17 patients. A nuclear medicine physician, blinded to clinicopathologic findings, identified suspicious areas and maximum standardized uptake values (SUVmax) on ¹⁸F-FDG PET/CT. Sector-based imaging findings were correlated with annotated histopathology from whole-mount or MRI/transrectal ultrasound fusion biopsy samples. Positive predictive values (PPVs) were estimated using generalized estimating equations with logit link. Results were evaluated with Kruskal–Wallis and Dunn’s multiple comparisons tests.

Results

The PPV of ¹⁸F-FDG PET alone in detecting prostate cancer was 0.65. Combining ¹⁸F-FDG PET as a base parameter with mpMRI (T2W, DCE, ADC, and MRS) increased the PPV to 0.82, 0.83, 0.83, and 0.94, respectively. All benign lesions had SUVmax < 6. Malignant lesions had higher SUVmax values that correlated with Gleason scores. There was a significant difference in SUVmax per prostate between the Gleason ≥ 4 + 5 and benign categories (p = 0.03).

Conclusions

Focal incidental prostate ¹⁸F-FDG uptake has low clinical utility alone, but regions of uptake may harbor high-grade prostate cancer, especially if SUVmax > 6. Using mpMRI to further evaluate incidental ¹⁸F-FDG uptake aids the diagnosis of prostate cancer.

     

Comparison of [<Superscript>99m</Superscript>Tc]3PRGD<Subscript>2</Subscript> Imaging and [<Superscript>18</Superscript>F]FDG PET/CT in Breast Cancer and Expression of Integrin α<Subscript>v</Subscript>β<Subscript>3</Subscript> in Breast Cancer Vascular Endothelial Cells

Purpose

This study aimed to investigate the value of ^99mtechnetium-three polyethylene glycol spacers-arginine-glycine-aspartic acid ([^99mTc]3PRGD₂) imaging in diagnosis and staging of breast cancer compared with 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) imaging, and to explore the expression of integrin α_vβ₃ in tumor vascular endothelial cells.

Procedures

Forty-two women with suspected breast cancer underwent both [^99mTc]3PRGD₂ imaging and [¹⁸F]FDG imaging. Visual analysis was used to assess primary breast lesion, axillary lymph node, and distant metastasis. The tumor-blood (T/B) ratios from [^99mTc]3PRGD₂ imaging and the maximum standardized uptake value (SUVmax) from [¹⁸F]FDG imaging were analyzed for breast lesions. Integrin α_vβ₃ was analyzed through immunohistochemistry.

Results

Forty-five breast lesions were found (malignant, n?=?38; benign, n?=?7). The sensitivity, specificity, and accuracy of [^99mTc]3PRGD₂ and [¹⁸F]FDG imaging in visual analysis for the breast lesion were 97.4, 87.5, and 95.6 % and 97.4, 71.4, and 93.3 %, respectively (P?>?0.05). For semi-quantitative analysis, no significant difference of the area under the curves (AUC) was found in the imaging using the two radiopharmaceuticals (0.880 and 0.955; Z?=?0.88, P?>?0.05). The sensitivity, specificity, and accuracy for axillary lymph node metastasis with [^99mTc]3PRGD₂ and [¹⁸F]FDG were 78.05, 99.36, and 94.92 % and 85.37, 98.72, and 95.64 %, respectively (P?>?0.05). Nine patients with distant metastases were all detected with the two radiopharmaceuticals. The expression of integrin α_vβ₃ was correlated with [^99mTc]3PRGD₂ uptake (r?=?0.582, P?=?0.001), which were significantly higher in the HER2-positive and stage III–IV patients (P?<?0.05).

Conclusions

The prospective study demonstrated that [^99mTc]3PRGD₂ imaging seems to be valuable for diagnosis of breast cancer and its staging. It may be less sensitive for detecting small lymph node metastatic lesions when compared with [¹⁸F]FDG imaging. Integrin α_vβ₃ in tumor microvessels was associated with the breast cancer subtype and its staging.

     

The Synergistic Effect of Selumetinib/Docetaxel Combination Therapy Monitored by [<Superscript>18</Superscript> F]FDG/[<Superscript>18</Superscript> F]FLT PET and Diffusion-Weighted Magnetic Resonance Imaging in a Colorectal Tumor Xenograft Model

Purpose

Positron emission tomography (PET) and diffusion-weighted MRI (DW-MRI) were used to characterize the treatment effects of the MEK1/2 inhibitor selumetinib (AZD6244), docetaxel, and their combination in HCT116 tumor-bearing mice on the molecular level.

Procedures

Mice were treated with vehicle, selumetinib (25 mg/kg), docetaxel (15 mg/kg), or a combination of both drugs for 7 days and imaged at four time points with 2-deoxy-2-[¹⁸?F]fluoro-D-glucose ([¹⁸?F]FDG) or 3′-deoxy-3′-[¹⁸?F]fluorothymidine ([¹⁸?F]FLT) followed by DW-MRI to calculate the apparent diffusion coefficient (ADC). Data was cross-validated using the Pearson correlation coefficient (PCC) and compared to histology (IHC).

Results

Each drug led to tumor growth inhibition but their combination resulted in regression. Separate analysis of PET or ADC could not provide significant differences between groups. Only PCC combined with IHC analysis revealed the highest therapeutic impact for combination therapy.

Conclusion

Combination treatment of selumetinib/docetaxel was superior to the respective mono-therapies shown by PCC of PET and ADC in conjunction with histology.