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Immunohistochemical analysis of proliferating cell density changes. A, The graph shows the changes of mean proliferating cell density of the control and treated tumors post treatment. There was significant difference in proliferating cell density between control and treatment groups on days 2, 4 and 6 (* = P,0.001). B, Representative KI67-stained sections of the control (C) and treated (T) tumors on days 0, 2, 4 and 6. Brown areas reflect positive staining of proliferating tumor cell. Scale bars: 50 mm. doi:10.1371/journal.pone.0058274.g005
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There is a strong need to assess early tumor response to chemotherapy in order to avoid adverse effects from unnecessary chemotherapy and allow early transition to second-line therapy. This study was to quantify tumor perfusion changes with dynamic contrast-enhanced ultrasound (CEUS) in the evaluation of early tumor response to cytotoxic chemothera...
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Head and neck squamous cell carcinomas (HNSCC) exhibit a small population of uniquely tumorigenic cancer stem cells (CSC) endowed with self-renewal and multipotency. We have recently shown that IL-6 enhances the survival and tumorigenic potential of head and neck cancer stem cells (i.e. ALDHhighCD44high cells). Here, we characterized the effect of...
Citations
... Therefore, it seems plausible that there are associations between chemotherapy response or clinical outcomes and the CEUS features in LABC patients treated with NAC. Quantitative analysis of tumor blood perfusion with CEUS can be used for noninvasive assessment of functional changes in tumors after chemotherapy [19,20,25,26]. Huang et al. [20] used CEUS for quantitative evaluation of breast cancer response to chemotherapy and demonstrated that changes in maximum intensity were significantly associated with good therapeutic responses after two cycles of NAC. ...
... Most of the present studies mainly focused on the value of CEUS for quantitative evaluation of tumor response to chemotherapy [19,20,25,26]. The value of the qualitative parameters of CEUS for evaluating the efficacy of NAC and RFS has not been fully assessed. ...
We aimed to explore the value of contrast-enhanced ultrasound (CEUS) in early prediction of pathologic complete response (pCR) and recurrence-free survival (RFS) in locally advanced breast cancer (LABC) patients treated with neoadjuvant chemotherapy (NAC). LABC patients who underwent CEUS before and during NAC from March 2014 to October 2018 were included and assessed. Logistic regression analysis and the Cox proportional hazards model were used to identify independent variables associated with pCR and RFS. Among 122 women, 44 underwent pCR. Molecular subtype, peak intensity (PEAK) and change in diameter were independent predictors of pCR after one cycle of NAC (area under the receiver operating characteristic curve [AUC], 0.81; 95% CI: 0.73, 0.88); Molecular subtype, PEAK and change in time to peak (TTP) were independently associated with pCR after two cycles of NAC (AUC, 0.85; 95% CI: 0.77, 0.91). A higher clinical T (hazard ratio [HR] = 4.75; 95% CI: 1.75, 12.87; p = 0.002) and N stages (HR = 3.39; 95% CI: 1.25, 9.19; p = 0.02) and a longer TTP (HR = 1.06; 95% CI: 1.01, 1.11; p = 0.02) at pre-NAC CEUS were independently associated with poorer RFS. CEUS can be used as a technique to predict pCR and RFS early in LABC patients treated with NAC.
... Studies have shown that assessing the tumour size by morphological measurement could result in over-or underestimating the tumour response to Zh chemotherapy [3], [4] and that the early response of tumours to therapy is difficult to assess using conventional radiographic modalities [5]. In a preclinical setting [6], it was shown that CEUS demonstrated a reduction of tumour perfusion 2 days after treatment which was 4 days before the difference of tumour sizes became measurable by conventional imaging. Accurate and reproducible techniques to assess changes in tumour vascularity, and therefore tumour response, may be a potential way to improve how we treat patients [7]. ...
Dynamic contrast enhanced ultrasound imaging (DCE-US) may be used to characterise tumour vascular perfusion using metrics derived from time amplitude curves (TAC). Three-dimensional (3D) DCE-US enables generation of 3D parametric maps of TAC metrics that may inform on how perfusion varies across the entire tumour. The aim of this work was to understand the effect of low temporal sampling (i.e., < 1 Hz) typical of 3D imaging using a swept 1D array transducer on the evaluation of TAC metrics and the effect of transducer motion in combination with flow on 3D parametric maps generated using both plane wave imaging (7 angles) and focused imaging. Correlation maps were introduced to evaluate the spatial blurring of TAC metrics. A research ultrasound scanner and a pulse-inversion algorithm were used to obtain DCE-US. 2D (frame rate 10 Hz) and 3D (volume rate 0.4 Hz) images were acquired of a simple wall-less vessel phantom (flow phantom) and a cartridge phantom. Volumetric imaging provided similar TACs to that of the higher 2D sampling rate. Varying sweep speed and acceleration/deceleration had little influence on the 3D TAC compared to 2D for both focused and plane wave imaging. Sweeping motion and limited temporal sampling (0.4 Hz) did not change the spatial correlation of TAC metrics measured using focused imaging whereas a small increase in correlation across the cartridge phantom was observed for plane wave imaging. This was attributed to grating lobe artefacts, broad beam spatial blurring and incoherent compounding caused by motion. Increased correlation will reduce the spatial resolution with which inhomogeneity of vascular perfusion can be mapped supporting the choice of focused imaging for DCE-US.
... Therefore, it seems plausible that there are associations between chemotherapy response or clinical outcomes and the CEUS features in LABC patients treated with NAC. Quantitative analysis of tumor blood perfusion with CEUS can be used for noninvasive assessment of functional changes in tumors after chemotherapy [19][20][25][26][27]. Huang et al. [27] used CEUS for quantitative evaluation of breast cancer response to chemotherapy, and demonstrated that changes in maximum intensity was signi cantly associated with good therapeutic responses after two cycles of NAC. ...
... Therefore, it seems plausible that there are associations between chemotherapy response or clinical outcomes and the CEUS features in LABC patients treated with NAC. Quantitative analysis of tumor blood perfusion with CEUS can be used for noninvasive assessment of functional changes in tumors after chemotherapy [19][20][25][26][27]. Huang et al. [27] used CEUS for quantitative evaluation of breast cancer response to chemotherapy, and demonstrated that changes in maximum intensity was signi cantly associated with good therapeutic responses after two cycles of NAC. Our results strengthened the evidence and showed that PEAK was independently associated with pCR even after one cycle of NAC. ...
... TTP as a quantitative parameter of CEUS was suggested to be an independent predictive factor of pCR [27]. Our results showed that ΔTTP is not only associated with pCR after one and two cycles of NAC, but also independently associated with pCR after two cycles of NAC. ...
Background
Contrast-enhanced ultrasound (CEUS) is a promising tool and can facilitate dynamic observation and quantification of tumor perfusion without exposing the patients to any risk of radiation. This preliminary study aimed to investigate the value of CEUS in early predicting pCR and RFS in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy (NAC).
Methods
In this retrospective interpretation of prospective data study, consecutive women with LABC who underwent CEUS examination pre-NAC and after one or two cycles of NAC from March 2014 to October 2018 were included. Written informed consent was obtained from all patients. CEUS qualitative parameters before NAC and quantitative parameters (peak intensity, PEAK; time to peak, TTP; regional blood volume, RBV; regional blood flow, RBF, and mean transit time, MTT) during NAC and their changes were assessed. The relative changes in CEUS parameters and tumor diameter after one and two cycles of NAC were describe as ΔA1 and ΔA2, respectively. Multivariate logistic regression analysis was performed to identify independent variables associated with pCR. Cox proportional hazards model and Kaplan-Meier analysis were used to investigate the independent variables of CEUS and clinical-pathologic factors with RFS.
Results
Among 122 patients (mean age, 51years), 44 (36.1%) underwent PCR. Logistic regression analysis showed that molecular subtype, PEAK1 and △diameter1 were the best predictors of pCR after one cycle of NAC (area under the receiver operating characteristic curve [AUC], 0.81; 95%CI: 0.73, 0.88); Molecular subtype, PEAK2 and △TTP2 were independently associated with pCR after two cycles of NAC (AUC, 0.85, 95% CI: 0.77, 0.91). After 63 months of median follow-up, there were 17 recurrences. Multivariable Cox proportional hazards analysis revealed that a higher clinical T (hazard ratio [HR] = 4.75; 95% CI: 1.75, 12.87; P = 0.002) and N stages (HR = 3.39; 95% CI: 1.25, 9.19; P = 0.02), and a longer TTP (HR = 1.06; 95% CI: 1.01,1.11; P = 0.02) at pre-NAC CEUS were independently associated with poorer RFS.
Conclusions
CEUS can be used as a noninvasively functional technique to early predict pCR as well as RFS in breast cancer patients treated with NAC.
... Ultrasound imaging (US): US have high sensitivity for measuring tumor vasculature and blood flow. Tumor perfusion rates can be measured within a field of view by acoustically bursting the bubbles and then calculating the time spent to repopulate and regain contrast 218 . ...
... reported that chemotherapy using cytotoxic agents decreases tumor MVD. [25] e element flow velocity in a capillary is proportional to the fourth power of the radius and inversely proportional to length. [26] Changes in MVD can influence capillary flow velocity. ...
... e pathophysiologic mechanism for changes in tumor perfusion following chemotherapy is probably associated with the requirements associated with microvessel changes. [25] In our study, the necrotic rate was significantly higher in the responder group than in the non-responder group. It is known that the response to chemotherapy causes cytotoxic tumor cell death resulting in reduced concentrations of tissue endothelial growth factor and therefore apoptosis of immature endothelial cells, with secondary vascular shutdown. ...
... However, it has been demonstrated that cytotoxic chemotherapy induces changes in MVD at an early point. [25] Further prospective and clinical investigations are mandatory to confirm the validity of k value in DCE-US for the early assessment of tumor response to systemic chemotherapy. ...
Objectives
The objective of the study is to determine a parameter on the time-intensity curve (TIC) of dynamic contrast-enhanced ultrasonography (DCE-US) that best correlates with tumor growth and to evaluate whether the parameter could correlate with the early response to irinotecan in a rat liver tumor model.
Material and Methods
Twenty rats with tumors were evaluated (control: Saline, n = 6; treatment: Irinotecan, n = 14) regarding four parameters from TIC: Peak intensity (PI), k value, slope (PI × k), and time to peak (TTP). Relative changes in maximum tumor diameter between day 0 and 10, and parameters in the first 3 days were evaluated. The Mann-Whitney U-test was used to compare differences in tumor size and other parameters. Pearson’s correlation coefficients (r) between tumor size and parameters in the control group were calculated. In the treatment group, relative changes of parameters in the first 3 days were compared between responder and non-responder (<20% and ≥20% increase in size on day 10, respectively).
Results
PI, k value, PI × k, and TTP significantly correlated with tumor growth ( r = 0.513, 0.911, 0.665, and 0.741, respectively). The mean RC in k value among responders ( n = 6) was significantly lower than non-responders ( n = 8) (mean k value, 4.96 vs. 72.5; P = 0.003).
Conclusion
Parameters of DCE-US could be a useful parameter for identifying early response to irinotecan.
... С этой точки зрения актуальной является разработка методов, позволяющих прогнозировать ответ опухоли на лекарственную терапию в короткие сроки после ее начала. Стандартная на сегодняшний день оценка изменений новообразования по критериям RECIST имеет существенные ограничения, поскольку структурная визуализация отражает только изменения размеров опухоли, но не ее биологическую активность [13][14][15]. ...
... Существуют данные, что гибель опухолевой ткани в результате воздействия цитотоксических агентов может оказывать влияние на опухолевый неоангиогенез [18,19]. Для определения перфузии сосудов опухоли в настоящее время применяются такие методы, как ПЭТ, МРТ и КТ с динамическим контрастным усилением, маммосцинтиграфия, УЗИ с контрастным усилением [15,[20][21][22][23], которые требуют введения контрастных веществ, использования радиофармацевтических препаратов и являются относительно дорогостоящими для повторного использования. Для сравнения, ультразвуковая допплерография -это неинвазивный, более доступный и менее затратный метод визуализации, который можно безопасно использовать для повторных измерений. ...
Background. Over the past 20 years, there has been a change in approaches to the treatment of breast cancer, in particular, a significant increase in the role of drug therapy. Breast cancer response to neoadjuvant chemotherapy is currently considered as a surrogate biomarker, which allows evaluation of the clinical course and prognosis of the disease. To solve this problem, it is necessary to assess the functional and metabolic changes in tumor tissue during treatment. Doppler ultrasound is a non-invasive, affordable, and low-cost imaging technique that can be safely used for repeated measurements.
The purpose of the study was to study vascular changes in the tumor by power Doppler ultrasound for the evaluation of the early breast cancer response to neoadjuvant chemotherapy.
Material and Methods . From May 2017 to August 2019, 63 patients with breast cancer received neoadjuvant chemotherapy. Changes in the tumor blood flow were assessed before starting the treatment and prior to the second course of neoadjuvant chemotherapy using Doppler scanning. Changes in tumor blood floor after chemotherapy were compared with the pathological tumor response after surgical treatment.
Results. In the vast majority of cases (78 %), there was a decrease in the number of tumor vessels after the first cycle of neoadjuvant chemotherapy independent of the grade of pathological response. In 8 cases with increased vascularization after the first cycle of neoadjuvant chemotherapy, histological examination of the removed tumor showed no response / weak response to treatment in the absence of peritumoral inflammation. In 5 cases, a sharp increase in the number of vessels around large areas of intranodular necrosis and peritumoral inflammation was observed. In general, a comparison of changes in tumor vascularization and pathological response revealed a weak, although statistically significant, negative correlation between changes in the tumor blood flow after neoadjuvant chemotherapy and pathological response.
Conclusion . It was not possible to establish an unambiguous relationship between the reaction of the vascular bed and the tumor response to the cytostatic effect. An increase in the number of tumor vessels in the absence of peritumoral inflammation was the only situation when changes in tumor blood flow during chemotherapy can be unambiguously interpreted as a predictive criterion for the absence / weak response of the tumor to treatment.
... , Yu et al. ayant notamment montré que les modifications de perfusion après un cycle de CNA s'avéraient être très modérés et sûrement trop précoces pour prédire à elles seules la réponse histologique tumorale[82]. angiogénèse tumorale[84] avec des résultats corrélés à ceux de la perfusion tumorale évaluée en IRM dynamique[85]. L'intérêt de l'échographie de contraste dans l'évaluation précoce de la réponse à la CNA n'a fait que croître ces dernières années et présente des résultats encourageants[86,87]. Cette technique a également pour avantage d'être moins onéreuse, d'avoir une meilleure disponibilité et une meilleure résolution temporelle. ...
La chimiothérapie néoadjuvante (CNA) est un traitement fréquemment proposé aux patientes présentant des tumeurs mammaires localement avancées ou volumineuses au diagnostic. L’obtention d’une réponse histologique complète (pCR) à l’issue de la CNA est un facteur de bon pronostic lié à une diminution du risque de récidive, c’est pourquoi, sa prédiction est devenue un objectif clé pour l’orientation de nouvelles stratégies thérapeutiques. Des études ont montré que les modifications précoces du métabolisme glucidique, évaluées par Tomographie par Émission de Positons (TEP) au 2-desoxy-2-18F-fluoro-D-glucose (18F-FDG) réalisée avant traitement et après une cure de CNA, permettaient au moins partiellement de prédire cette réponse. Toutefois, compte tenu de la diversité des cancers du sein et de la complexité des mécanismes qui sous-tendent à la réponse tumorale, il s’avère nécessaire d’avoir une approche multiparamétrique. Or, la TEP au 18F-FDG, qui est un examen de référence en imagerie médicale pour quantifier le métabolisme et la viabilité des tumeurs cancéreuses, permet également d’appréhender la perfusion tumorale sous couvert d’une imagerie dynamique acquise immédiatement après administration du radiotraceur. Par ailleurs, l’étude de l’hétérogénéité tumorale, métabolique comme perfusionnelle, permet d’obtenir une caractérisation toujours plus poussée des lésions. L’objectif de cette thèse a donc été d’évaluer l’apport combiné du métabolisme et de la perfusion tumorale évaluée par la TEP au 18F-FDG réalisée avant traitement, pour la prédiction de la réponse à la CNA, en l’associant également à d’autres paramètres cliniques et biologiques ainsi qu’à des paramètres de texture caractérisant l’hétérogénéité tumorale. Les études ont été réalisées à l’aide d’une cohorte de 246 patients. Dans une première analyse nous avons évalué l’impact que pourraient avoir différentes méthodes de calcul des indices de texture sur leurs relations avec la réponse à la CNA. Les résultats ont ainsi permis d’identifier qu’une discrétisation relative (DR) de l’image semble plus appropriée pour identifier les patientes bonnes répondeuses. Dans une seconde étude, les relations entre les paramètres d’hétérogénéité tumorale avec les caractéristiques biologiques et moléculaires des tumeurs ont été évaluées. Les résultats ont montré une perfusion tumorale maximale significativement plus élevée pour les tumeurs de stade T3 et T4 et également chez les patients présentant un envahissement métastatique lymphatique régional (N+), sans qu’aucune différence métabolique significative ne soit observée. Par ailleurs, une différence significative d’hétérogénéité de perfusion a été notée entre les phénotypes tumoraux bien qu’aucune différence de perfusion globale n’ait été constatée. Enfin, une analyse de la prédiction de la réponse histologique à la CNA a été réalisée dans une dernière étude, à l’aide de modèles pronostiques utilisant la régression logistique et une sélection de variable univariée. Les meilleures performances de prédiction ont été notées pour les modèles combinant les paramètres cliniques et métaboliques (conventionnels et de texture), les résultats de perfusion ne permettant pas, a priori, d’améliorer la prédiction.
... Due to the rapid development of medical imaging, CEUS has been used widely in China since 2004 and is currently used to diagnose patients with BC (11,12). CEUS is able to characterize mass lesions, stage invasive cancer, eval-o characterize mass lesions, stage invasive cancer, eval-characterize mass lesions, stage invasive cancer, evaluate tumor perfusion in real time with minimal invasiveness, detect tumor recurrence and predict the tumor response to neoadjuvant chemotherapies in BC (13)(14)(15). Diffusion-weighted imaging (DWI) is a sensitive but nonspecific modality able to detect locoregional or metastatic BC disease (16). Diffusion-weighted magnetic resonance imaging (DW-MRI) is able to differentiate between benign and malignant focal hepatic lesions (17). ...
... Previous studies have indicated that CEUS and DW-MRI are successful at identifying BC; however, few studies have investigated the combined use of the two methods to diagnose BC (10)(11)(12)(13)(14). To identify a more effective approach for the diagnosis of BC, combined CEUS and DW-MRI were used in the present study. ...
The present study aimed to investigate the diagnostic and prognostic values of contrast‑enhanced ultrasound (CEUS) combined with diffusion‑weighted magnetic resonance imaging (DW‑MRI) in different subtypes of breast cancer (BC). CEUS and DW‑MRI were conducted in 232 patients with BC prior to surgical treatment. Patients were categorized as having the luminal A subtype, the luminal B subtype, triple‑negative subtype or the human epidermal growth factor receptor 2 (Her‑2)‑positive subtype according to their expression of the estrogen receptor (ER), progesterone receptor (PR) and Her‑2, as detected by immunohistochemistry. The CEUS and DW‑MRI parameters of patients with different subtypes of BC were obtained and analyzed. The risk factors for the prognosis of patients with different subtypes of BC were analyzed using Kaplan‑Meier and COX regression analyses. The diagnostic accuracy rate of CEUS combined with DW‑MRI (93.10%) was higher than that of CEUS (88.79%) or DW‑MRI (82.33%) alone. The local recurrence rate and distant metastasis rate of the Her‑2‑positive subtype were the highest among all the subtypes. Furthermore, patients with Her‑2‑positive BC exhibited a higher proportion of lesions with indistinct margins and histological grade III. Lymph node metastasis and BC subtype were independent risk factors for the prognosis of BC. The overall survival and disease‑free survival of patients with the luminal A subtype were higher than those of patients with the Her‑2‑positive subtype. The results of the current study therefore indicate that CEUS combined with DW‑MRI is more effective at diagnosing the different subtypes of BC than either CEUS or DW‑MRI alone.
... The greatest longitudinal, transverse and anteroposterior dimensions of tumors were measured in gray-scale images using calipers before contrast agent injection. Tumor volume was calculated using the formula for a prolate ellipsoid: volume = π/6 × length × width × depth (Lunt et al. 2011;Wang et al. 2013;Zhou et al. 2011). ...
... Contrast-enhanced ultrasound is a well-known functional imaging technique enabling quantitative assessment of solid tumor perfusion responses to VDAs, both in animals (Tranquart et al. 2008;Wang et al. 2013) and in clinical studies (Lassau et al. 2011). Previous studies focused mostly on perfusion of the entire tumor. ...
Combretastatin A4 phosphate (CA4P) is a vascular disrupting agent that rapidly shuts down blood supply to tumors. Early monitoring of tumor perfusion plays a crucial role in determining the optimal strategy to managing treatment and guiding future therapy. The aim of this study was to investigate the potential value of dynamic contrast-enhanced ultrasound (CEUS) in quantitative evaluation of tumor perfusion at an early stage in CA4P therapy. Central and peripheral perfusion of tumors was detected by CEUS pre-treatment (0 h) and 2, 12 and 48 h after CA4P injection. Two perfusion parameters, maximum intensity (IMAX) and time to peak (TTP), were calculated from the time-intensity curve. After CEUS, the efficacy of CA4P was immediately confirmed by immunofluorescence assay and hematoxylin and eosin, Hoechst 33342 and fluorescein isothiocyanate-lectin staining. In CEUS of the center region of tumors, IMAX gradually decreased from 0 to 12 h and regrew at 48 h (p < 0.01). TTP increased only at 2 h. In the peripheral regions, IMAX did not change obviously from 0 to 12 h (p > 0.05) and just increased at 48 h (p < 0.01). The TTP of peripheral regions had the same tendency to vary tendency as that of center regions. In addition, microvascular density (MVD), vascular perfusion and necrotic area of the tumor were quantitatively analyzed. A close correlation between IMAX and MVD was observed in the center areas of tumors (r = 0.72, p < 0.01), whereas the correlation between IMAX and MVD in peripheral areas was weak (r = 0.37, p < 0.01). However, IMAX was positively correlated with tumor perfusion in both center and peripheral areas of tumors (r = 0.82, p < 0.01, and r = 0.63, p < 0.01, respectively). Consequently, IMAX was a reliable indicator of tumor perfusion evaluation by CEUS. The use of CEUS to quantify tumor perfusion could a promising method for the early detection of tumor responses in anti-vascular treatment.
... Early assessment of response to chemotherapy may also prevent unnecessary toxicity and minimize cost of ineffective treatment, enabling the tailoring of treatment regimens to individual patients. 6,7 Given the importance of being able to specifically image apoptosis, several potential imaging probes have been developed; however, no apoptosis positron emission tomography (PET) imaging agent has been approved for clinical use. Previously studied agents labeled with positron-emitting radionuclides include annexin V, 5,8 synaptotagmin I, 9 caspase-3 inhibitors based on isatins, 10 [ 18 F]-C-SNAT, 11 as well as hydrophobic cations such as 18 F-fluorobenzyl triphenylphosphonium cation 12 and [ 18 F]-CP18, 13 all of which target different processes in the apoptotic cascade. ...
Purpose
We investigated 2-(5-fluoro-pentyl)-2-methyl-malonic acid (¹⁸F-ML-10) positron emission tomography (PET) imaging of apoptosis posttherapy to determine optimal timing for predicting chemotherapy response in a mouse head/neck xenograft cancer model.
Procedures
BALB/c nude mice (4-8 weeks old) were implanted with UM-SCC-22B tumors. The treatment group received 2 doses of doxorubicin (10 mg/kg, days 0, 2). Small animal ¹⁸F-ML-10 PET/computed tomography was performed before and on days 1, 3, and 7 postchemotherapy. Using regions of interest around tumors, ¹⁸F-ML-10 uptake change was measured as %ID/g and uptake relative to liver. Terminal Uridine Nick-End Labeling (TUNEL) immunohistochemistry assay was performed using tumor samples of baseline and on days 1, 3, and 7 posttreatment.
Results
Treated mice demonstrated increased ¹⁸F-ML-10 uptake compared to baseline and controls, and 10 of 13 mice showed tumor volume decreases. All control mice showed tumor volume increases. Tumor-to-liver (T/L) ratios from the control group mice did not show significant change from baseline (P > .05); however, T/L ratios of the treatment group showed significant ¹⁸F-ML-10 uptake differences from baseline compared to days 3 and 7 posttreatment (P < .05), but no significant difference at 1 day posttreatment.
Conclusion
2-(5-Fluoro-pentyl)-2-methyl-malonic acid PET imaging has the potential for early assessment of treatment-induced apoptosis. Timing and image analysis strategies may require optimization, depending on the type of tumor and cancer treatment.
