PSA doubling time for prediction of [11C]choline PET/CT findings in prostate cancer patients with biochemical failure after radical prostatectomy

Purpose  

Previous studies have shown that the positive detection rate of [¹¹C]choline positron emission tomography/computed tomography (PET/CT) depends on prostate-specific antigen (PSA) plasma levels. This study compared PSA levels and PSA doubling time (PSADT) to predict [¹¹C]choline PET/CT findings.     

[11C]Choline PET/CT detection of bone metastases in patients with PSA progression after primary treatment for prostate cancer: comparison with bone scintigraphy

Purpose  

The aim of this study was to evaluate the clinical usefulness of [¹¹C]choline positron emission tomography (PET)/CT in comparison with bone scintigraphy (BS) in detecting bone metastases (BM) of patients with biochemical progression after radical treatment for prostate cancer (PCa).     

Prospective comparison of computed tomography,diffusion-weighted magnetic resonance imaging and [11C]choline positron emission tomography/computed tomography for preoperative lymph node staging in prostate cancer patients

Purpose

The aim of this study was to prospectively compare diffusion-weighted magnetic resonance imaging (DWI) and [¹¹C]choline positron emission tomography/computed tomography (PET/CT) with computed tomography (CT) for preoperative lymph node (LN) staging in prostate cancer (PCa) patients.

Methods

Between June 2010 and May 2012, CT, DWI and [¹¹C]choline PET/CT were performed preoperatively in 33 intermediate- and high-risk PCa patients undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND) including obturator fossa and internal, external and common iliac fields. Patient- and field-based performance characteristics for all three imaging techniques based on histopathological results are reported. Imaging techniques were compared by means of the area under the curve (AUC).

Results

LN metastases were detected in 92 of 1,012 (9 %) LNs from 14 of 33 (42 %) patients. On patient-based analysis, sensitivity, specificity and accuracy for CT were 57, 68 and 64 %, respectively, for DWI were 57, 79 and 70 %, respectively, and for [¹¹C]choline PET/CT were 57, 90 and 76 %, respectively. On field-based analysis, these numbers for CT were 47, 94 and 88 %, respectively, for DWI were 56, 97 and 92 %, respectively, and for [¹¹C]choline PET/CT were 62, 96 and 92 %, respectively. Neither DWI nor [¹¹C]choline PET/CT performed significantly better than CT on pairwise comparison of patient- and field-based results.

Conclusion

All three imaging techniques exhibit a rather low sensitivity with less than two thirds of LN metastases being detected on patient- and field-based analysis. Overall diagnostic efficacy did not differ significantly between imaging techniques, whereas distinct performance characteristics, esp. patient-based specificity, were best for [¹¹C]choline PET/CT followed by DWI and CT.     

Synthesis and evaluation of a new vesamicol analog <Emphasis Type="Italic">o</Emphasis>-[<Superscript>11</Superscript>C]methyl-<Emphasis Type="Italic">trans</Emphasis>-decalinvesamicol as a PET ligand for the vesicular acetylcholine transporter

Introduction

We focused on the vesicle acetyl choline transporter (VAChT) as target for early diagnosis of Alzheimer’s diseases because the dysfunction of the cholinergic nervous system is closely associated with the symptoms of AD, such as problem in recognition, memory, and learning. Due to its low binding affinity for the sigma receptors (σ-1 and σ-2), o-methyl-trans-decalinvesamicol (OMDV) demonstrated a high binding affinity and selectivity for vesicular acetyl choline transporter (VAChT). [¹¹C]OMDV was prepared and investigated the potential as a new PET ligand for VAChT imaging through in vivo evaluation.

Method

[¹¹C]OMDV was prepared by a palladium-promoted cross-coupling reaction using [¹¹C]methyl iodide, with a radiochemical yield of 60–75 %, a radiochemical purity of greater than 98 %, and a specific activity of 5–10 TBq/mmol 30 min after EOB. In vivo biodistribution study of [¹¹C]OMDV in blood, brain regions and major organs of rats was performed at 2, 10, 30 and 60 min post-injection. In vivo blocking study and PET–CT imaging study were performed to check the binding selectivity of [¹¹C]OMDV for VAChT.

Results

In vivo studies demonstrated [¹¹C]OMDV passage through the blood–brain barrier (BBB) and accumulation in the rat brain. The regional brain accumulation of [¹¹C]OMDV was significantly inhibited by co-administration of vesamicol. In contrast, brain accumulation of [¹¹C]OMDV was not significantly altered by co-administration of (+)-pentazocine, a selective σ-1 receptor ligand, or (+)-3-(3-hydroxyphenyl)-N-propylpiperidine [(+)-3-PPP], a σ-1 and σ-2 receptor ligand. PET–CT imaging revealed inhibition of [¹¹C]OMDV accumulation in the brain by co-administration of vesamicol.

Conclusion

[¹¹C]OMDV selectively binds to VAChT with high affinity in the rat brain in vivo, and that [¹¹C]OMDV may be utilized in the future as a specific VAChT ligand for PET imaging.

     

[11C]Choline as pharmacodynamic marker for therapy response assessment in a prostate cancer xenograft model

Purpose

[¹¹C]Choline has been established as a PET tracer for imaging prostate cancer. The aim of this study was to determine whether [¹¹C]choline can be used for monitoring the effects of therapy in a prostate cancer mouse xenograft model.

Methods

The androgen-independent human prostate cancer cell line PC-3 was implanted subcutaneously into the flanks of 13 NMRI (nu/nu) mice. All mice were injected 4–6 weeks after xenograft implantation with 37 MBq [¹¹C]choline via a tail vein. Dynamic imaging was performed for 60 min with a small-animal PET/CT scanner (Siemens Medical Solutions). Six mice were subsequently injected intravenously with docetaxel twice (days 1 and 5) at a dose of 3 mg/kg body weight. Seven mice were treated with PBS as a control. [¹¹C]Choline imaging was performed prior to and 1, 2 and 3 weeks after treatment. To determine choline uptake the images were analysed in terms of tumour-to-muscle (T/M) ratios. Every week the size of the implanted tumour was determined with a sliding calliper.

Results

The PC-3 tumours could be visualized by [¹¹C]choline PET. Before treatment the T/M_mean ratio was 1.6±0.5 in the control group and 1.8±0.4 in the docetaxel-treated group (p=0.65). There was a reduction in the mean [¹¹C]choline uptake after docetaxel treatment as early as 1 week after initiation of therapy (T/M ratio 1.8±0.4 before treatment, 0.9±0.3 after 1 week, 1.1±0.3 after 2 weeks and 0.8±0.2 after 3 weeks). There were no decrease in [¹¹C]choline uptake in the control group following treatment (T/M ratio 1.6±0.5 before treatment, 1.7±0.4 after 1 week, 1.8±0.7 after 2 weeks and 1.7±0.4 after 3 weeks). For analysis of the dynamic data, a generalized estimation equation model revealed a significant decrease in the T/M_dyn ratios 1 week after docetaxel treatment, and the ratio remained at that level through week 3 (mean change ?0.93±0.24, p<0.001, after 1  week; ?0.78±0.21, p<0.001, after 2 weeks; ?1.08±0.26, p<0.001, after 3 weeks). In the control group there was no significant decrease in the T/M_dyn ratios (mean change 0.085±0.39, p=0.83, after 1 week; 0.31±0.48, p=0.52, after 2 weeks; 0.11±0.30, p=0.72, after 3 weeks). Metabolic changes occurred 1 week after therapy and preceded morphological changes of tumour size during therapy.

Conclusion

Our results demonstrate that [¹¹C]choline has the potential for use in the early monitoring of the therapeutic effect of docetaxel in a prostate cancer xenograft animal model. The results also indicate that PET with radioactively labelled choline derivatives might be a useful tool for monitoring responses to taxane-based chemotherapy in patients with advanced prostate cancer.     

Predictive factors of [11C]choline PET/CT in patients with biochemical failure after radical prostatectomy

Purpose

Detection of recurrence in prostate cancer patients with biochemical failure after radical prostatectomy by [¹¹C]choline PET/CT depends on the prostate-specific antigen (PSA) level. The role of other clinical and pathological variables has not been explored.

Methods

A total of 2,124 prostate cancer patients referred to our Institution for [¹¹C]choline PET/CT from December 2004 to January 2007 for restaging of disease were retrospectively considered for this study. Inclusion criteria were: previous treatment by radical prostatectomy, and biochemical failure, defined as at least two consecutive PSA measurements of >0.2 ng/ml. These criteria were met for 358 patients. Binary logistic analysis was used to investigate the predictive factors of [¹¹C]choline PET/CT. PET/CT findings were validated using criteria based on histological analysis, and follow-up clinical and imaging data. Receiver operating characteristic (ROC) analysis was used to assess the performance of [¹¹C]choline PET/CT in relation to PSA levels.

Results

The mean PSA level was 3.77?±?6.94 ng/ml (range 0.23–45 ng/ml; median 1.27 ng/ml). PET/CT was positive for recurrence in 161 of 358 patients (45%). On an anatomical region basis, [¹¹C]choline pathological uptake was observed in lymph nodes (107/161 patients, 66%), prostatectomy bed (55/161 patients, 34%), and in the skeleton (46/161 patients, 29%). PET/CT findings were validated using histological criteria (46/358, 13%), and follow-up clinical and imaging criteria (312/358, 87%). Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were, respectively, 85%, 93%, 91%, 87%, and 89%. In multivariate analysis, high PSA levels, advanced pathological stage, previous biochemical failure and older age were significantly (P?<?0.05) associated with an increased risk of positive PET/CT findings. The percentage of positive scans was 19% in those with a PSA level between 0.2 and 1 ng/ml, 46% in those with a PSA level between 1 and 3 ng/ml, and 82% in those with a PSA level higher than 3 ng/ml. ROC analysis showed that PET/CT-positive and PET/CT-negative patients could be best distinguished using a PSA cut-off value of 1.4 ng/ml.

Conclusions

In addition to PSA levels, pathological stage, previous biochemical failure and age should be considered by physicians when referring prostate cancer patients with biochemical failure after radical prostatectomy to [¹¹C]choline PET/CT.     

Comparison of integrated whole-body [11C]choline PET/MR with PET/CT in patients with prostate cancer

Purpose

To evaluate the performance of conventional [¹¹C]choline PET/CT in comparison to that of simultaneous whole-body PET/MR.

Methods

The study population comprised 32 patients with prostate cancer who underwent a single-injection dual-imaging protocol with PET/CT and subsequent PET/MR. PET/CT scans were performed applying standard clinical protocols (5 min after injection of 793?±?69 MBq [¹¹C]choline, 3 min per bed position, intravenous contrast agent). Subsequently (52?±?15 min after injection) PET/MR was performed (4 min per bed position). PET images were reconstructed iteratively (OSEM 3D), scatter and attenuation correction of emission data and regional allocation of [¹¹C]choline foci were performed using CT data for PET/CT and segmented Dixon MR, T1 and T2 sequences for PET/MR. Image quality of the respective PET scans and PET alignment with the respective morphological imaging modality were compared using a four point scale (0–3). Furthermore, number, location and conspicuity of the detected lesions were evaluated. SUVs for suspicious lesions, lung, liver, spleen, vertebral bone and muscle were compared.

Results

Overall 80 lesions were scored visually in 29 of the 32 patients. There was no significant difference between the two PET scans concerning number or conspicuity of the detected lesions (p not significant). PET/MR with T1 and T2 sequences performed better than PET/CT in anatomical allocation of lesions (2.87?±?0.3 vs. 2.72?±?0.5; p?=?0.005). The quality of PET/CT images (2.97?±?0.2) was better than that of the respective PET scan of the PET/MR (2.69?±?0.5; p?=?0.007). Overall the maximum and mean lesional SUVs exhibited high correlations between PET/CT and PET/MR (ρ?=?0.87 and ρ?=?0.86, respectively; both p?<?0.001).

Conclusion

Despite a substantially later imaging time-point, the performance of simultaneous PET/MR was comparable to that of PET/CT in detecting lesions with increased [¹¹C]choline uptake in patients with prostate cancer. Anatomical allocation of lesions was better with simultaneous PET/MR than with PET/CT, especially in the bone and pelvis. These promising findings suggest that [¹¹C]choline PET/MR might have a diagnostic benefit compared to PET/CT in patients with prostate cancer, and now needs to be further evaluated in prospective trials.     

PET imaging of hepatocellular carcinoma with <Superscript>18</Superscript>F-fluoroethylcholine and <Superscript>11</Superscript>C-choline

Purpose  

Choline-based radiotracers have been studied for PET imaging of hepatocellular carcinoma (HCC). Using an ¹⁸F-labeled choline analog, instead of the ¹¹C-labeled native choline, would facilitate its widespread use in the clinic. In this study, PET with ¹⁸F-fluoroethylcholine (FEC) and ¹¹C-choline (CHOL) were compared using an animal model of HCC. The effects of fasting on the performance of choline-based tracers were also investigated.     

Biodistribution and radiation dosimetry of 11C-labelled docetaxel in cancer patients

Purpose  

Docetaxel is an important chemotherapeutic agent used for the treatment of several cancer types. As radiolabelled anticancer agents provide a potential means for personalized treatment planning, docetaxel was labelled with the positron emitter ¹¹C. Non-invasive measurements of [¹¹C]docetaxel uptake in organs and tumours may provide additional information on pharmacokinetics and pharmacodynamics of the drug docetaxel. The purpose of the present study was to determine the biodistribution and radiation absorbed dose of [¹¹C]docetaxel in humans.     

Reproducibility of automated simplified voxel-based analysis of PET amyloid ligand [<Superscript>11</Superscript>C]PIB uptake using 30-min scanning data

Purpose  

Positron emission tomography (PET) with ¹¹C-labelled Pittsburgh compound B ([¹¹C]PIB) enables the quantitation of β-amyloid accumulation in the brain of patients with Alzheimer’s disease (AD). Voxel-based image analysis techniques conducted in a standard brain space provide an objective, rapid and fully automated method to analyze [¹¹C]PIB PET data. The purpose of this study was to evaluate both region- and voxel-level reproducibility of automated and simplified [¹¹C]PIB quantitation when using only 30 min of imaging data.     

First automatic radiosynthesis of <Superscript>11</Superscript>C labeled Telmisartan using a multipurpose synthesizer for clinical research use

Objective  

Telmisartan, a nonpeptide angiotensin II AT1 receptor antagonist, is an antihypertensive drug. Positron emission tomography (PET) imaging with [¹¹C]Telmisartan is expected to provide information about the whole body pharmacokinetics of telmisartan as well as the transport function of hepatic OATP1B3. We developed a first automatic preparation system of [¹¹C]Telmisartan to applicable clinical research using a new ¹¹C and ¹⁸F multipurpose synthesizer.     

Potential of [<Superscript>11</Superscript>C]acetate for measuring myocardial blood flow: Studies in normal subjects and patients with hypertrophic cardiomyopathy

Background  

Measuring the rate of clearance of carbon-11 labelled acetate from myocardium using positron emission tomography (PET) is an accepted technique for noninvasively assessing myocardial oxygen consumption. Initial myocardial uptake of [¹¹C]acetate, however, is related to myocardial blood flow (MBF) and several tracer kinetic models for quantifying MBF using [¹¹C]acetate have been proposed. The objective of this study was to assess these models.     

Prospective evaluation of [<Superscript>11</Superscript>C]Choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer

Purpose

The aim of this study was to prospectively evaluate the value of [¹¹C] Choline PET/CT in monitoring early and late response to a standardized first-line docetaxel chemotherapy in castration refractory prostate cancer (mCRPC) patients.

Methods

Thirty-two patients were referred for [¹¹C] Choline PET/CT before the start of docetaxel chemotherapy, after one and ten chemotherapy cycles (or - in case of discontinuation - after the last administered cycle) for therapy response assessment. [¹¹C] Choline uptake (SUV_max, SUV_mean), CT derived Houndsfield units (HU_max, HU_mean), and volume of bone, lung, and nodal metastases and local recurrence were measured semi-automatically at these timepoints. Change in SUV_max, SUV_mean, HU_max, HU_mean, and volume was assessed between PET 2 and 1 (early response assessment, ERA) and PET 3 and 1 (late response assessment, LRA) on a patient and lesion basis. Results of PET/CT were compared to clinically used RECIST 1.1 and clinical criteria based therapy response assessment including PSA for defining progressive disease (PD) and non-progressive disease (nPD), respectively. Relationships between changes of SUV_max and SUV_mean (early and late) and changes of PSA_early and PSA_late were evaluated. Prognostic value of initial SUV_max and SUV_mean was assessed. Statistical analyses were performed using SPSS.

Results

In the patient-based ERA and LRA there were no statistically significant differences in change of choline uptake, HU, and volume between PD and nPD applying RECIST or clinical response criteria. In the lesion-based ERA, decrease in choline uptake of bone metastases was even higher in PD (applying RECIST criteria), whereas in LRA the decrease was higher in nPD (applying clinical criteria). There were only significant correlations between change in choline uptake and PSA in ERA in PD, in LRA no significant correlations were discovered. Initial SUV_max and SUV_mean were statistically significantly higher in nPD (applying clinical criteria).

Conclusion

There is no significant correlation between change in choline uptake in [¹¹C] Choline PET/CT and clinically routinely used objective response assessment during the early and late course of docetaxel chemotherapy. Therefore, [¹¹C] Choline PET/CT seems to be of limited use in therapy response assessment in standardized first-line chemotherapy in mCRPC patients.

     

Daunorubicin and doxorubicin inhibit the [C]choline accumulation in cancer cells

We studied how very short (10–40 min) incubation with anthracycline derivatives modifies the accumulation of PET tumor-diagnostic radiotracers in cancer cells. The human ovarian A2780 and A2780AD, human B lymphoid JY, human epidermoid KB-3-1 and KB-V-1, and smooth muscle DDT1 MF-2 cells were pre-incubated with daunorubicin and doxorubicin, and the uptake of [¹⁸F]FDG and [¹¹C]choline was measured. Anthracycline treatment decreased remarkably the [¹¹C]choline accumulation in a concentration dependent manner, while it did not modify significantly the [¹⁸F]FDG uptake of the cells.     

Tumour volume delineation in prostate cancer assessed by [11C]choline PET/CT: validation with surgical specimens

Purpose

PET has been proven to be helpful in the delineation of gross tumour volume (GTV) for external radiation therapy in several tumour entities. The aim of this study was to determine if [¹¹C]choline PET could be used to localize the carcinomatous tissue within the prostate in order to specifically target this area for example with high-precision radiation therapy.

Methods

Included in this prospective study were 20 patients with histological proven prostate carcinoma who underwent [¹¹C]choline PET/CT before radical prostatectomy. After surgical resection, specimens were fixed and cut into 5-mm step sections. In each section the area of the carcinoma was delineated manually by an experienced pathologist and digitalized, and the histopathological tumour volume was calculated. Shrinkage due to resection and fixation was corrected using in-vivo and ex-vivo CT data of the prostate. Histopathological tumour location and size were compared with the choline PET data. Different segmentation algorithms were applied to the PET data to segment the intraprostatic lesion volume.

Results

A total of 28 carcinomatous lesions were identified on histopathology. Only 13 (46 %) of these lesions had corresponding focal choline uptake. In the remaining lesions, no PET uptake (2 lesions) or diffuse uptake not corresponding to the area of the carcinoma (13 lesions) was found. In the patients with corresponding PET lesions, no suitable SUV threshold (neither absolute nor relative) was found for GTV segmentation to fit the volume to the histological tumour volume.

Conclusion

The choline uptake pattern corresponded to the histological localization of prostate cancer in fewer than 50 % of lesions. Even when corresponding visual choline uptake was found, this uptake was highly variable between patients. Therefore SUV thresholding with standard algorithms did not lead to satisfying results with respect to defining tumour tissue in the prostate.     

In vivo positron emission tomography imaging with [<Superscript>11</Superscript>C]ABP688: binding variability and specificity for the metabotropic glutamate receptor subtype 5 in baboons

Purpose  

Metabotropic glutamate receptor subtype 5 (mGluR5) dysfunction has been implicated in several disorders. [¹¹C]ABP688, a positron emission tomography (PET) ligand targeting mGluR5, could be a valuable tool in the development of novel therapeutics for these disorders by establishing in vivo drug occupancy. Due to safety concerns in humans, these studies may be performed in nonhuman primates. Therefore, in vivo characterization of [¹¹C]ABP688 in nonhuman primates is essential.     

Two activated stages of microglia and PET imaging of peripheral benzodiazepine receptors with [<Superscript>11</Superscript>C]PK11195 in rats

Objective  

The transition of microglia from the normal resting state to the activated state is associated with an increased expression of peripheral benzodiazepine receptors (PBR). The extent of PBR expression is dependent on the level of microglial activation. A PBR ligand, [¹¹C]PK11195, has been used for imaging of the activation of microglia in vivo. We evaluated whether [¹¹C]PK11195 PET can indicate differences of microglial activation between no treatment and lipopolysaccharide (LPS) treatment in a rat artificial injury model of brain inflammation.     

PET imaging of focal demyelination and remyelination in a rat model of multiple sclerosis: comparison of [11C]MeDAS, [11C]CIC and [11C]PIB

Purpose

In this study, we compared the ability of [¹¹C]CIC, [¹¹C]MeDAS and [¹¹C]PIB to reveal temporal changes in myelin content in focal lesions in the lysolecithin rat model of multiple sclerosis. Pharmacokinetic modelling was performed to determine the best method to quantify tracer uptake.

Methods

Sprague-Dawley rats were stereotactically injected with either 1 % lysolecithin or saline into the corpus callosum and striatum of the right brain hemisphere. Dynamic PET imaging with simultaneous arterial blood sampling was performed 7 days after saline injection (control group), 7 days after lysolecithin injection (demyelination group) and 4 weeks after lysolecithin injection (remyelination group).

Results

The kinetics of [¹¹C]CIC, [¹¹C]MeDAS and [¹¹C]PIB was best fitted by Logan graphical analysis, suggesting that tracer binding is reversible. Compartment modelling revealed that all tracers were fitted best with the reversible two-tissue compartment model. Tracer uptake and distribution volume in lesions were in agreement with myelin status. However, the slow kinetics and homogeneous brain uptake of [¹¹C]CIC make this tracer less suitable for in vivo PET imaging. [¹¹C]PIB showed good uptake in the white matter in the cerebrum, but [¹¹C]PIB uptake in the cerebellum was low, despite high myelin density in this region. [¹¹C]MeDAS distribution correlated well with myelin density in different brain regions.

Conclusion

This study showed that PET imaging of demyelination and remyelination processes in focal lesions is feasible. Our comparison of three myelin tracers showed that [¹¹C]MeDAS has more favourable properties for quantitative PET imaging of demyelinated and remyelinated lesions throughout the CNS than [¹¹C]CIC and [¹¹C]PIB.     

No inhibitory effect on P-glycoprotein function at blood–brain barrier by clinical dose of clarithromycin: a human PET study with [<Superscript>11</Superscript>C]verapamil

Objective  

To investigate the effects of the clinical dose of clarithromycin, a substrate of P-glycoprotein (P-gp), on P-gp function using positron emission tomography (PET) with [¹¹C]verapamil.     

Synthesis and evaluation of [11C]XR9576 to assess the function of drug efflux transporters using PET

Objective

XR9576 (tariquidar) is an anthranilic acid derivative and potent P-glycoprotein (P-gp) inhibitor. XR9576 has undergone phase I and II studies as combined chemotherapy against cancer. XR9576 has been developed as a useful therapeutic agent but not as a PET probe. We therefore developed [¹¹C]XR9576 as a PET probe and assessed whether PET studies using [¹¹C]XR9576 are a promising approach to assess P-gp function primarily.

Methods

We synthesized [¹¹C]XR9576 by methylation of 7-O-desmethyl XR9576 with [¹¹C]methyl iodide. In in vivo tissue distribution, the effects of co-injection with XR9576 on the uptake of [¹¹C]XR9576 in mice were investigated. PET studies using [¹¹C]XR9576 were performed in P-gp and/or Bcrp knockout mice as well as in wild-type mice. Metabolites of [¹¹C]XR9576 were measured in the brain and plasma of mice.

Results

[¹¹C]XR9576 was successfully synthesized with suitable radioactivity for injection as well as appropriate radiochemical purity and stability. In in vivo tissue distribution, the brain uptake of [¹¹C]XR9576 significantly increased about tenfold of control on co-injection with >10 mg/kg of XR9576. In PET studies, the AUC_{brain [0–60 min]} in P-gp and P-gp/Bcrp knockout mice was 2- and 11-fold higher than that in wild-type mice. [¹¹C]XR9576 showed a high metabolic stability (>90% unchanged form) in the brain and plasma of mice 30 min after injection. These results suggest that a tracer amount of [¹¹C]XR9576 behave as the P-gp and Bcrp substrate, and the increased brain uptake or AUC_brain of [¹¹C]XR9576 correlates with P-gp and Bcrp functions.

Conclusions

PET studies using [¹¹C]XR9576 may be a promising approach for evaluating deficiency of the function of drug efflux transporters targeting intracranial diseases and tumors.