PET Tracer Uptake Research Articles

6Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage

6Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage

6 Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage

6 Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage

Whole-body PET/CT imaging: Combining software- and hardware-based co-registration

Aim Combined whole-body (WB) PET/CT imaging provides better overall co-registration compared to separate CT and PET. However, in clinical routine local PET-CT mis-registration cannot be avoided. Thus, the reconstructed PET tracer distribution may be biased when using the misaligned CT transmission data for CT-based attenuation correction (CT-AC). We investigate the feasibility of retrospective co-registration techniques to align CT and PET images prior to CT-AC, thus improving potentially the quality of combined PET/CT imaging in clinical routine. Methods First, using a commercial software registration package CT images were aligned to the uncorrected PET data by rigid and non-rigid registration methods. Co-registration accuracy of both alignment approaches was assessed by reviewing the PET tracer uptake patterns (visual, linked cursor display) following attenuation correction based on the original and co-registered CT. Second, we investigated non-rigid registration based on a prototype ITK implementation of the B-spline algorithm on a similar targeted MR-CT registration task, there showing promising results. Results Manual rigid, landmark-based co-registration introduced unacceptable misalignment, in particular in peripheral areas of the whole-body images. Manual, non-rigid landmark-based co-registration prior to CT-AC was successful with minor loco-regional distortions. Nevertheless, neither rigid nor non-rigid automatic co-registration based on the Mutual Information image to image metric succeeded in co-registering the CT and noAC-PET images. In contrast to widely available commercial software registration our implementation of an alternative automated, non-rigid B-spline co-registration technique yielded promising results in this setting with MR-CT data. Conclusion In clinical PET/CT imaging, retrospective registration of CT and uncorrected PET images may improve the quality of the AC-PET images. As of today no validated and clinically viable commercial registration software is in routine use. This has triggered our efforts in pursuing new approaches to a validated, non-rigid co-registration algorithm applicable to whole-body PET/CT imaging of which first results are presented here. This approach appears suitable for applications in retrospective WB-PET/CT alignment.

Further characterization of the epidermal growth factor receptor ligand 11C-PD153035

(11)C-4-N-(3-bromoanilino)-6,7-dimethoxyquinazoline ((11)C-PD153035) has been reported as a tracer for imaging human tumors that overexpress epidermal growth factor receptor (EGFR). However it is still unclear whether (11)C-PD153035 uptake correlates with EGFR expression levels. The objective of this study was to investigate the relationship between (11)C-PD153035 accumulation and EGFR expression levels. Synthesis of (11)C-PD153035 was performed in the Tracerlab FXc system. Accumulation of (11)C-PD153035 by MDA-MB-468, A549 and MDA-MB-231 cells was measured in vitro. There were six tumor-bearing mice in each group. (11)C-PD153035 uptake in tumors was determined by positron emission tomography/computed tomography (PET/CT). Tumor/normal muscle tissue (T/NT) analysis in PET images was applied to quantify the PET data. Sixty minutes after PET/CT scanning, the nude mice were sacrificed and the tumors were excised. The (11)C-PD153035 accumulation in different tumors was determined by a gamma counter. Close correlation existed between the uptake and the level of EGFR expression both in vitro and ex vivo (r(2) = 0.72, P < 0.001; r(2) = 0.63, P = 0.003). When the static T/NT analysis method was applied to analyze the PET data, the observed correlation was again excellent (r(2) = 0.70, P = 0.001). The uptake of PET tracer (11)C-PD153035 closely correlates with the EGFR expression levels in tumor cells. (11)C-PD153035 has the potential to yield useful information for both cancer diagnosis and therapy.

SU‐FF‐J‐89: Intratumoral Pattern of FDG Uptake in Human Xenograft Models

Purpose: To investigate the spatial association between intratumoral uptake of 18F‐fluorodeoxyglucose (18F‐FDG) and the following characteristics of the tumor microenvironment: hypoxia, cellular proliferation, and blood flow; and to evaluate the potential impact of this association on the use of 18F‐FDG images in radiation oncology treatment planning for target volume delineation. Method and Materials: Six nude rats were inoculated with the following human tumor cells: HT‐29 (colon adenocarcinoma), DU‐145 (prostate carcinoma), and A549 (NSCLC). When the tumors reached 20–25mm in diameter, the animals were injected with 18F‐FDG, pimonidazole, and bromodeoxyuridine. 1hr post injection animals were imaged on animal PET scanner. Upon completion of imaging, animals were injected with Hoechst33342 and sacrificed with CO2 5–10min later. Tumors were immediately dissected, frozen and cut into 8μm thick sections. One section from each tumor was placed onto a phosphor plate for autoradiography. The images of the fluorescence produced by Hoechst33342 and by fluorescent antibodies raised against pimonidazole and bromodeoxyuridine were acquired from the adjacent sections and co‐registered. The statistical analysis of association between PET tracer uptake and microenvironmental markers was then performed on a pixel‐by‐pixel basis. Results: In all the tumor models studied, we observed positive pixel‐by‐pixel correlation between FDG uptake and pimonidazole staining intensity (correlation coefficients ranged from 0.46 to 0.87, p&lt;0.001). At the same time, correlation with bromodeoxyuridine was always negative (ranged from −0.50 to −0.78, p&lt;0.001). Conclusions: This study further confirms association between foci of increased intratumoral FDG uptake and regions of hypoxia. In addition, it demonstrates reduced FDG uptake in actively growing parts of the tumor. Therefore, the use of FDG uptake iso‐contours to delineate lesions and, especially, to reduce target volume with respect to CT‐defined volume should be approached very carefully, since it might potentially result in exclusion of areas of active tumor growth from the target volume.

Episodic receptive aphasia in a child with Landau–Kleffner Syndrome: PET correlates

We report a four-year-old boy with Landau–Kleffner Syndrome (LKS) characterized by episodic receptive aphasia lasting for few weeks followed by gradual recovery of baseline language functions. Neuropsychological evaluation during an episode showed severe impairment in verbal skills and comprehension, but relative preservation of non-verbal skills. Although he could carry on a conversation during remission, neuropsychological evaluation demonstrated findings reflective of receptive language deficits. Prolonged EEG disclosed frequent sharp-wave activity in the left and right temporal regions but no electrographic seizures. Glucose metabolism PET scan during the fourth episode of aphasia revealed intense hypermetabolism in the left temporal neocortex. Awake EEG during the PET tracer uptake period showed 6.0 spikes/min in the left temporal region and 4.0 spikes/min in the right. A repeat PET scan during remission showed hypometabolism in the left temporal cortex. Awake EEG during the FDG uptake period showed 16.0 spikes/min in the right temporal region and 0.3 spikes/min in the left. During his fifth aphasic episode, EEG (without PET) showed 0.16 spikes/min in the right temporal region and none in the left. Intermittent short episodes of predominantly receptive aphasia with near-total recovery between episodes can be one of the clinical presentations of LKS. This case illustrates the dynamic changes of glucose metabolism in the temporal lobe during episodes of aphasia and remission in a case with LKS. The clinical course of our patient with transient EEG and PET findings suggest that glucose metabolism in LKS cannot be attributed solely to interictal epileptiform activities on scalp EEG.

MO-D-I-609-08: Validation of PET Hypoxia Tracers by Autoradiography and Fluorescent Microscopy

Purpose: To develop a method for PET hypoxia tracer validation based on statistical analysis of the spatial correspondence between the intratumoral distributions of tracer uptake (assessed by digital autoradiography) and pimonidazole, an independent marker of hypoxia (assessed by immunofluorescent microscopy). The utility of the method was demonstrated by applying it to three PET hypoxia tracers, IAZGP, FMISO and Cu-ATSM. Method and Materials: Eight rats bearing R3327-AT tumors were divided into four groups of two animals each. Group♯1 was injected with 18F-FMISO and sacrificed 2hr later. Group♯2 was injected with 124I-IAZGP and sacrificed 3hr later. Groups♯3 and ♯4 were injected with 64Cu-ATSM and sacrificed, respectively, 24hr or 1hr later. Pimonidazole was administered to all animals 2hr before sacrifice. Tumors were excised, frozen and sectioned. Digital autoradiograms of the tracer distribution were obtained from selected sections and co-registered with images of pimonidazole-associated immunofluorescence derived from adjacent sections. The statistical analysis of association between PET tracer uptake and pimonidazole immunofluorescent staining intensity was then performed on a pixel-by-pixel basis. Results: For rats from group♯1 correlation coefficients between pimonidazole-associated immunofluorescent staining intensity and 18F-FMISO uptake were 0.84 and 0.75. For group♯2 rats correlations between pimonidazole and 124I-IAZGP were 0.85 and 0.77. For group♯3 (64Cu-ATSM administered 24hr prior to sacrifice), the correlations with pimonidazole were 0.61 and 0.64. However, for group♯4 (64Cu-ATSM administered 1hr prior to sacrifice), the correlation coefficients were −0.76 and −0.77, demonstrating that in this tumor model 64Cu-ATSM uptake was not indicative of hypoxia at early times post injection. Conclusion: The proposed method enables evaluation of the degree of spatial correspondence between distributions of a PET tracer and alternative markers (either endogenous or exogenous) or tracers of the biological process under study. This method can be used for the in-vivo validation of any nuclear medicine tracer.

Effects of 2-methoxyestradiol on proliferation, apoptosis and PET-tracer uptake in human prostate cancer cell aggregates

The purpose of this study was to investigate the potential use of PET in vivo to record cytotoxic effects of 2-methoxyestradiol (2-ME), an endogenous metabolite of 17β-estradiol. The anti-proliferative and pro-apoptotic effects of 2-ME on human prostate cancer cell (PC3) aggregates in vitro, were correlated with the uptake of fluoro-deoxy-D-glucose, FMAU and choline labelled with 18F, 11C, or 3H. 2-ME clearly reduced growth of PC3 aggregates and induced apoptosis in a dose-dependent manner. However, the uptake of the putative proliferation markers 11C-FMAU or 3H-choline failed to record the growth inhibitory effects of 2-ME on PC3 cell aggregates. The uptake of 18F-FDG was used as a marker for effects on cellular metabolism and also failed to show any dose-dependent effects in PC3 aggregates. The use of these PET-tracers in vivo is therefore not recommended in order to evaluate the cytotoxic effects of 2-ME on human prostate cancer cells.