Carbon nanotubes as gene carriers: Focus on internalization pathways related to functionalization and properties.

Carbon nanotubes represent promising transporters for delivery of DNA and other biomolecules into living cells. Various methods of CNTs surface functionalization have been developed. These are essential to improve CNTs dispersibility and permit their interactions with biological structures that broaden their use in advanced biomedical applications. The present review discusses the different single walled carbon nanotubes and multiwalled carbon nanotubes functionalization methods, leading to the formation of optimized and functionalized-CNT complexes with DNA. F-CNTs are recognized as efficient and promising gene carriers. Emphasis is then placed on the processes used by f-CNTs/DNA complexes to cross cell membranes. Energy independent pathways and uptake mechanisms dependent on energy, such as endocytosis or phagocytosis, are reported by many studies, and if these mechanisms seem contradictory at first sight, a detailed review of the literature illustrates that they are rather complementary. Preferential use of one or the other depends on the DNA and CNTs chemical nature and physical parameters, experimental procedures and cell types. STATEMENT OF SIGNIFICANCE: Efficient non-viral gene delivery is desirable, yet challenging. CNTs appear as a promising solution to penetrate into cells and successfully deliver DNA. Moreover, the field of use of CNTs as gene carrier is large and is currently growing. This critical review summarizes the development and evaluation of CNTs as intracellular gene delivery system and provides an overview of functionalized CNTs/DNA cellular uptake mechanisms, depending on several parameters of CNTs/DNA complexes.

Nanovectorization of DNA Through Cells Using Protamine Complexation.

Carbon nanotubes (CNT) are currently used as a promising family of nanovectors able to deliver different types of therapeutic molecules. Several applications dealing with CNT used as drug nanocarriers have been developed since their ability to penetrate into the cells has been proved. CNT can thus load several active molecules to various cells. In this paper, we will use molecular dynamic simulation to describe theoretically the potential of CNT to transport and deliver DNA through the formation of protamine-DNA-CNT complex.

Study of inter- and intra-observer reproducibility in the interpretation of [(18)F]choline PET/CT examinations in patients suffering from biochemically recurrent prostate cancer following curative treatment.

BACKGROUND: The aim of this study was to investigate the reproducibility of intra- and inter-observer interpretation of [(18)F]choline positron emission tomography/computed tomography examinations in patients suffering from biochemically recurrent prostate cancer following curative treatment. METHODS: A total of 60 patients with biochemical recurrence after curative treatment were included in this bicentric study. The interpretations were based on a systematic analysis of several anatomic regions and all the four nuclear medicine physicians used identical result consoles. The examinations were interpreted with no knowledge of the patients' clinical context. Two months later, a second interpretation of all these examinations was performed using the same method, in random order. RESULTS: To evaluate local recurrences, when the prostate is in place, the results showed moderate inter- and intra-observer reproducibility: concordance of all 4 physicians has a Fleiss' kappa coefficient of 0.553 with a confidence interval of (0.425 to 0.693). For patients who had had a prostatectomy, there was excellent concordance for the negative examinations. For the lymphatic basin, inter- and intra-observer reproducibility was excellent with a Fleiss' kappa coefficient of 0.892 with a confidence interval of (0.788 to 0.975). The lymphatic sub-group analysis was also good. For the lymphatic groups in the right or left hemi-pelves, all Fleiss' kappa and Cohen's kappa coefficients are varying from 0.760 to 1 with narrow confidence intervals from (0.536 to 0.984) to (1 to 1) in favour of good/excellent inter-observer reproducibility. To evaluate bone metastasis, inter-observer reproducibility was good with a Fleiss' kappa coefficient of 0.703 and a confidence interval of (0.407 to 0.881). CONCLUSION: Our study is at time the only one on the reproducibility of interpretation of [(18)F]choline positron emission tomography/computed tomography examinations, which is a key examination for the treatment of patients suffering biochemical recurrence of prostate cancer. Interpretation of the [(18)F]choline positron emission tomography/computed tomography examination is not so useful at prostate level in patients not previously treated with prostatectomy but has a great interest on patients treated by prostatectomy. It showed good concordance in the interpretation of sub-diaphragmatic lymphatic recurrences as well as in bone metastasis.

Granulosa cell tumor of the ovary with high FDG uptake.

Granulosa cell tumor (GCT) of the ovary is a rare tumor accounting for 2%-5% of ovarian malignancies. Although the usefulness of 18F-FDG PET/CT is well demonstrated in the staging and follow-up of the great majority of ovarian cancers, GCTs are known to cause false-negative results on FDG PET because of very low FDG avidity. We present a case of a GCT in which an 18F-FDG PET/CT proved very useful in the detection of recurrence.

18F-fluoride PET/CT aspect of an unusual case of Erdheim-Chester disease with histologic features of Langerhans cell histiocytosis.

We report the case of a 63-year-old woman with Erdheim-Chester disease (ECD) and histologic features of Langerhans cell histiocytosis, both extremely rare histiocytic proliferations responsible of skeletal and extraskeletal involvement. 18F-Fluoride PET/CT revealed multiple intense focal uptake scattered throughout the skeleton. We also performed an 18F-FDG PET/CT which point out visceral and vascular involvement. This case illustrates the interest of PET/CT in ECD, a rare polymorphus and systemic disease, and in our knowledge, this is the first reported illustration of 18F-fluoride PET/CT findings in this pathology.

The role of delayed 18F-FDG PET imaging in the follow-up of patients with alveolar echinococcosis.

UNLABELLED: (18)F-FDG PET has already proved its usefulness in the follow-up of patients with alveolar echinococcosis (AE) and has been proposed as a surrogate marker for therapeutic decisions on structured treatment interruption by benzimidazoles. However, standard PET acquisition (1 h after (18)F-FDG injection) lacks sensitivity, and the parasite may stay viable even if (18)F-FDG perilesional uptake has disappeared. The aim of our study was to evaluate the usefulness of delayed (18)F-FDG PET in the management of AE patients. METHODS: During a 6-y period, 120 PET scans using (18)F-FDG were obtained for 70 AE patients treated by benzimidazoles, without selection. All patients underwent whole-body imaging on a PET/CT device 1 h after (18)F-FDG injection (4 MBq/kg), as well as an acquisition focused on the liver 3 h after the injection. We also analyzed the results of serologic tests. RESULTS: Of the 57 scans considered negative at the standard acquisition, 13 (22.8%) became clearly positive at the delayed acquisition, and 6 (10.5%) became indeterminate at the delayed acquisition. Furthermore, 20 of 22 scans interpreted as indeterminate at the standard acquisition were considered positive because of clear perilesional (18)F-FDG uptake at the delayed acquisition. Thus, delayed acquisition changed the interpretation in 32.5% of cases. Moreover, of 44 patients treated by benzimidazoles and followed for more than 2 y by regular (18)F-FDG PET scans and specific AE serology, 11 (25%) presented pathologic (18)F-FDG uptake at the delayed acquisition but not at the standard one. In these patients, the treatment was continued despite negative results on standard (18)F-FDG PET and negative serologic findings. On the other hand, in 7 patients with negative delayed (18)F-FDG PET and negative serology, the treatment was safely interrupted with no evidence of disease recurrence during 8-37 mo (mean, 23 mo). CONCLUSION: Our study clearly demonstrated that delayed (18)F-FDG PET greatly facilitated the differentiation between active and inactive liver lesions in AE patients. Also, our results strongly suggested that the combination of delayed (18)F-FDG PET and specific serology would prevent most of the recurrences observed after premature interruption of the treatment based only on standard (18)F-FDG PET.