[Show abstract][Hide abstract] ABSTRACT: Positron emission tomography (PET) with [(18)F]fluoro-2-deoxy-D-glucose (FDG) has proven to be a valuable diagnostic modality in various diseases. Its accuracy has been improved with the hybrid PET/computed tomography (CT) technique because of precise anatomic location of areas of abnormal FDG accumulation. This integrated PET/CT modality has been widely adopted, particularly in oncology. This paper reviews the role of FDG-PET/CT imaging in breast cancer, non-small-cell lung cancer, colorectal cancer, head and neck cancer as well as lymphoma on the basis of recent key articles. Special attention is paid to preoperative diagnostic workup, evaluation of treatment response and survival prognosis. Experience from specialized centers indicates that there is strong evidence for the clinical effectiveness of FDG-PET/CT in staging, restaging and the prediction of response to therapy in the above-mentioned malignancies. It is concluded that this imaging modality contributes considerably to improved patient management and paves the way to personalize cancer treatment in a cost-effective way.
Medical Principles and Practice 01/2013; · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Immunofluorescence that permits the detection of nuclear targets specific to DNA damage signalling and repair have completely renewed the approach of individual radiosensitivity. It is a concern in radiotherapy in which radiosensitivity is responsible for the development of adverse side-effects in normal tissues in absence of any mistake in the dose delivery. Furthermore, individual radiosensitivity at low-dose has been recently demonstrated in human mammary epithelium exposed ex vivo in the conditions of mammographic screening. Although these results do not demonstrate directly the existence of mutagenesis, they indicate a possible link between cancer proneness and radiosensitivity. Hence, individual radiosensitivity is a real concern for public health since 5-15% of the population may be concerned and radiosensitive individuals generally show higher cancer risk than the rest of the population. Thus, individual radiosensitivity is a key issue to be addressed in future recommendations of the radioprotection system.
[Show abstract][Hide abstract] ABSTRACT: Over the past two decades technical advances and improvements have made computed tomography (CT) a valuable and essential tool in the array of diagnostic imaging modalities. CT uses ionizing radiation (X-rays) which may damage DNA and increase the risk of carcinogenesis. This is especially pertinent in pediatric CT as children are more radiosensitive and have a longer life expectancy than adults. The purpose of this paper is to review and elucidate the potential harmful effects of ionizing radiation in terms of solid cancer induction from pediatric CT scanning. In the light of scientific and technical developments, we will also discuss the possible strategies and ongoing efforts to reduce CT radiation exposure in pediatric patients. In this context, we will not ignore the fact that a well-justified CT scan may exceed its risk and have a favorable impact.
Medical Principles and Practice 03/2012; 21(6):508-15. · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The considerable rise of computed tomography (CT) procedures over the past few decades has urged responsible authorities and researchers to evaluate the risk of carcinogenesis in the population in relation to the radiation dose delivered to the patient. A single patient undergoing CT may receive a radiation equivalent dose that varies between about 2 mSv (head ) to about 20 mSv (CT-based coronary angiography). Whereas the latter represents a substantial dose delivered to one patient it is, however, population-wise far below the area of the so-called low doses, i.e. 50 mSv in children and 100 mSv in adults. While at effective doses above 50 mSv the risk of cancer induction increases linearly with dose, this dose-response relation has not been demonstrated at doses below 50 mSv. Below 50 mSv no convincing epidemiological evidence for cancer risk exists. Calculations on this risk are based on scientifically questionable, if not invalid, extrapolations of data from higher doses. However, the failure to demonstrate that a risk of cancer exists does not mean that there is no risk. This paper summarizes the data mentioned in various articles from recent literature discussing cancer risks due to CT and puts the results of these studies in perspective of current scientific knowledge in the field of radiation protection. For this we follow the lead of the ICRP and UNSCEAR. Furthermore, we review the strategies and efforts of various national and international bodies and manufacturers of CT apparatus to lower the radiation dose to the patient.
[Show abstract][Hide abstract] ABSTRACT: The lower occurrence of cancer and cardiovascular disease in the population around the Mediterranean basin has been linked to the dietary habits of the region. Indeed, this so-called Mediterranean diet is essentially different from the diets consumed in Western and Northern European countries and is rich in nuts, fruits, vegetables, legumes, whole-wheat bread, fish, and olive oil, with moderate amounts of red wine, which is mainly consumed during meals. Although a variety of cultural and religious traditions exist among the peoples of the Mediterranean area, olive oil, fish, and red wine hold a traditional and central position in the culinary routines of the region. The components of the diet contain an ample source of molecules with antioxidant and anti-inflammatory actions, among which omega-3 fatty acids, oleic acid, and phenolic compounds hold a prominent place. This review will summarize the results of important epidemiological studies that have investigated the protective effect of fish and olive oil on the risk of breast, prostate, and colorectal cancer and of wine on the risk of cardiovascular disease. The present review also aims to elucidate the various mechanisms by which various dietary components exhibit their beneficial action. In this respect, emphasis will be placed on the properties of omega-3 fatty acids from fish, oleic acid from olive oil, and phenolic compounds from olive oil and red wine.
Medical Principles and Practice 01/2011; 20(2):103-11. · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Molecular imaging techniques are increasingly being used as valuable tools in the drug development process. Radionuclide-based imaging modalities such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET) have proven to be useful in phases ranging from preclinical development to the initial stages of clinical testing. The high sensitivity of these imaging modalities makes them particularly suited for exploratory investigational new drug (IND) studies as they have the potential to characterize in vivo pharmacokinetics and biodistribution of the compounds using only a fraction of the intended therapeutic dose (microdosing). This information obtained at an early stage of clinical testing results in a better selection among promising drug candidates, thereby increasing the success rate of agents entering clinical trials and the overall efficiency of the process. In this article, we will review the potential applications of SPECT imaging in the drug development process with an emphasis on its applications in exploratory IND studies.
Advanced drug delivery reviews 10/2010; 63(7):547-54. · 11.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Early assessment of the efficacy of treatment is important in patients with breast cancer, whose routine adjuvant regimen frequently includes chemotherapy. Irrespective of the exact mechanisms involved in induction, the common early phenotypic marker of apoptosis is the expression on the outer cell membrane surface of phosphatidylserine, which avidly binds annexin V. (99m)Tc-labeled annexin V has been proposed for in vivo scintigraphic detection of apoptosis, albeit with contradicting results. This study was performed to define the time course of apoptosis induced by the chemotherapeutic agent paclitaxel in a model of virus-induced murine breast cancer.
The RIII virus induces an estrogen-dependent, slow-growing breast cancer; BALB-c/cRIII female mice with breast tumors averaging 10 mm were studied, both in baseline conditions and at various times after the intravenous administration of paclitaxel (equivalent to a human dose of 20 mg/70 kg of body weight). The biodistribution of (99m)Tc-annexin V was evaluated at baseline and then at 1, 3, 6, and 24 h after paclitaxel administration. Apoptotic and antiapoptotic markers were also evaluated in tumor samples obtained at the same time points: DNA breaks (terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling [TUNEL]), active caspase-3, apoptosis-inducing factor, and Bcl-2 protein.
Baseline uptake of (99m)Tc-annexin V in breast tumors was about 2-fold higher than the uptake in normal breast tissue (demonstrating some ongoing apoptosis); tracer uptake increased at 1 and 3 h after paclitaxel administration (to almost double the baseline value) and then declined to levels even lower than baseline. Although no activation of the apoptosis-inducing factor mechanism was detected, a peak in TUNEL-positive tumor cells was reached 3 h after paclitaxel administration (to more than 6-fold the baseline level). The antiapoptotic marker Bcl-2 exhibited a biphasic pattern, with a maximum drop at 3 h, followed by return toward baseline levels at 6 h.
These results define the time course of various biologic events taking place in this model of murine breast cancer after a proapoptotic insult (single-dose paclitaxel). Although confirming that in vivo uptake of (99m)Tc-annexin V reflects the degree of apoptosis, the study also suggests that the apoptotic response to antitumor therapy may differ from tumor type to tumor type. Therefore, contradicting results previously reported may depend on an inadequate time window chosen for imaging with (99m)Tc-annexin V.
Journal of Nuclear Medicine 05/2010; 51(5):775-81. · 5.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The tumor-associated structure N-acetyl-galactosamine-O-Ser/Thr (Tn antigen), which is overexpressed in various tumor cell types, notably of the breast, ovary and colon, is an interesting determinant that is useful for cancer diagnosis and follow-up. The aim of this research was to study different assay strategies in order to determine the most sensitive system for further application in epitope characterization and binding assessment. The tetrameric isolectin obtained from Vicia villosa seeds (VVLB(4)) shows high affinity for the tumor-associated structure. A monoclonal antibody against VVLB(4), MabVV(34), was generated, and the interaction between MabVV(34) and VVLB(4) was studied by means of binding and inhibition assays. Several synthetic peptides (10 amino acid sequences) designed from the amino acid sequence of VVLB(4) and obtained from trypsin digestion were tested to determine which amino acids were involved in the interaction between MabVV(34) and VVLB(4). The further unraveling of this epitope was investigated by inhibition using designed synthetic peptides as well as mixtures mimicking variable density effect. Under the experimental circumstances, MabVV(34) was able to inhibit the binding of VVLB(4) to Tn. Two of the four peptide sequences assayed showed better inhibition properties. Finally, mixtures containing these selected sequences allowed the evaluation of binding and inhibition as a function of Tn density. We conclude that the present study facilitates the further development of a specific Tn marker and may contribute to the development of Tn-like radiolabelled peptides or Tn-specific radiolabelled fragments providing a highly selective tool for cancer diagnosis and treatment. This strategy may contribute to characterize the new generation of radiopharmaceuticals for diagnosis and therapy based on biomolecules like antibodies, fragments or peptides, whose application is directly guided by their specific molecular recognition.
Nuclear Medicine and Biology 05/2010; 37(4):453-8. · 2.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Microdosing provides a tool to enhance drug development by initiating human studies prior to Phase I studies. The purpose is to assist in the go versus no-go decision-making process and to eliminate early ineffective compounds from the drug pipeline. Selection of multiple potential leads can be performed at the clinical stage instead of in preclinical studies. The microdosing approach can be easily used for a molecularly targeted potential drug compound with a known mechanism of action. It provides useful data regarding accessibility and biodistribution that can be used in many estimations benefiting the development of the molecule. In addition, steady state and genetic investigations are becoming possible. Microdosing has a sparing effect on timelines and costs, however, the real importance is not yet known because, although it is known to be widely performed, only a few original reports have been published.