Presse Medicale最新文献

Given the more widespread use of conventional imaging techniques such as magnetic resonance imaging or computed tomography, recent years have witnessed an increased rate of incidental findings in the adrenal gland and those adrenal masses can be either of benign or malignant origin. In this regard, routinely conducted morphological imaging cannot always reliably distinguish between cancerous and noncancerous lesions. As such, those incidental adrenal masses trigger further diagnostic work-up, including molecular functional imaging providing a non-invasive read-out on a sub-cellular level. For instance, [¹⁸F]FDG positron emission tomography (PET) as a marker of glucose consumption has been widely utilized to distinguish between malignant vs benign adrenal lesions. In addition, more adrenal cortex-targeted radiotracers for PET or single photon emission computed tomography have entered the clinical arena, e.g., Iodometomidate or IMAZA, which are targeting CYP11B enzymes, or Pentixafor identifying CXCR4 in adrenal tissue. All these tracers are used for diagnosing tumors deriving from the adrenal cortex. Furthermore, radiolabeled MIBG, DOPA, and DOTATOC/-TATE are radiotracers that are quite helpful in detecting pheochromocytomas originating from the adrenal medulla. Of note, after having quantified the retention capacities of the target in-vivo, such radiotracers have the potential to be used as anti-cancer therapeutics by using their therapeutic equivalents in a theranostic setting. The present review will summarize the current advent of established and recently introduced molecular image biomarkers for investigating adrenal masses and highlight its transformation beyond providing functional status towards image-guided therapeutic approaches, in particular in patients afflicted with adrenocortical carcinoma.

Over the past twenty years, nuclear medicine has enhanced the role of functional imaging in cancerology. A major milestone was achieved in the early 2000s with widespread availability of the positron emitter tracer 18F- deoxyglucose (FDG) and the introduction of hybrid imagers, i.e. positron imagers coupled with an X CT, providing anatomical landmarks and potently contributing to attenuation and scatter correction of the images. Other technical advances have progressively increased the quality of positron images. To date, the most widely used tracer remains FDG, which is highly beneficial in terms of sensitivity and specificity in detection of tumor sites, also providing biological information on tumors and early evaluation of treatment response for most cancers. Other highly specific tracers have been developed and are now routinely used for pheochromocytoma and paraganglioma, neuroendocrine tumors, and prostate cancer.

Biological Radiotherapy has two aspects: Internal radiotherapy consisting in administration of a tumor-specific molecule radiolabeled with an isotope delivering an adequate radiation dose to the targeted tumor sites (on the model of thyroid cancer treated with radioiodine) and external radiotherapy designed to determine tumor volume, assess response and to dose radiation according to the tumor characteristics shown by functional imaging.

Radioiodine uptake (RAIU) test with iodine-123 (Na[¹²³I]I) or iodine-131 (Na[¹³¹I]I) enables accurate evaluation and quantification of iodine uptake and kinetics within thyroid cells. Thyroid Scintigraphy (TS) employing Na[¹²³I]I or ^99mTc-pertechnetate (Na[^99mTc]TcO₄) provides information regarding the function and topographical distribution of thyroid cells activity, including detection and localization of ectopic thyroid tissue. Destructive thyrotoxicosis is characterized by low RAIU with scintigraphically reduced radiotracer activity in the thyroid tissue, while productive thyrotoxicosis (i.e. hyperthyroidism “stricto sensu”) is characterized by high RAIU with scintigraphically diffuse (i.e. Graves’ Disease, GD and diffuse thyroid autonomy) or focal (i.e. autonomously functioning thyroid nodules, AFTN) overactivity. Accordingly, RAIU and/or TS are widely used to differentiate different causes of thyrotoxicosis. In addition, several radiopharmaceuticals are also available to help differentiate benign from malignant thyroid nodules and inform clinical decision-making: scintigraphic identification of AFTNs obviate fine-needle aspiration (FNA) biopsy, and [^99mTc]Tc-hexakis-(2‑methoxy-2-isobutyl isonitrile ([^99mTc]Tc-MIBI) and/or ¹⁸F-fluoro-d-glucose ([¹⁸F]FDG) may complement the work-up of cytologically indeterminate “cold” nodules for reducing the need for diagnostic lobectomies/thyroidectomies. Finally, RAIU studies are also useful for calculating the administered therapeutic activity of Na[¹³¹I]I to treat hyperthyroidism and euthyroid multinodular goiter. All considered, thyroid molecular imaging allows functional characterization of different thyroid diseases, even before clinical symptoms become manifest, and remains integral to the management of such conditions. Our present paper summarizes basic concepts, clinical applications, and potential developments of thyroid molecular imaging in patients affected by thyrotoxicosis and thyroid nodules.

Molecular imaging, which uses molecular targets due to the overexpression of specific peptide hormone receptors on the tumour surface, has become an indispensable diagnostic technique.

Neuroendocrine neoplasms (NENs) especially differentiated NENs or neuroendocrine tumours (NETs) are a rare group of heterogeneous tumours, characterized by the expression of hormone receptors on the tumour cell surface. This property makes them receptive to diagnostic and therapeutic approaches (theranostics) using radiolabelled peptides.

Amongst the known hormone receptors, somatostatin receptors (SSTR) are expressed on the majority of NETs and are therefore the most relevant receptors for theranostic approaches. Current research aims to medically upregulate their expression, while other focuses are on the use of different radiopeptides (64Cu and 67Cu) or somatostatin-antagonists instead of the established somatostatin agonists.

The GLP-1 receptor is another clinically relevant target, as GLP-1-R imaging has become the new standard for the localisation of insulinomas. For staging and prognostic evaluation in dedifferentiated NENs, 18F-FDG-imaging is useful, but lacks a therapeutic counterpart. Further options for patients with insufficient expression of SSTR involve metaiodobenzylguanidine (MIBG) and the molecular target C-X-C motif chemokine receptor-4 (CXCR4). New targets such as the glucose-dependant insulinotropic polypeptide receptor (GIPR) and the fibroblast activation protein (FAP) have been identified in NENs recently and await further evaluation.

For medullary thyroid cancer 18-F-DOPA imaging is standard, however this technique is rather second line for other NENs. In this area, the discovery of minigastrin, which targets the cholecystokinin-2 (CCK2) receptors in medullary thyroid carcinoma and foregut NENs, may improve future management.

This review aims to provide an overview of the most commonly used functional imaging modalities for theranostics in NENs today and in the possible future.

During the last 20 years, cardiac imaging has drastically evolved. Positron emission tomography (PET), fast three-dimensional (3D) imaging with the latest generations of echocardiography & multi-detector computed tomography (CT), stress perfusion assessed by magnetic resonance imaging (MRI), blood flow analysis using four-dimensional (4D) flow MRI, all these techniques offer new trends for optimal noninvasive functional cardiac imaging. Dynamic functional imaging is obtained by acquiring images of the heart at different phases of the cardiac cycle, allowing assessment of cardiac motion, function, and perfusion. Between CT and Cardiac MRI (CMR), CMR has the best temporal resolution, which is suitable for functional imaging while cardiac CT provides higher spatial resolution with isotropic data that have an identical resolution in the three dimensions of the space. The latest generations of CT scanners enable whole heart assessment in one beat, offering also an acceptable temporal resolution with the possibility to display the images in a dynamic mode. Another rapidly growing technique using functional and molecular imaging for the assessment of biological and metabolic pathways is the PET using radio-labeled tracers. Meanwhile, the oldest cardiac imaging tool with doppler ultrasound technology has never stopped evolving. Echocardiography today performs 3D imaging, stress perfusion, and myocardial strain assessment, with high temporal resolution. It still is the first line and more accessible exam for the patient. These different modalities are complementary and may be even combined into PET-CT or PET-MRI. The ability to combine the functional/molecular data with anatomical images may implement a new dimension to our diagnostic tools.

In order to explore pituitary adenoma (PA), magnetic resonance imaging (MRI) remains the cornerstone. However, there are some limitations and MRI can be non-conclusive. The development of additional imaging modalities like nuclear medicine explorations may help to confirm PA diagnosis, guide management and follow up. Nuclear medicine uses radiopharmaceuticals for imaging with single photon emission computed tomography (SPECT), or positron emission tomography (PET), coupled to CT scan. Radiopharmaceuticals products target specific cellular elements which allow to explore several biological pathways. Nuclear medicine may also be used for therapeutic purposes and recent developments of approach based on Peptide Receptor Radionuclide Therapy (PRRT) for treatment of aggressive PA and pituitary carcinoma will be reviewed. Several radiotracers have been studied in the context of PA, and the aim of this paper is to discuss their respective performances and clinical interest.

Once hyperparathyroidism has been proven, the goal of parathyroid functional imaging is to identify one or more pathological glands in view of guiding a possibly targeted surgical procedure, while maximizing the chances for recovery. Currently, parathyroid radionuclide imaging is based on two techniques, parathyroid scintigraphy and ¹⁸F-fluorocholine - positron emission tomography (PET).

The main radiopharmaceutical in scintigraphy is ^99mTc-sestamibi, which can be used alone, in the dual-phase parathyroid scan, or in comparison with a thyroid radiotracer, pertechnetate (NaTcO₄) or iodine 123 (dual-tracer method). The acquisitions can be planar and/or tomographic (SPECT). It is now recognized that the ^99mTc-sestamibi - iodine 123 dual-tracer method is more efficient than the dual-phase scan, while SPECT-CT improves the sensitivity and specificity of the scintigraphy. This imaging and cervical ultrasonography are considered to be the two first-line reference techniques in preoperative assessment of hyperparathyroidism.

More recently developed, ¹⁸F-fluorocholine detected by PET-CT has shown excellent performance, at least equal to that of scintigraphy. Initially considered as a second-line technique, its advantages over scintigraphy have prompted some authors to suggest it as the only examination to be performed in preoperative assessment of hyperparathyroidism. That said, due to a lack of specificity in ¹⁸F-fluorocholine uptake, which has been observed on inflammatory lesions and, particularly, in the mediastinal lymph nodes, and given the absence of simultaneous comparison of thyroid function, this strategy remains contested, and possibly reserved for patients without any associated thyroid pathology; large-scale evaluation would be justified.

Functional imaging plays a central role in the management of thyroid cancer patients.

In patients with a differentiated thyroid cancer (DTC), radioactive iodine (RAI) is used mostly with a therapeutic intent, either post-operatively or as the first line systemic treatment in patients with known structural disease. A whole body scan is performed a few days after the RAI administration, and this procedure is very sensitive to detect all tumor foci with RAI uptake. PET/CT with ¹⁸F-FDG complements the use of RAI at the initial evaluation of patients with high-risk DTC, during follow-up in those with rising serum thyroglobulin levels over time, for the work-up of patients with documented structural disease and for assessing the efficacy of focal or systemic treatment modalities. ¹⁸F-FDG uptake is a prognostic indicator in all these clinical conditions. A dosimetric approach with ¹²⁴I PET/CT showed encouraging results.

Several functional imaging modalities are currently available for medullary thyroid carcinoma (MTC) patients. ¹⁸F-FDG-PET/CT may be sensitive in MTC patients with high FDG uptake that signals aggressive disease. ¹⁸F-DOPA is the most sensitive imaging technique to visualize small tumor foci, and is also highly specific in patients with a known MTC, but should be complemented by a CT scan of the chest and by a MRI of the liver to detect small metastases.