Ahead of Print article withdrawn by publisher.
Ahead of Print article withdrawn by publisher.
Background: The expression of vesicular catecholamine transporters (VMAT1 and 2) in pheochromocytomas (PHEOs) and paragangliomas (PGLs) and the possible relationships with [18F]FDOPA PET/CT and [123I]MIBG scintigraphy uptake are unknown. Our purpose was to investigate possible correlations of either VMAT1 and VMAT2 expression with the functional imaging in patients with PHEOs and PGLs.
Methods: An observational 3-year time study was performed by enrolling 31 consecutive patients with PHEO (N.=17) or PGL (N.=14). They underwent the same diagnostic work-up; moreover, [123I]MIBG SPECT/CT (N.=20) and [18F]FDOPA PET/CT (N.=14) were performed in a subset of patients. After surgery, routine histology and semiquantitative analysis of VMAT1/VMAT2 immunoreactivity were carried out in all cases.
Results: VMAT1 immunoreactivity was found in all tumors, but two PHEOs. VMAT1 immunoreactivity was higher in PGLs than in PHEOs, though at not significant extent. Elevated VMAT2 immunoreactivity score was present in all but two negative tumors. Normal [123I]-MIBG uptake was independent from VMAT1/2 immunoreactivity. Patients undergoing [18F]FDOPA PET/CT showed a high score level of both VMATs and were detected by the technique in all cases.
Conclusions: VMAT1 and VMAT2 are highly expressed in most tumors, though VMAT1 immunoreactivity is apparently prevalent in PGLs as compared to PHEOs. Presence and expression of VMAT1 and VMAT2 are not limiting factors for MIBG uptake. The status of VMAT expression might help to understand why the more frequently used radiotracers do not always have the expected diagnostic performance. Finally, the present study points out the importance of developing new radiotracers with higher sensitivity, specificity and accuracy consequently reducing healthcare costs.
In the last few decades, the incidence and prevalence of neuroendocrine tumors has been increasing. The theragnostic approach, that allows the diagnosis and treatment of different neoplasms with the same ligand, is a typical nuclear medicine tool. Applied for years, is also pivotal in neuroendocrine tumors (NETs) where it has improved the diagnostic accuracy and the therapeutic efficacy with impact on patient's survival. Theragnostic also allows the identification of important prognostic factors such as tumor location and burden, presence of liver metastases and intensity of somatostatin receptors (SSTR) expression to consider in new and possibly combined studies to ameliorate patient's outcome. Moreover, the possibility to evaluate receptor expression even in non-NET malignancies has de facto widened the possible indications for PRRT. We believe that this innovative therapeutic approach will be implemented in next years by radiomics and biological tumors characterization to better address PRRT applications.
Precision medicine (or personalized medicine) is an intriguing, and still involving part of modern medicine. Theragnostics is a combination of therapies and diagnostics targeting pathophysiological processes at molecular level using radiopharmaceuticals. It is a valuable resource in efforts to implement precision medicine in clinical practice, but the theragnostic era poses an abundance of challenges. The aim of the present paper study was to analyze some of these challenges in the field of theragnostics, irrespective of their clinical applications. Three experts in this field discussed the balance between the demand, the costs of theragnostics, the need of appropriate infrastructures, and the opportunities for new developments in this area.
Aim: To assess the prognostic role of interim 18FFDGPET/CT in pediatric patients with Hodgkin's lymphoma (PHL).
Methods: Prospective analysis of 254 Saudi patients with pathologically proven PHL, they underwent interim 18F-FDG-PET/CT after 2 cycles of ABVD with baseline study, analysis of interim 18F-FDG-PET/CT was done visually according to the Deauville score (5-point score) as well as semi-quantitative analysis using maximum standardized uptake value (SUVmax), average SUV (SUVmean2.5 and SUVmean40). The parameters were calculated as absolute values and as percentages of difference between the initial and the interim hottest residual lesion. Follow-up was done for period of 2.9 years (range, 0.9 to 5.2 years). clinical outcomes were obtained from medical records.
Results: two hundred and twenty out of 254 children showed PET-ve interim while 34 were still PET+ve. Univariate analysis showed that the risk stratification, qualitative analysis of interim 18F-FDG-PET/CT were significant predictors for total actuarial survival (TAS) and disease free survival (DFS). Among the semiquantitative parameters, ΔSUVmean2.5 has the highest hazard ratio. In multivariate analysis, the current study revealed that the three above factors were important prognostic factors that can predict TAS and DFS. However, visual assessment of interim PET canceled the prognostic impact of ΔSUVmean2.5.
Conclusions: visual assessment of early interim 18F-FDG-PET/CT after 2 cycles of ABVD in PHL showed a very significant role in prediction ofTAS and DFS.
Primary and secondary hepatic tumors have a dramatic impact in oncology. Despite many advances in diagnosis and therapy, the management of hepatic malignancies is still challenging, ranging from various loco-regional approaches to system therapies. In this scenario, theragnostic approaches, based on the administration of a radiopharmaceuticals' pair, the first labeled with a radionuclide suitable for the diagnostic phase and the second one bound to radionuclide emitting particles for therapy, is gaining more and more importance. Selective internal radiation therapy (SIRT) with microspheres labeled with 90Y or 166Ho is widely used as a loco-regional treatment for primary and secondary hepatic tumors. While 166Ho presents both gamma and beta emission and can be therefore considered a real "theragnostic" agent, for 90Y-microspheres theragnostic approach is realized at the diagnostic phase through the utilization of macroaggregates of human albumin, labeled with 99mTc as "biosimilar" agent respect to microspheres. The aim of the present review was to cover theragnostic applications of 90Y/166Ho-labeled microspheres in clinical practice. Furthermore, we report the preliminary data concerning the potential role of some emerging theragnostic biomarkers for hepatocellular carcinoma, such as glypican-3 (GPC3) and prostate specific membrane antigen (PSMA).
In locally or locally advanced solid tumors, surgery still remains a fundamental treatment method. However, conservative resection is associated with high collateral damage and functional limitations of the patient. Furthermore, the presence of residual tumor tissue following conservative surgical treatment is currently a common cause of locally recurrent cancer or of distant metastases. Reliable intraoperative detection of small cancerous tissue would allow surgeons to selectively resect malignant areas: this task can be achieved by means of image-guided surgery, such as beta radioguided surgery (RGS). In this paper, a comprehensive review of beta RGS is given, starting from the physical principles that differentiate beta from gamma radiation, that already has its place in current surgical practice. Also, the recent clinical feasibility of using Cerenkov radiation is discussed. Despite being first proposed several decades ago, only in the last years a remarkable interest in beta RGS has been observed, probably driven by the diffusion of PET radiotracers. Today several different approaches are being pursued to assess the effectiveness of such a technique, including both beta+ and beta- emitting radiopharmaceuticals. Beta RGS shows some peculiarities that can present it as a very promising complementary technique to standard procedures. Good results are being obtained in several tests, both ex vivo and in vivo. This might however be the time to initiate the trials to demonstrate the real clinical value of these technologies with seemingly clear potential.
Recent technical advances and implementation of novel radiotracers have further increased the potential of radioguided surgery for a broad variety of malignancies. Indeed, the possibilities for future applications of novel radiotracers in diverse oncological strategies has become more promising than ever. This literature review aims to provide a contemporary update on a selected group of radiotracers and evaluates the usability of radioguided surgery and sentinel node procedures, focusing on most promising advances. For example, the impact of targeted radiotracers on prostate specific membrane antigen (PSMA), CD206 receptor-targeted agents (99mTc-tilmanocept), and hybrid tracers adding fluorescence to radioguidance (ICG-99mTc-nanocolloid) as well as targeting hypoxia-induced carbonic anhydrase IX (CAIX) will be covered. Furthermore, future outlooks on the implementation of gold nanoparticles (AuNP's), but also technical advances in improved radiotracer detection by hybrid gamma devices will be discussed.
It is well known nowadays that radioactivity can destroy the living cells it interacts with. It is therefore unsurprising that radioactive sources, such as iodine-125, were historically developed for treatment purposes within radiation oncology with the goal of damaging malignant cells. However, since then, new techniques have been invented that make creative use of the same radioactivity properties of these sources for medical applications. Here, we review two distinct kinds of therapeutic uses of radioactive sources with applications to prostate, cervical, and breast cancer: brachytherapy and radioactive seed localization. In brachytherapy (BT), the radioactive sources are used for internal radiation treatment. Current approaches make use of real-time image guidance, for instance by means of magnetic resonance imaging, ultrasound, computed tomography, and sometimes positron emission tomography, depending on clinical availability and cancer type. Such image-guided BT for prostate and cervical cancer presents a promising alternative and/or addition to external beam radiation treatments or surgical resections. Radioactive sources can also be used for radio-guided tumor localization during surgery, for which the example of iodine-125 seed use in breast cancer is given. Radioactive seed localization (RSL) is increasingly popular as an alternative tumor localization technique during breast cancer surgery. Advantages of applying RSL include added flexibility in the clinical scheduling logistics, an increase in tumor localization accuracy, and higher patient satisfaction; safety measures do however have to be employed. We exemply the implementation of RSL in a clinic through our experiences at the Netherlands Cancer Institute.
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