Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 426892, 3 pages http://dx.doi.org/10.1155/2014/426892

Editorial Radiopharmaceuticals in Nuclear Medicine: Recent Developments for SPECT and PET Studies

Bianca Gutfilen1 and Gianluca Valentini2 1 Department of Radiology, Universidade Federal do Rio de Janeiro, Hospital Universitario´ Clementino Fraga Filho, Rua Professor Rodolpho Rocco, 255 Cidade Universitaria,IlhadoFund´ ao,˜ 21941-913 Rio de Janeiro, RJ, Brazil 2 Advanced Center Oncology Macerata (ACOM), LocalitaCavallino,62010Montecosaro,Italy`

Correspondence should be addressed to Bianca Gutfilen; [email protected]

Received 6 November 2014; Accepted 6 November 2014; Published 21 December 2014

Copyright © 2014 B. Gutfilen and G. Valentini. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Nuclear medicine is returning to its origin by studying the costs is to repurpose old clinical gamma-cameras to be more and more metabolic signals using new positron or used for preclinical imaging. In this paper P. Aguiar et al. single-photon-emitting radiopharmaceuticals. The history of have assessed the performance of a portable device that is nuclear medicine over the past 50 years highlights the strong working coupled to a single-head clinical gamma-camera link between investments in chemistry and the development and have presented their preliminary experience in several of radionuclides and radiolabeled compounds. In fact, one small animal applications. Their findings, based on phantom can trace the major advances in nuclear medicine directly experiments and animal studies, provided an image quality, to research in chemistry. These advances have had a major in terms of contrast-noise trade-off, comparable to dedicated impact on the practice of health care. According to the Society preclinical pinhole-based scanners. They suggest that their of Nuclear Medicine, 20 million nuclear medicine procedures device can offer an opportunity for recycling the widespread using radiopharmaceuticals and imaging instruments are availability of clinical gamma-cameras innuclear medicine carried out in hospitals in the United States alone each year departments to be used in small animal SPECT imaging to diagnose disease and to deliver targeted treatments. These contributing to spreading of the use of preclinical imaging techniques have also been adopted by basic and clinical within institutions on tight budgets. scientists in different fields (infection, immunology, gas- Molecular imaging using single-photon (gamma) imag- troenterology, cardiology, oncology, neurology, psychiatry, ing (SPECT) and positron emission tomography (PET) based and others) for diagnosis as well as for scientific tools. approaches is promising tools for noninvasive diagnosis Many groups of research are now developing radiophar- of acute allograft rejection (AR). Given the importance of maceuticals as biomarkers for new drug targets to facilitate renal transplantation and the limitation of available donors, the entry of their new drugs into the practice of health detailed analysis of factors that affect transplant survival is care and to objectively examine drug efficacy at a particular important. Episodes of acute allograft rejection are a nega- target relative to clinical outcome. This has created a demand tive prognostic factor for long-term graft survival. Invasive for new radiopharmaceuticals and a corresponding need for core needle biopsies are still the gold standard in rejection scientists who are trained to develop them. diagnostics. Nevertheless, they are cumbersome to the patient The traditional lack of techniques suitable for in vivo and carry the risk of significant graft injury. Notably, they imaging has induced a great interest in molecular imaging cannot be performed on patients taking anticoagulant drugs. for preclinical research. Nevertheless, its use spreads slowly Therefore, a noninvasive tool assessing the whole organ for due to the difficulties to justify the high cost of the current specific and fast detection of acute allograft rejection is desir- dedicated preclinical scanners. An alternative for lowering able. H. Pawelski et al. have reviewed SPECT- and PET-based 2 BioMed Research International approaches for noninvasive molecular imaging-based diag- and stability, allowing several applications in oncological and nostics of acute transplant rejection. nononcological fields. 64 Nuclear cardiology has experienced exponential growth Cu-Labeled molecules are promising imaging agents within the past four decades with converging capacity to diag- for PET due to the favorable nuclear characteristics of the nose and influence management of a variety of cardiovascular isotope (𝑡1/2 = 12.7 h, 𝛽+17.4%,𝐸max = 0.656 MeV, 𝛽− diseases. SPECT myocardial perfusion imaging (MPI) with 39%, 𝐸max = 0.573 MeV) and its availability in high specific 64 11 technetium-99m radiotracers or thallium-201 has dominated activity. The longer physical half-life of Cu compared to C the field; however new hardware and software designs that (𝑡1/2 = 20 min) and 18F (𝑡1/2 = 110 min) enables imaging at optimize image quality with reduced radiation exposure are delayed time points, which allows sufficient time for clear- fuelling a resurgence of interest at the preclinical and clinical ance from background tissues, resulting in increased image levels to expand beyond MPI. Other imaging modalities contrast, particularly for targeting agents that demonstrate including PET and MRI continue to emerge as powerful long circulation times such as and nanoparticles. 64 players with an expanded capacity to diagnose a variety of Moreover, Cu-based PET radiotracers have demonstrated cardiac conditions. At the forefront of this resurgence is the efficacy for radioimmunotherapy comparable to that for the 67 development of novel target vectors based on an enhanced strictly therapeutic radionuclide, Cu (𝑡1/2 = 61.5 h, 𝛽− 64 understanding of the underlying pathophysiological process 100%, 𝐸max = 0.121 MeV). Accordingly, Cu could be used in the subcellular domain. Molecular imaging with novel for imaging and therapy concurrently. radiopharmaceuticals engineered to target a specific subcel- Copper (Cu) is an important trace element in humans; lular process has the capacity to improve diagnostic accu- it plays role as a cofactor for numerous enzymes and other racy and deliver enhanced prognostic information to alter proteins crucial for respiration, iron transport, metabolism, management. O. O. Sogbein et al. have reviewed the recent growth, and hemostasis. Natural copper comprises two 63 65 advancements in radiotracer development for SPECT and stable isotopes, Cu and Cu, and 5 principal radioisotopes 60 61 62 PET MPI, autonomic dysfunction, apoptosis, atherosclerotic for molecular imaging applications ( Cu, Cu, Cu, and plaques, metabolism, and viability. The relevant radiochem- 64 64 67 Cu) and in vivo targeted ( Cu and Cu). istry, preclinical and clinical development, and molecular The two potential ways to produce Cu radioisotopes concern imaging with emerging modalities such as cardiac MRI and the use of the cyclotron or the reactor. A noncopper target is PET-MR have also been discussed. used to produce non-carrier-added Cu thanks to a chemical Until recently, iodine-124 was not considered to be separation from the target material using ion exchange an attractive isotope for medical applications owing to its chromatography achieving a high amount of radioactivity complex radioactive decay scheme, which includes several with the lowest possible amount of nonradioactive isotopes. high-energy gamma rays. However, its unique chemical In recent years Cu isotopes have been linked to antibodies, properties and convenient half-life of 4.2 days indicated it proteins, peptides, and nanoparticles for preclinical and would be only a matter of time for its frequent application to clinical research; pathological conditions that influence Cu become a reality. The development of new metabolism such as Menkes syndrome, Wilson disease, techniques, especially improvements in the technology of inflammation, tumor growth, metastasis, angiogenesis, and PET such as the development of new detectors and signal drug resistance have been studied. A. N. Asabella et al. have processing electronics, has opened up new prospects for its 64 discussed all Cu radioisotopes application focusing on Cu application. With the increasing use of PET in medical oncol- 64 124 and in particular its form CuCl2 that seems to be the most ogy, pharmacokinetics, and drug metabolism, I-labeled promising for its half-life, radiation emissions, and stability radiopharmaceuticals are now becoming one of the most with chelators, allowing several applications in oncological useful tools for PET imaging, and owing to the convenient and nononcological fields. half-life of I-124 they can be used in PET scanners far away Although neurological ailments continue to be some of from the radionuclide production site. 124 124 the main causes of disease burden in the world, current Iodine ( I) is particularly attractive for in vivo therapies such as pharmacological agents have limited poten- detection and quantification of longer-term biological and 124 tial in the restoration of neural functions. Cell therapies, physiological processes; the long half-life of Iisespecially firstly applied to treat different hematological diseases, are suited for prolonged time in vivo studies of high molecular now being investigated in preclinical and clinical studies weight compounds uptake. Numerous small molecules and for neurological illnesses. However, the potential applica- larger compounds like proteins and antibodies have been 124 tions and mechanisms for such treatments are still poorly successfully labeled with I. Advances in radionuclide comprehended and are the focus of permanent research. production allow the effective availability of sufficient quan- In this setting, noninvasive in vivo imaging allows better 124 tities of Ionsmallbiomedicalcyclotronsformolecular understanding of several aspects of stem cell therapies. 124 imaging purposes. Radioiodination chemistry with Irelies Amongst the various methods available, radioisotope cell on well-established radioiodine labeling methods, which labeling has become one of the most promising since it consists mainly in nucleophilic and electrophilic substitution permits tracking of cells after injection by different routes reactions. G. L. Cascini et al. have discussed all iodine to investigate their biodistribution. A significant increase in 124 radioisotopes application focusing on Ithatseemstobe the number of studies utilizing this method has occurred in the most promising for its half-life, radiation emissions, thelastyears.P.H.Rosado-de-Castroetal.havereviewed BioMed Research International 3 the different radiopharmaceuticals, imaging techniques, and findings of the preclinical and clinical reports published up to now.Moreover,theyhavediscussedthelimitationsandfuture applications of radioisotope cell labeling in the field of cell transplantation for neurological diseases. W. Robeson et al. have demonstrated that, for dopamin- ergic radiotracers, 18F-FDOPA and 18F-FPCIT, the urinary bladder is the critical organ. As these tracers accumulate in thebasalganglia(BG)withhighaffinityandlongresidence times, radiation dose to the BG may become significant, especially in normal control subjects. They have performed dynamic PET measurements using 18F-FPCIT in normal adult subjects to determine if in fact the BG, although not a whole organ but a well-defined substructure, receives the highest dose. They have concluded that, for some normal subjects studied with F-18 or long half-life radionuclide, the BG may exceed bladder dose and become the critical structure. These papers represent important observations into dif- ferent topics related to recent developments for SPECT and PET studies. We hope that this special issue reaches researches all over the world who deal with this field.

Acknowledgment Wewouldliketothankalltheauthorsandreviewersthat made this Special Issue possible. Bianca Gutfilen Gianluca Valentini