Editorial Radiopharmaceuticals in Nuclear Medicine: Recent ...downloads.hindawi.com/journals/bmri/2014/426892.pdf · dynamic PET measurements using F -FPCIT in normal adult subjects

EditorialRadiopharmaceuticals in Nuclear Medicine: RecentDevelopments 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, Ilha do Fundao, 21941-913 Rio de Janeiro, RJ, Brazil

2 Advanced Center Oncology Macerata (ACOM), Localita Cavallino, 62010 Montecosaro, 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 AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Nuclear medicine is returning to its origin by studyingmore and more metabolic signals using new positron orsingle-photon-emitting radiopharmaceuticals.The history ofnuclear medicine over the past 50 years highlights the stronglink between investments in chemistry and the developmentof radionuclides and radiolabeled compounds. In fact, onecan trace the major advances in nuclear medicine directlyto research in chemistry. These advances have had a majorimpact on the practice of health care. According to the Societyof NuclearMedicine, 20million nuclearmedicine proceduresusing radiopharmaceuticals and imaging instruments arecarried out in hospitals in the United States alone each yearto diagnose disease and to deliver targeted treatments. Thesetechniques have also been adopted by basic and clinicalscientists in different fields (infection, immunology, gas-troenterology, cardiology, oncology, neurology, psychiatry,and others) for diagnosis as well as for scientific tools.

Many groups of research are now developing radiophar-maceuticals as biomarkers for new drug targets to facilitatethe entry of their new drugs into the practice of healthcare and to objectively examine drug efficacy at a particulartarget relative to clinical outcome.This has created a demandfor new radiopharmaceuticals and a corresponding need forscientists who are trained to develop them.

The traditional lack of techniques suitable for in vivoimaging has induced a great interest in molecular imagingfor preclinical research. Nevertheless, its use spreads slowlydue to the difficulties to justify the high cost of the currentdedicated preclinical scanners. An alternative for lowering

the costs is to repurpose old clinical gamma-cameras to beused for preclinical imaging. In this paper P. Aguiar et al.have assessed the performance of a portable device that isworking coupled to a single-head clinical gamma-cameraand have presented their preliminary experience in severalsmall animal applications. Their findings, based on phantomexperiments and animal studies, provided an image quality,in terms of contrast-noise trade-off, comparable to dedicatedpreclinical pinhole-based scanners. They suggest that theirdevice can offer an opportunity for recycling the widespreadavailability of clinical gamma-cameras innuclear medicinedepartments to be used in small animal SPECT imagingcontributing to spreading of the use of preclinical imagingwithin institutions on tight budgets.

Molecular imaging using single-photon (gamma) imag-ing (SPECT) and positron emission tomography (PET) basedapproaches is promising tools for noninvasive diagnosisof acute allograft rejection (AR). Given the importance ofrenal transplantation and the limitation of available donors,detailed analysis of factors that affect transplant survival isimportant. Episodes of acute allograft rejection are a nega-tive prognostic factor for long-term graft survival. Invasivecore needle biopsies are still the gold standard in rejectiondiagnostics.Nevertheless, they are cumbersome to the patientand carry the risk of significant graft injury. Notably, theycannot be performed on patients taking anticoagulant drugs.Therefore, a noninvasive tool assessing the whole organ forspecific and fast detection of acute allograft rejection is desir-able. H. Pawelski et al. have reviewed SPECT- and PET-based

Hindawi Publishing CorporationBioMed Research InternationalVolume 2014, Article ID 426892, 3 pageshttp://dx.doi.org/10.1155/2014/426892

2 BioMed Research International

approaches for noninvasive molecular imaging-based diag-nostics of acute transplant rejection.

Nuclear cardiology has experienced exponential growthwithin the past four decadeswith converging capacity to diag-nose and influencemanagement of a variety of cardiovasculardiseases. SPECT myocardial perfusion imaging (MPI) withtechnetium-99m radiotracers or thallium-201 has dominatedthe field; however new hardware and software designs thatoptimize image quality with reduced radiation exposure arefuelling a resurgence of interest at the preclinical and clinicallevels to expand beyond MPI. Other imaging modalitiesincluding PET and MRI continue to emerge as powerfulplayers with an expanded capacity to diagnose a variety ofcardiac conditions. At the forefront of this resurgence is thedevelopment of novel target vectors based on an enhancedunderstanding of the underlying pathophysiological processin the subcellular domain. Molecular imaging with novelradiopharmaceuticals engineered to target a specific subcel-lular process has the capacity to improve diagnostic accu-racy and deliver enhanced prognostic information to altermanagement. O. O. Sogbein et al. have reviewed the recentadvancements in radiotracer development for SPECT andPET MPI, autonomic dysfunction, apoptosis, atheroscleroticplaques, metabolism, and viability. The relevant radiochem-istry, preclinical and clinical development, and molecularimaging with emerging modalities such as cardiac MRI andPET-MR have also been discussed.

Until recently, iodine-124 was not considered to bean attractive isotope for medical applications owing to itscomplex radioactive decay scheme, which includes severalhigh-energy gamma rays. However, its unique chemicalproperties and convenient half-life of 4.2 days indicated itwould be only a matter of time for its frequent application tobecome a reality. The development of new medical imagingtechniques, especially improvements in the technology ofPET such as the development of new detectors and signalprocessing electronics, has opened up new prospects for itsapplication.With the increasing use of PET inmedical oncol-ogy, pharmacokinetics, and drug metabolism, 124I-labeledradiopharmaceuticals are now becoming one of the mostuseful tools for PET imaging, and owing to the convenienthalf-life of I-124 they can be used in PET scanners far awayfrom the radionuclide production site.124Iodine (124I) is particularly attractive for in vivo

detection and quantification of longer-term biological andphysiological processes; the long half-life of 124I is especiallysuited for prolonged time in vivo studies of high molecularweight compounds uptake. Numerous small molecules andlarger compounds like proteins and antibodies have beensuccessfully labeled with 124I. Advances in radionuclideproduction allow the effective availability of sufficient quan-tities of 124I on small biomedical cyclotrons for molecularimaging purposes. Radioiodination chemistry with 124I relieson well-established radioiodine labeling methods, whichconsists mainly in nucleophilic and electrophilic substitutionreactions. G. L. Cascini et al. have discussed all iodineradioisotopes application focusing on 124I that seems to bethe most promising for its half-life, radiation emissions,

and stability, allowing several applications in oncological andnononcological fields.64Cu-Labeled molecules are promising imaging agents

for PET due to the favorable nuclear characteristics of theisotope (𝑡1/2 = 12.7 h, 𝛽+ 17.4%, 𝐸max = 0.656MeV, 𝛽−39%, 𝐸max = 0.573MeV) and its availability in high specificactivity.The longer physical half-life of 64Cu compared to 11C(𝑡1/2 = 20 min) and 18F (𝑡1/2 = 110 min) enables imaging atdelayed time points, which allows sufficient time for clear-ance from background tissues, resulting in increased imagecontrast, particularly for targeting agents that demonstratelong circulation times such as antibodies and nanoparticles.Moreover, 64Cu-based PET radiotracers have demonstratedefficacy for radioimmunotherapy comparable to that for thestrictly therapeutic radionuclide, 67Cu (𝑡1/2 = 61.5 h, 𝛽−100%, 𝐸max = 0.121MeV). Accordingly, 64Cu could be usedfor imaging and therapy concurrently.

Copper (Cu) is an important trace element in humans;it plays role as a cofactor for numerous enzymes and otherproteins crucial for respiration, iron transport, metabolism,cell growth, and hemostasis. Natural copper comprises twostable isotopes, 63Cu and 65Cu, and 5 principal radioisotopesfor molecular imaging applications (60Cu, 61Cu, 62Cu, and64Cu) and in vivo targeted radiation therapy (64Cu and 67Cu).The two potential ways to produce Cu radioisotopes concernthe use of the cyclotron or the reactor. A noncopper target isused to produce non-carrier-added Cu thanks to a chemicalseparation from the target material using ion exchangechromatography achieving a high amount of radioactivitywith the lowest possible amount of nonradioactive isotopes.In recent years Cu isotopes have been linked to antibodies,proteins, peptides, and nanoparticles for preclinical andclinical research; pathological conditions that influence Cumetabolism such as Menkes syndrome, Wilson disease,inflammation, tumor growth, metastasis, angiogenesis, anddrug resistance have been studied. A. N. Asabella et al. havediscussed all Cu radioisotopes application focusing on 64Cuand in particular its form 64CuCl

2that seems to be the most

promising for its half-life, radiation emissions, and stabilitywith chelators, allowing several applications in oncologicaland nononcological fields.

Although neurological ailments continue to be some ofthe main causes of disease burden in the world, currenttherapies such as pharmacological agents have limited poten-tial in the restoration of neural functions. Cell therapies,firstly applied to treat different hematological diseases, arenow being investigated in preclinical and clinical studiesfor neurological illnesses. However, the potential applica-tions and mechanisms for such treatments are still poorlycomprehended and are the focus of permanent research.In this setting, noninvasive in vivo imaging allows betterunderstanding of several aspects of stem cell therapies.Amongst the various methods available, radioisotope celllabeling has become one of the most promising since itpermits tracking of cells after injection by different routesto investigate their biodistribution. A significant increase inthe number of studies utilizing this method has occurred inthe last years. P. H. Rosado-de-Castro et al. have reviewed

BioMed Research International 3

the different radiopharmaceuticals, imaging techniques, andfindings of the preclinical and clinical reports published up tonow.Moreover, they have discussed the limitations and futureapplications of radioisotope cell labeling in the field of celltransplantation for neurological diseases.

W. Robeson et al. have demonstrated that, for dopamin-ergic radiotracers, 18F-FDOPA and 18F-FPCIT, the urinarybladder is the critical organ. As these tracers accumulate inthe basal ganglia (BG) with high affinity and long residencetimes, radiation dose to the BG may become significant,especially in normal control subjects. They have performeddynamic PET measurements using 18F-FPCIT in normaladult subjects to determine if in fact the BG, although nota whole organ but a well-defined substructure, receives thehighest dose. They have concluded that, for some normalsubjects studied with F-18 or long half-life radionuclide,the BG may exceed bladder dose and become the criticalstructure.

These papers represent important observations into dif-ferent topics related to recent developments for SPECTand PET studies. We hope that this special issue reachesresearches all over the world who deal with this field.

Acknowledgment

We would like to thank all the authors and reviewers thatmade this Special Issue possible.

Bianca GutfilenGianluca Valentini

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Editorial Radiopharmaceuticals in Nuclear Medicine: Recent ...downloads.hindawi.com/journals/bmri/2014/426892.pdf · dynamic PET measurements using F -FPCIT in normal adult subjects