Current Radiopharmaceuticals - Volume 7, Issue 1, 2014

Since the conception of the journal Current Radiopharmaceuticals in January 2008, we have been inundated with a variety of research articles ranging from discussions on the use of radiopharmaceuticals in imaging to drug discovery and targeted therapies. All these articles have been peer reviewed by members of editorial board including guest editors. Here, I would personally like to take this opportunity to thank everyone on the editorial board who has volunteered his/her time to review the various articles that we have received and also the editorial staff at Bentham Science. Current Radiopharmaceuticals has caught the interest of many scientists working in Nuclear Medicine. The journal owes its success to all the authors who have submitted high quality manuscripts sharing in-depth knowledge in the area of radiopharmaceuticals to produce thematic issues. The idea behind thematic ‘Hot Topic’ issues is to generate maximum impact factor for the published material in that particular subject area of radiopharmaceuticals and nuclear medicine. A new feature for 2014 submission of manuscripts to the journal will include a graphical abstract to summarize the contents of the article in a concise pictorial form, which will enable rapid viewing of the journals' contents and help capture the readers’ attention. The sixth volume of Current Radiopharmaceuticals contains articles on a wide range of hot topics. The efforts and determination of the editorial board and guest editors have helped promote the journal at various scientific meetings owing to its MEDLINE status since 2011. Our next goal is to earn soon an impact factor for the journal. In this ‘mission’, the help in diffusing our articles submitted by associate and guest editors, members of the editorial board, authors and interested readers will be of core importance. In this editorial review, I have summarized all the abstracts from 2013 issues 1 to 4. The first article of the year by Latli et al. is entitled as ‘Sodium-Proton Exchanger Isoform-1: Synthesis of a Potent Inhibitor Labeled with Deuterium and Carbon-14’, which gives an account of the synthesis of carbon-14 and deuterium labeled N-[4-(1- acetyl-piperidin-4-yl)-3-trifluoromethyl-benzoyl]-guanidine, a potent sodium-proton exchanger NHE-1 inhibitor. These NHEs are plasma membrane proteins that are essential in the regulation of intracellular pH of the myocardium and the labeled NHE-1 inhibitors have been used to evaluate ADME studies. The next article ‘Synthesis and Evaluation of 99mTc Chelate-conjugated Bevacizumab’ by Camacho et al. discusses the role of the monoclonal antibody bevacizumab as a possible imaging agent against vascular endothelial growth factor (VEGF) in various animal models. The modified imaging agent 99mTc-HYNIC-bevacizumab was evaluated using the adenocarcinoma animal model. The authors concluded that this SPECT imaging agent has potential in tumor imaging at the preclinical level. In the following article on ‘Biodistribution and Dosimetry of 177Lu-tetulomab, a New Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma’ by Repetto-Llamazares et al., the authors have evaluated the biodistribution of the following anti- CD37 radioimmunoconjugates177Lu-tetraxetan-tetulomab and 177Lu-tetraxetan-rituximab against free 177Lu. They used nude mice implanted with Daudi lymphoma xenografts and suggested that a higher tumor radiation dose can be reached using177Lutetraxetan- tetulomab in the clinic arena. In the article subjected as ‘Novel 99mTc-labeled Diphosphonic Acid as Potential Bone Seeking Agent: Synthesis and Biological Evaluation’ by Qiu et al., the authors have managed to prepare a novel zoledronate derivative, BIBDP labeled with 99mTc in high radiochemical purity with a good stability in vitro profile. This imaging agent showed a high specificity and efficacy in bone uptake compared to99mTc-MDP and 99mTc-ZL. The clear images were obtained after 1 h from using SPECT and this indicated that 99mTc- BIBDP has great potential for bone imaging. Subsequently, in the next article with the title ‘Peptide Imaging with Somatostatin Analogs: More than Cancer Probes’ by Cascini et al., the authors have studied the imaging of neuroendocrine tumors (NETs) using the diagnostic tool Somastostatin (SS) scintigraphy (SRS). NETs and a number of non-neoplastic cells have been shown to possess a high affinity for binding between SS and its receptors (sstr). Numerous SS analogs have been studied and the pentetreotide labeled with In-111 has been described the one most widely used for imaging due to its high affinity towards sstr 2 and 5. The development of these SPECT imaging agents will enable the detection of NET and other disease processes. Furthermore, the article ‘Bone Metastases Radiopharmaceuticals: An Overview’ by Cuccurullo et al. reviews a number of radiolabeled compounds that are successfully used to detect and/or characterize bone metastases. This approach uses two radionuclide functional techniques scintigraphy and positron emission tomography (PET) imaging. Therefore, the diagnosis and evaluation of skeletal metastases require a combined approach of different diagnostic methods using the appropriate radiopharmaceutical. The last article in issue 1 is by Peter Mitrasinovic entitled as, ‘Some Implications of Receptor Kinase Signaling Pathway for Development of Multi-targeted Kinase Inhibitors.’ In this article, the author evaluates the various radiolabeled agents for PET and SPECT imaging against the epidermal growth factor receptors (EGFRs), especially towards the next generation of multitargeted kinase inhibitors. Issue 2 begins with the article on ‘Radionuclide Antibody-Conjugates, a Targeted Therapy towards Cancer’ by Kitson et al. In this article, they have evaluated the use of monoclonal antibodies (mAbs), peptide conjugates and various chemical compounds to develop targeted therapies towards the treatment of oncological diseases. These TAT bio-vectors are able to transport a dose of alpha particles to destroy cancer cells. Radionuclide antibody-conjugates (RACs), labeled with beta emitters, have already been used in humans. The article concludes on the theory of tumor-antivascular- alpha-therapy (TAVAT) which may give rise to an alternative mechanism for TAT. This led to the article ‘Generator Breakthrough and Radionuclidic Purification in Automated Synthesis of 68Ga-DOTANOC’ by Belosi et al.; in this research, the authors have studied the efficacy of cationic pre-purification using commercial STRATAX- C, as well as distribution of the 68Ge contaminant during the synthesis of labeled peptides. The generator waste, STRATA-XC purification cartridge, synthesis waste and the final product were quantitatively analyzed by high resolution gamma ray spectrometry. They concluded that the synthesis using modular automated system produces 68Ga-DOTANOC, with limited user intervention. The 68Ge content in the final formulation was below 2x10-7% thus satisfying quality prerequisites for the radiopharmaceutical preparations. The next article is entitled as ‘Comparing High LET 227Th- and Low LET 177Lu-trastuzumab in Mice with HER-2 Positive SKBR-3 Xenografts’ by Abbas et al.; in this study, the authors set out to compare the biodistribution, normal tissue toxicity and therapeutic effect of the alpha-particle emitting 227Th-trastuzumab and the beta-particle emitting 177Lu-trastuzumab. These studies were carried out in mice with HER2- expressing SKBR-3 breast cancer xenografts. They concluded that thexenograft model gave a higher RBE for 227Th-trastuzumab compared to177Lu-trastuzumab, while the therapeutic index of 177Lutrastuzumab was superior to that of 227Th-trastuzumab. Then comes the article ‘[131I]IAZA as a Molecular Radiotherapeutic (MRT) Drug: Wash-Out with Cold IAZA Accelerates Clearance in a Murine Tumor Model’ by Mercer et al.; here the authors have demonstrated in animal models that a wash out procedure using [131I]IAZA as a Molecular Radiotherapeutic (MRT) drug could be utilized in the treatment of tumor hypoxia. The drawback to this approach was the high radioactivity level in the blood. Therefore to modulate the clearance of bound and free radioactive IAZA, non-radioactive (cold) IAZA was administered to the Balb/C EMT-6 murine tumor model. After 1 hour, an injection of high specific activity [125I][IAZA was administered in the Balb/C EMT-6 murine tumor model. This ‘wash out’ procedure reduced the concentrations of radioactivity by at least 40% in all tissues especially in the kidney and liver, and least at the tumor site. Next is the article entitled as ‘The Dilemma of Localizing Disease Relapse After Radical Treatment for Prostate Cancer: What is the Value of the Actual Imaging Techniques?’ by Schiavina et al.; this paper seeks to evaluate the management of patients with BCR after radical treatment of prostate cancer from the urologist point of view. They concluded that Multiparametric Magnetic Resonance Imaging may have a role in the early phase of PSA relapse. Conventional imaging, such as bone scan and CT, is not suggested in the initial phase of BCR. Recently, it has been reported that PET/CT allows changes to the therapeutic strategy (from palliative to curative treatment and vice-other biomolecules with theversa) in about 20% of cases. In recent years, the new radiotracer 18F-FACBC has been proposed as a possible alternative radiopharmaceutical to detect prostate cancer relapse. In the article entitled as ‘What is Currently the Best Radiopharmaceutical for the Hybrid PET/CT Detection of Recurrent Medullary Thyroid Carcinoma?’ by Slavikova et al., the authors have voyaged to review literature evidence about the efficacy and tolerance of radiopharmaceuticals towards three targets of PET/CT imaging (glucose metabolism, bio-amines metabolism and somatostatin receptors). They also included bone scintigraphy which was recommended in the Guidelines of European Society for Medical Oncology (ESMO). The concluding article of issue 2 comes with the title ‘Targeted Alpha Therapy with 227Th-trastuzumab of Intraperitoneal Ovarian Cancer in Nude Mice’ by Heyerdahl et al.; the aim of this current study is to investigate the therapeutic effect of 227Thradioimmunotherapy on intraperitoneally growing human bioluminescent HER2 positive ovarian cancer cells. They concluded that targeted alpha therapy using 227Th-trastuzumab towards human SKOV3-luc-D3 cells growing intraperitoneally in nude mice was clearly superior to unlabeled trastuzumab therapy. These results warrant further studies of 227Thradioimmunotherapy used as adjuvant treatment and for metastatic cancer. The leading article in issue 3 is entitled as ‘New Issues for Copper-64: from Precursor to Innovative Pet Tracers in Clinical Oncology’ by Evangelista et al.; in this paper, the authors have analyzed the potential applications for copper-64 as a PET imaging agent in the clinical oncology setting. Copper-64 has been reported to emit both positrons and β-particles and to be suitable for the labeling of numerous molecules that could be used for radionuclide imaging with applications in radionuclide therapy. Unfortunately, due to limited available data on radiotracers labeled with radio-copper and in particular on the use of 64CuCl2 in cancer patients further investigations are required. The second article on, ‘Gadolinium-Deferasirox-D-Glucosamine: Novel Anti-Tumor and MR Molecular (Theranostic) Imaging Agent’ by Amanlou et al. outlines the reason for their study to evaluate the imaging agent gadolinium-deferasirox-Dglucosamine. Thisnon-radioactive labeled glucose analog to image cancer tissue and heart function was carried out using MRI instead of PET imaging. This approach would circumvent the use of tracers such as 18FDG in making a diagnosis of cancer and therefore consideration must be given to this new MRI imaging agent. The third article on ‘Mixed Tridentate π-Donor and Monodentate π-Acceptor Ligands as Chelating Systems for Rhenium- 188 and Technetium-99m Nitrido Radiopharmaceuticals’ by Boschi et al. presents a new molecular metallic fragment for labeling biologically active molecules with 99mTc and 188Re. The system was composed of a combination of tridentate π-donor and monodentate π-acceptor ligands bound to a [M Ξ N]2+ group (M = 99mTc, 188Re) in a pseudo square-pyramidal geometry. The investigation was further extended to comprise a series of ligands formed by simple combinations of two basic amino acids or pseudo-amino acids to yield potential tridentate chelating systems having [S, N, S] and [N, N, S] with π-donor atoms. Labeling yields and in vitro stability were investigated using different ancillary ligands. The results showed that SNS-type ligands afforded the highest labeling yields and the most robust 3+1 nitrido complexes with both 99mTc and 188Re. Therefore, this new chelating system can be conveniently employed for labeling peptides and other biomolecules with the [M ΞN]2+ group. The following article entitled as ‘Cellular Toxicity and Apoptosis Studies in Osteocarcinoma Cells, a Comparison of 177Lu- EDTMP and Lu-EDTMP’ by Kumar et al. outlines a study regarding the cell uptake of 177Lu-EDTMP agent in osteocarcinoma cell lines to investigate the underlying mechanism of cellular toxicity. These studies indicate that the 177Lu-EDTMP binds to mineralized bone cells and induces apoptotic cell death in MG63 cells. Finally, the last article of issue 3 on ‘Targeted Radionuclide Therapy - An Overview’ by Dash et al.; discusses the use of Radionuclide therapy (RNT) based on the concept of delivering cytotoxic levels of radiation to diseased sites. The primary objective was to provide an overview on the role of radionuclide therapy in the treatment of different diseases such as polycythemia, thyroid malignancies, metastatic bone pain, radiation synovectomy, hepatocellular carcinoma (HCC), neuroendocrine tumors (NETs), non-Hodgkin’s lymphoma (NHL) and others. The article discusses many factors in choosing the appropriate radionuclide based on its availability, the type of emissions, linear energy transfer (LET), and physical half-life. Issue 4 starts with the article entitled as ‘Radiolabeled Peptides for Alzheimer’s Diagnostic Imaging: Mini Review’ by Barrios-Lopez et al.; in this paper, the authors have reviewed the use of molecular imaging tools to provide an in vivo visualization of Aβ plaques in the pathology of Alzheimer’s disease (AD). The specific identification of amyloid plaques would allow a more accurate prognosis and ensure more effective clinical trials of anti-amyloid agents at an earlier disease stage. The emphasis of this review was on the development of Aβ peptide radiopharmaceuticals. They also included nano-carriers based on Molecular Trojan horses or nano-particles for applications towards in vivo amyloid imaging in AD. Two of the priorities for the treatment of AD are the early detection and accurate chart progression of the accumulation of Aβ plaques in human brains. The next article ‘SPECT Radiopharmaceuticals for Dementia’ by Guidotti et al. discusses various imaging tools used to study neurodegenerative diseases with an emphasis on SPECT. The use of SPECT tracers was thought to be in decline compared to PET imaging in neurology. Today, a wide range of novel SPECT radiotracers, dual-SPECT tracer techniques and receptor targeting designed radiopharmaceuticals are currently being utilized for studying various disease processes. The development of new hybrid SPECT imaging systems integrated with other imaging modalities (e.g. MRI, CT, ultrasound techniques) has contributed to the improvement of the image resolution. Therefore, all of these improved conditions especially those towards neuroimaging bring renewed interest in the development of new SPECT radiopharmaceuticals towards clinical applications. The title ‘Risk Assessment and Economic Impact Analysis of the Implementation of New European Legislation on Radiopharmaceuticals in Italy: The Case of the New Monograph Chapter Compounding of Radiopharmaceuticals (PHARMEUROPA, Vol. 23, No. 4, October 2011)’ by Chitto et al. explains the Good Radiopharmaceuticals Practice (NBP) implementation which shows an extremely positive impact on risk management for both patients receiving Nuclear Medicine services and the healthcare organization. The implementation of the ministerial decree will allow for greater detectability of and control over a number of critical elements, paving the way for risk management and minimization. In the article ‘PET Radiotracers for Molecular Imaging in Dementia’, by Baskin et al., the authors review the current literature focusing on the PET radiotracers used for molecular imaging in dementia. The emphasis was on molecular imaging as a tool to collect relevant information to gain an overall accurate diagnosis, treatment and response monitoring towards dementia. The penultimate article on ‘Monoclonal Antibodies: Application in Radiopharmacy’ by Ligiero et al. reviews the data on the use of monoclonal antibodies in the last 40 years. All the data collected was summarized to reveal that this new class of medicine may bring great advance in the field of radiopharmacy, oncology and imaging. The final article of issue 4 entitled as ‘Thyroid Cancer Incidence 25 Years after Chernobyl, in a Romanian Cancer Center: Is it a Public Health Problem?’ by Piciu et al. discusses the increase of thyroid cancer (TC) throughout the world during the last decade. This may be due to more people being exposed to ionizing radiation. To investigate this further, the authors analyzed various patients’ records with TC who were treated at the Institute of Oncology Cluj-Napoca, Romania. They performed a comparative analysis of the database at intervals of 10, 20 and 25 years after the 1986 Chernobyl nuclear accident. From the analysis of the data, they found changes in histological profiles and tumor sizes. They implied that, in addition to nuclear fallout, highly sensitive thyroid diagnostic procedures were responsible for this increase in reported incidence. This appears to be driven by improved discovery of small (<1 cm) preclinical tumors. A further investigation of these observations is needed to address any public health concerns. Moreover, we have some very interesting articles and hot topic issues, which will be published in the forthcoming issues. Hot topics for 2014 include ‘Lutetium-177 Labeled Therapeutics: Emerging Importance For Cancer Treatment And Therapy Of Chronic Disease’; ‘Radiopharmaceuticals For The Diagnosis and Treatment of Cancer’ and ‘The Use Of Positron Emission Tomography In External Beam Therapy Dose Planning.’ The journal is gaining pace and so is its reputation amongst researchers in pharmaceutical (imaging) companies, institutions and universities; all of this will lead to the future success of Current Radiopharmaceuticals. Here we remember Dirk Roeda who passed away on July 19, 2013 and was an active editorial board member of Current Radiopharmaceuticals since 2010 having completed two thematic issues on [18F] Fluoride Radiochemistry with Micheal Kassiou and Frédéric Dolle.

In recent years, the SPECT/CT hybrid modality has led to a rapid development of imaging techniques in nuclear medicine, opening new perspectives for imaging staff and patients as well. However, while, the clinical role of positron emission tomography-computed tomography (PET-CT) is well consolidated, the diffusion and the consequent value of single-photon emission tomography-computed tomography (SPECT-CT) has yet to be weighed, Hence, there is a need for a careful analysis, comparing the "potential" benefits of the hybrid modality with the "established" ones of the standalone machine. The aim of this article is to analyze the impact of this hybrid tool on the diagnosis of diseases of the central nervous system, comparing strengths and weaknesses of both modalities through the use of SWOT analysis.

Objective: Patient dose of 177Lu-DOTA-TATE, used for providing radiotherapeutic treatment to the patients suffering from cancers of neuroendocrine origin, could be prepared at the hospital radiopharmacy either ‘in-situ’ or by using freezedried kits. The objective of the present work is to formulate and evaluate a single vial freeze-dried DOTA-TATE kit, which is capable of producing up to 7.4 GBq (200 mCi) dose of 177Lu-DOTA-TATE and to compare the two methodologies presently used for the preparation of the agent. Experimental: Freeze-dried DOTA-TATE kits, comprising a lyophilized mixture of DOTA-TATE, gentisic acid and ammonium acetate, were prepared and used for the formulation of patient doses of 177Lu-DOTA-TATE. The kits were subjected to detailed radiochemical evaluation and the shelf-life of the kits was determined. The pharmacokinetic behavior of the agent was studied in normal Wistar rats. These kits were utilized for treating the patients suffering from various types of neuroendocrine cancers. Results: The freeze-dried kits were used for the preparation of up to 7.4 GBq (200 mCi) therapeutic doses of 177Lu- DOTA-TATE with a radiochemical purity of >99% and were found to have sufficiently long shelf-life. Biological studies carried out in normal Wistar rats exhibited no significant accumulation of activity in any of the vital organs/tissue except in kidneys and non-accumulated activity showed major renal clearance. Clinical studies carried out in cancer patients exhibited accumulation of activity in the cancerous lesions and metastatic sites. Conclusion: The kit was useful for the convenient preparation of therapeutic dose of 177Lu-DOTA-TATE, suitable for human administration. The use of kit is expected to reduce the batch failure and radiation exposure to the working personnel.

Background: The association of PET/CT and tumor markers can be considered complementary, since any significant increases of tumor markers can indicate the presence of disease while PET/CT is able to detect and describe the tumor sites. In this retrospective, single-institution study, we determine the correlation between cancer antigen (CA) 15.3 value and qualitative and semi-quantitative PET/CT data in breast cancer (BC) patients. Methods: 193 BC patients (median age 61 yrs) already treated with primary treatment (surgery and others) were identified through institutional databases. All patients underwent PET/CT for increase in tumor markers, post-therapy evaluation, restaging and doubtful conventional imaging for disease relapse. The CA15.3 values before PET/CT scan were collected for all patients. Clinical outcome was defined as presence or absence of disease recurrence based on follow-up data (histological or imaging findings). CA15.3 quartile values and qualitative and semi-quantitative (maximum Standardized Uptake Value – SUVmax) PET/CT findings were compared with chi-square test and linear regression analysis. Results: The mean value of CA15.3 was significantly higher in patients with positive than negative PET/CT (67.51±120.92 vs. 25.54±17.54, p<0.005). PET/CT was positive in 107 (55%) and negative in 86 (45%) patients; CA15.3 value was considered abnormal (≥ 31 UI/mL) in 85 (44%) patients; 57 of them showed positive PET/CT while 28 a negative scan (67 vs. 33%, p<0.05). In all 193 patients, the disease recurrence was found in 71 (37%), whereas 122 (63%) were disease-free. The diagnostic accuracy of PET/CT in all 193 patients was 74%. Among patients with normal CA15.3 value (n=108), 50 showed positive PET/CT; 24 out of these latter 50 patients (48%) had recurrence of disease. The combination of the highest quartile of CA15.3 (value>45 UI/ml) and FDG PET/CT determined high sensitivity and accuracy (92% and 82%, respectively) but a low specificity (50%) for restaging BC patients. The highest specificity (~ 70%) was found when PET/CT and 2nd quartile of CA15.3 (value: 12.95-25) were associated. No correlation between CA15.3 values and SUVmax was found (p=0.489); whereas a trend in increase of the CA15.3 value and SUVmax in the presence of visceral and no-visceral site of disease (22.4±16.2, 64.9±108 and 6.4±4.2, 8.2±5.1, respectively) was identified. Conclusions: The value of CA15.3 and PET/CT findings are consistently complementary. About 25% of BC patients with a negative CA15.3 value had a positive PET/CT and disease relapse. SUVmax and CA15.3 values are not correlated.

The present report discusses about the most important roles of nuclear medicine related to the early detection of breast cancer. We summarily describe the established and emerging diagnostic techniques, their indications and clinical impact for planar and tomographic breast scintigraphy, positron emission tomography (PET)/computed tomography (CT) and positron emission mammography (PEM).

Positron emission tomography [PET] is a powerful nuclear clinical imaging technique used for the detection and treatment of central nervous system (CNS) disorders, cardiovascular diseases, and certain cancers. Due to the often short half-lives of the radiolabeled compounds employed, the availability of relevant tracers is severely limited. Through the use of microfluidic techniques many of the limitations of conventional synthesis of radiotracers are alleviated, paving the way for diverse families of compounds to be developed with defined targets for imaging. This review will survey syntheses of various radiotracers using new microfluidic techniques being developed.

The routine manufacture of most short-lived positron-emitting radiopharmaceuticals (PERs) involves conventional heating to accelerate the radiolabeling process. Nucleophilic radiofluorination reactions are generally slow at lower temperatures, and are accompanied by thermal decomposition of both precursor and product at higher temperatures. This necessitates HPLC purification and results in lower recovered radiochemical yields (rRCYs). [18F]FAZA, a PER for clinical imaging of focal tissue hypoxia, is routinely manufactured in-house in 3-12% rRCY using a Health Canada approved conventional heating procedure. The microwave-assisted (MW) radiosynthesis of [18F]FAZA is now reported. Methods: Manual (MRDS) and automated (ASU) reagent delivery systems coupled to a commercial MW unit were built in-house. The MW unit controlled power, irradiation time and monitored reaction temperature (Tmax control), while the acetylAZA tosylate precursor and QMA AccelTM cartridge eluent reagents (K2CO3, K2.2.2) were dispensed by the MRDS or ASU. The radiofluorination yields (RFYs) and the chemical and radiochemical TLC profiles of the post-labeling reaction mixtures were compared to those obtained using the conventional heating production method and to those reported for optimized literature methods. Results: MW RFYs for [18F]FAZA reached >76% (n=3) in 3 min. Post-labeling analysis of the MW-assisted reaction mixtures demonstrated cleaner UV and radiochemical TLC profiles than those obtained from conventional heating in routine production runs; the relatively clean MW reactions allowed rapid HPLC isolation of [18F]FAZA in overall rRCYs of 55±4%. Conclusions: In practical terms, the MW process provided only small gains in reaction time and RFY, but produced only a few secondary impurities, thereby improving the rRCY in comparison to conventional heating methods. These findings provide a rationale for adaptation of the MW-assisted method for the routine production of clinical [18F]FAZA.

Purpose: Both, the constant presence of apparent hypermetabolism of the vermis cerebelli compared to the cerebellar hemispheres in traumatic brain injury, and the presence of a good relationship between the intensity of this sign and the severity of the clinical conditions have been addressed in previous studies. Aim of the present paper is to evaluate the possible correlation between the intensity of the finding and the medium and long term outcome in a group of patients. Materials and Methods: A group of 105 patients consecutively admitted to the Brain Injury Rehabilitation Center of our Hospital between 2005 and 2012 was studied with a 18FDG-PET/CT study of the brain after head trauma; the metabolic activity of the cerebellar vermis was semiquantitatively assessed (vermis/cerebellum ratio, V/C). After that, all patients received systematic monitoring of their performance status via the timely administration of commonly used tests (DRS, LCF and GOS) during one whole year after the head trauma. The V/C parameter was compared with the evolution of performance abilities, as shown by the rating scales. Results: Statistical analysis showed a significant direct association between the V/C ratio and the DRS score at each time point (3 months: P<0.001; 6 months: P<0.001; 12 months: P<0.001) and significant inverse association with the LCF score (3 months: P<0.001; 6 months: P<0.001; 12 months: P<0.001) and the GOS score (3 months: P<0.001; 6 months: P<0.001; 12 months: P<0.001) at each time point. Moreover, patients with a V/C ratio ≥ 1 have a significantly greater probability to achieve a good functional outcome as defined by a DRS score ≥ 3 points, a LCF score ≥ 7 points and and a GOS score =5 points. Conclusions: In our group of patients, the V/C parameter has demonstrated to be a predictor of outcome. If validated by more extensive experiences, this approach could offer the possibility of performing a reliable prognostic evaluation in a notoriously “difficult” class of patients with an acceptable technique and economical effort.

The melanoma targeting peptides (Ala-triazol)Ac-Re(Arg11)CCMSH and N4-CO-Re(Arg11)CCMSH were radiolabeled with [99mTc(CO)3]+ and [99mTcO2]+, respectively, and examined for in vitro cell binding, in vivo biodistribution and imaging properties. The (Ala-triazol)Ac-Re(Arg11)CCMSH and N4-CO-Re(Arg11)CCMSH were synthesized as protected peptides on resin followed by rhenium cyclization with [(C6H5)3P]2ReOCl3 in DMF. The peptides were labeled with 99mTc and examined for radiochemical stability and melanoma cell binding. In vivo biodistribution and SPECT/CT imaging studies were performed in B16/F1 melanoma tumor bearing C57 mice. 99mTc(CO)3-(Ala-Triazol)Ac- Re(Arg11)CCMSH and 99mTcO2-N4-CO-Re(Arg11)CCMSH were stable and internalized in B16/F1 melanoma cells upon binding. In vivo biodistribution studies revealed that tumor uptake of 99mTc(CO)3-(Ala-Triazol)Ac-Re(Arg11)CCMSH was 6.08±1.06% ID/g and 7.05±1.48% ID/g at 2 h and 4 h post injection, respectively. Tumor uptake of 99mTcO2-N4-CORe(Arg11)CCMSH was 7.54±1.82% ID/g and 2.28±0.22% ID/g at 1 h and 2 h post injection, respectively. SPECT/CT imaging studies showed that tumor selective uptake of the radiolabeled peptides, which was confirmed by competitive blocking studies.

Dementia with Lewy bodies (DLB) is the second most common cause of degenerative dementia after Alzheimer’s disease (AD). To improve the diagnosis of DLB, the latest diagnostic criteria incorporate findings from neuroimaging studies including sympathetic innervation imaging with iodine-123-metaiodobenzylguanidine (MIBG). According to these criteria a decreased MIBG myocardial uptake is an important finding supporting a clinical diagnosis of DLB. In this review the state of art and future perspectives of sympathetic innervation imaging by using MIBG in the diagnosis of DLB are discussed.