Molecular Nuclear Medicine Research Articles

Molecular imaging of pancreatic ductal adenocarcinoma

AbstractPancreatic ductal adenocarcinoma (PDAC), a deadly cancer characterized by multiple molecular alterations, remains the most lethal cancer, with a 5‐year survival rate of about 3–15%. Early diagnosis and treatment monitoring are essential to improve patient survival. Traditional imaging methods can only provide structural information, but not biological processes. Nuclear medicine imaging combines the high sensitivity of radionuclides with high‐resolution structural imaging to visualize specific targets of PDAC for more accurate and reliable diagnosis and monitoring of therapeutic responses. In this review, we summarize the available literature regarding molecular nuclear medicine imaging in PDAC. We classify the probe targets into two categories, targeting tumor cell membranous and the tumor microenvironment, respectively. We summarize the latest evidence in this field and outline how these emerging strategies could potentially optimize clinical practice.

Is there a consensus between clinical practice guidelines for conventional and molecular nuclear medicine studies in parathyroid pathology?

Hyperparathyroidism is a common calcium metabolic disorder, characterized by the presence of high concentrations or inappropriately normal concentrations of parathyroid hormone (PTH) in the context of high calcium. Pharmacological and surgical management is available as treatment. The objective of diagnostic imaging is to determine the location of the causal lesion. For these purposes, non-invasive methods can be divided into anatomical or functional studies, with nuclear medicine studies being in the latter category. The objective of this review, is to establish the similarities and differences that exist in the clinical practice guidelines on conventional and molecular nuclear medicine studies in parathyroid disease.

Imaging Bacteria with Radiolabelled Probes: Is It Feasible?

Bacterial infections are the main cause of patient morbidity and mortality worldwide. Diagnosis can be difficult and delayed as well as the identification of the etiological pathogen, necessary for a tailored antibiotic therapy. Several non-invasive diagnostic procedures are available, all with pros and cons. Molecular nuclear medicine has highly contributed in this field by proposing several different radiopharmaceuticals (antimicrobial peptides, leukocytes, cytokines, antibiotics, sugars, etc.) but none proved to be highly specific for bacteria, although many agents in development look promising. Indeed, factors including the number and strain of bacteria, the infection site, and the host condition, may affect the specificity of the tested radiopharmaceuticals. At the Third European Congress on Infection/Inflammation Imaging, a round table discussion was dedicated to debate the pros and cons of different radiopharmaceuticals for imaging bacteria with the final goal to find a consensus on the most relevant research steps that should be fulfilled when testing a new probe, based on experience and cumulative published evidence.

Photonuclear production, chemistry, and in vitro evaluation of the theranostic radionuclide 47Sc

BackgroundIn molecular imaging and nuclear medicine, theranostic agents that integrate radionuclide pairs are successfully being used for individualized care, which has led to rapidly growing interest in their continued development. These compounds, which are radiolabeled with one radionuclide for imaging and a chemically identical or similar radionuclide for therapy, may improve patient-specific treatment and outcomes by matching the properties of different radionuclides with a targeting vector for a particular tumor type. One proposed theranostic radionuclide is scandium-47 (47Sc, T1/2 = 3.35 days), which can be used for targeted radiotherapy and may be paired with the positron emitting radionuclides, 43Sc (T1/2 = 3.89 h) and 44Sc (T1/2 = 3.97 h) for imaging. The aim of this study was to investigate the photonuclear production of 47Sc via the 48Ti(γ,p)47Sc reaction using an electron linear accelerator (eLINAC), separation and purification of 47Sc, the radiolabeling of somatostatin receptor-targeting peptide DOTATOC with 47Sc, and in vitro receptor-mediated binding of [47Sc]Sc-DOTATOC in AR42J somatostatin receptor subtype two (SSTR2) expressing rat pancreatic tumor cells.ResultsThe rate of 47Sc production in a stack of natural titanium foils (n = 39) was 8 × 107 Bq/mA·h (n = 3). Irradiated target foils were dissolved in 2.0 M H2SO4 under reflux. After dissolution, trivalent 47Sc ions were separated from natural Ti using AG MP-50 cation exchange resin. The recovered 47Sc was then purified using CHELEX 100 ion exchange resin. The average decay-corrected two-step 47Sc recovery (n = 9) was (77 ± 7)%. A radiolabeling yield of > 99.9% of [47Sc]Sc-DOTATOC (0.384 mg in 0.3 mL) was achieved using 1.7 MBq of 47Sc. Blocking studies using Octreotide illustrated receptor-mediated uptake of [47Sc]Sc-DOTATOC in AR42J cells.Conclusions47Sc can be produced via the 48Ti(γ,p)47Sc reaction and separated from natural Ti targets with a yield and radiochemical purity suitable for radiolabeling of peptides for in vitro studies. The data in this work supports the potential use of eLINACs for studies of photonuclear production of medical radionuclides and the future development of high-intensity eLINAC facilities capable of producing relevant quantities of carrier-free radionuclides currently inaccessible via routine production pathways or limited due to costly enriched targets.

Immuno-Imaging to Predict Treatment Response in Infection, Inflammation and Oncology.

Background: Molecular nuclear medicine plays a pivotal role for diagnosis in a preclinical phase, in genetically susceptible patients, for radio-guided surgery, for disease relapse evaluation, and for therapy decision-making and follow-up. This is possible thanks to the development of new radiopharmaceuticals to target specific biomarkers of infection, inflammation and tumour immunology. Methods: In this review, we describe the use of specific radiopharmaceuticals for infectious and inflammatory diseases with the aim of fast and accurate diagnosis and treatment follow-up. Furthermore, we focus on specific oncological indications with an emphasis on tumour immunology and visualizing the tumour environment. Results: Molecular nuclear medicine imaging techniques get a foothold in the diagnosis of a variety of infectious and inflammatory diseases, such as bacterial and fungal infections, rheumatoid arthritis, and large vessel vasculitis, but also for treatment response in cancer immunotherapy. Conclusion: Several specific radiopharmaceuticals can be used to improve diagnosis and staging, but also for therapy decision-making and follow-up in infectious, inflammatory and oncological diseases where immune cells are involved. The identification of these cell subpopulations by nuclear medicine techniques would provide personalized medicine for these patients, avoiding side effects and improving therapeutic approaches.

Identification of Radioactive Iodine Refractory Differentiated Thyroid Cancer.

Most differentiated thyroid cancer (DTC) patients have an excellent prognosis. However, about one-third of DTC patients with recurrent or metastatic disease lose the hallmark of specific iodine uptake initially or gradually and acquire radioactive iodine-refractory DTC (RAIR-DTC) with poor prognosis. Due to the potentially severe complications from unnecessarily repeated RAI therapy and encouraging progress of multiple targeted drugs for advanced RAIR-DTC patients, it has become crucial to identify RAIR-DTC early. In this review, we focus on the progress and controversies regarding the defining of RAIR-DTC, further with subsistent approaches and promising molecular nuclear medicine imaging in identifying RAIR-DTC, which may shed light on the proper management methodsof such patients.

SPECT and PET imaging in Alzheimer’s disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Beta-amyloid (Aβ) deposition and neurofibrillary tangles (NFTs) of abnormal hyperphosphorylated tau protein are the pathological hallmarks of the disease, accompanied by other pathological processes such as microglia activation. Functional and molecular nuclear medicine imaging with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) techniques provides valuable information about the underlying pathological processes, many years before the appearance of clinical symptoms. Nuclear neuroimaging in AD has made great progress in the past two decades and has extended beyond the traditional role of brain perfusion and glucose metabolism evaluation. Intense efforts in radiopharmaceuticals research have led to the development of various probes able to detect Aβ deposits, tau protein accumulation, microglia activation and neuroinflammation. As a result, SPECT and PET have proposed to serve as biomarkers in recently revised diagnostic clinical criteria for the early diagnosis of AD and the prediction of progression to AD in mild cognitive impairment (MCI) subjects.

Bioluminescence imaging of a tumor-selective, thymidine kinase-defective vaccinia virus Guang9 strain after intratumoral or intraperitoneal administration in mice.

Vaccinia virus has been used as an oncolytic virus because of its capacity to preferentially infect tumors rather than normal tissues. The vaccinia Tian Tan strain, used as a vaccine against smallpox for millions of people in China, is a promising candidate for cancer therapy. In this study, we constructed an attenuated Tian Tan strain of Guang9 with a disrupted thymidine kinase gene to enhance tumor selectivity and an inserted firefly luciferase to monitor the viral distribution by in vivo bioluminescence imaging. Living animal imaging confirmed the high specificity of vaccinia Guang9 for tumor targeting after intratumoral and intraperitoneal administration. In addition, the vaccinia Guang9 strain produced higher in vivo luciferase activity and endured longer in immunocompromised nude mice than in immunocompetent C57BL/6 mice, all of which had been tumor-challenged. The luciferase activity and viral titers in excised tissues confirmed these conclusions. These data provide evidence for the safety and efficacy of the clinical application of vaccinia virus, which would be a promising approach for cancer therapy.

The role of theragnostics in oncology: an interview with Stefano Buono

Stefano Buono* speaks to Commissioning Editor, Sebastian Dennis-Beron: Stefano Buono is the Chief Executive Officer, a member of the board of directors, and a founder of Advanced Accelerator Applications (AAA). He has been responsible for overseeing AAA operations, including the development and commercialization of the current portfolio of diagnostic and therapeutic molecular nuclear medicine products, and listing AAA on Nasdaq (stock symbol: AAAP). Prior to founding the company in 2002, he worked as a physicist at the Centre for Advanced Studies, Research and Development, or CRS4, in Italy. During his 6-year tenure with CRS4, he headed a team of engineers working on different international research projects in the field of energy production and nuclear waste transmutation. Before working at CRS4, and alongside his appointment at CRS4, he worked with Physics Nobel Laureate Carlo Rubbia at The European Organization for Nuclear Research (CERN), the world’s largest research laboratory for particle physics, in Geneva, Switzerland. He actively participated in the development of CERN’s Adiabatic Resonance Crossing (ARC) method. He is the author of numerous scientific papers. He received his Master’s degree in Physics from the University of Turin, in Italy, in 1991.

Evaluation of diabetic foot infection in nuclear medicine.

Diabetic foot infection is not only the most common cause of hospitalization among diabetic patients, but is also associated with high morbidity, mortality and major utilization of the resources. Managing diabetic patients with suspected foot infection is highly dependent on an early and accurate determination of its presence and location. Medical imaging is often used in the workup of these patients, as clinical diagnosis of osteomyelitis is often difficult, and invasive bone biopsy is infrequently used due to many limitations. In this article, we review the role and accuracy of commonly used medical imaging modalities in the evaluation of diabetic patients with suspected foot infection including osteomyelitis with particular emphasis on molecular nuclear medicine imaging. The impact of imaging on patients' management is also discussed. We finally comment on possible future directions in hybrid molecular imaging techniques.

Oncolytic efficacy of thymidine kinase-deleted vaccinia virus strain Guang9.

Oncolytic virotherapy is being developed as a promising platform for cancer therapy due to its ability to lyse cancer cells in a tumor-specific manner. Vaccinia virus has been used as a live vaccine in the smallpox eradication program and now is being potential in cancer therapy with a great safety profile. Vaccinia strain Guang9 (VG9) is an attenuated Chinese vaccinia virus and its oncolytic efficacy has been evaluated in our previous study. To improve the tumor selectivity and oncolytic efficacy, we here developed a thymidine kinase (TK)-deleted vaccinia virus based on Guang9 strain. The viral replication, marker gene expression and cytotoxicity in various cell lines were evaluated; antitumor effects in vivo were assessed in multiple tumor models. In vitro, the TK-deleted vaccinia virus replicated rapidly, but the cytotoxicity varied in different cell lines. It was notably attenuated in normal cells and resting cells in vitro, while tumor-selectively replicated in vivo. Significant antitumor effects were observed both in murine melanoma tumor model and human hepatoma tumor model. It significantly inhibited the growth of subcutaneously implanted tumors and prolonged the survival of tumor-bearing mice. Collectively, TK-deleted vaccinia strain Guang9 is a promising constructive virus vector for tumor-directed gene therapy and will be a potential therapeutic strategy in cancer treatment.

Stress-induced molecules MICA as potential target for radioimmunotherapy of cancer

Improving the treatment of cancer, increasing their effectiveness and safety is the main objective in the medicine. Molecular nuclear medicine plays an important role in the therapy of cancer. Radioimmunotherapy (RIT) involves the use of antibodies conjugated with therapeutic radionuclides. More often for RIT use the radiolabeled monoclonal antibodies against tumor-associated antigens. Encouraging results have been achieved with this technology in the management of hematologic malignancies. On the contrary, solid tumors have been less responsive. Despite these encouraging results, new potential target for radioimmunodetection and RIT should be found. It was found to increase the level of tumor-associated molecules MICA in the serum of cancer patients. Use of anti-MICA monoclonal antibodies capable a specifically attach to cancer cell via NKG2D ligands and destroy it, is a very promising direction, both therapeutic and diagnostic standpoint.

Effects of PQQ on cognitive function induced by MK801 and its molecular imaging evaluation

International Journal of Developmental NeuroscienceVolume 47, Issue Part_A p. 26-26 Article ISDN2014_0096: Effects of PQQ on cognitive function induced by MK801 and its molecular imaging evaluation X.Q. Zhou, Corresponding Author X.Q. Zhou zhouxingqin@jsinm.org Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, ChinaE-mail address: zhouxingqin@jsinm.org (X.Q. Zhou).Search for more papers by this authorQ.C. Chen, Q.C. Chen Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, ChinaSearch for more papers by this authorS.S. Mao, S.S. Mao Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, ChinaSearch for more papers by this authorX.F. Qin, X.F. Qin Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, ChinaSearch for more papers by this authorX.J. Xu, X.J. Xu Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, ChinaSearch for more papers by this authorY.Y. Kong, Y.Y. Kong Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, ChinaSearch for more papers by this author X.Q. Zhou, Corresponding Author X.Q. Zhou zhouxingqin@jsinm.org Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, ChinaE-mail address: zhouxingqin@jsinm.org (X.Q. Zhou).Search for more papers by this authorQ.C. Chen, Q.C. Chen Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, ChinaSearch for more papers by this authorS.S. Mao, S.S. Mao Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, ChinaSearch for more papers by this authorX.F. Qin, X.F. Qin Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, ChinaSearch for more papers by this authorX.J. Xu, X.J. Xu Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, ChinaSearch for more papers by this authorY.Y. Kong, Y.Y. Kong Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, ChinaSearch for more papers by this author First published: 05 November 2015 https://doi.org/10.1016/j.ijdevneu.2015.04.078Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume47, IssuePart_AISDN 2014 AbstractsDecember 2015Pages 26-26 RelatedInformation

Internal radiation therapy: a neglected aspect of nuclear medicine in the molecular era.

With increasing evidence, internal radiation therapy, also known as brachytherapy, has become a neglected aspect of nuclear medicine in the molecular era. In this paper, recent developments regarding internal radiation therapy, including developments in radioiodine-131 (131I) and thyroid, radioimmunotherapy (RIT) for non-Hodgkin lymphoma (NHL), and radiopharmaceuticals for bone metastases. Relevant differences and status of their applications in China were mentioned as well. These molecular mediated internal radiation therapies are gaining increasing importance by providing palliative and curative treatments for an increasing number of diseases and becoming one of the important parts of molecular nuclear medicine.

Novel tumor-targeting, self-assembling peptide nanofiber as a carrier for effective curcumin delivery

The poor aqueous solubility and low bioavailability of curcumin restrict its clinical application for cancer treatment. In this study, a novel tumor-targeting nanofiber carrier was developed to improve the solubility and tumor-targeting ability of curcumin using a self-assembled Nap-GFFYG-RGD peptide. The morphologies of the peptide nanofiber and the curcumin-encapsulated nanofiber were visualized by transmission electron microscopy. The tumor-targeting activity of the curcumin-encapsulated Nap-GFFYG-RGD peptide nanofiber (f-RGD-Cur) was studied in vitro and in vivo, using Nap-GFFYG-RGE peptide nanofiber (f-RGE-Cur) as the control. Curcumin was encapsulated into the peptide nanofiber, which had a diameter of approximately 10–20 nm. Curcumin showed sustained-release behavior from the nanofibers in vitro. f-RGD-Cur showed much higher cellular uptake in αvβ3 integrin-positive HepG2 liver carcinoma cells than did non-targeted f-RGE-Cur, thereby leading to significantly higher cytotoxicity. Ex vivo studies further demonstrated that curcumin could accumulate markedly in mouse tumors after administration of f-RGD-Cur via the tail vein. These results indicate that Nap-GFFYG-RGD peptide self-assembled nanofibers are a promising hydrophobic drug delivery system for targeted treatment of cancer.

The importance of standardized interpretation of molecular breast imaging with dedicated gamma cameras

Breast cancer (BC) is the most common malignancy and the second leading cause of cancer death in females, accounting in the USA for 29% of the total new cancer cases and 14% of the total cancer deaths in 2012 [1]. Early diagnosis and treatment are of the utmost importance to improve prognosis. For detection and characterization of primary breast lesions, anatomical imaging including mammography, ultrasonography, and MRI are commonly employed. Scintimammography is a molecular nuclear medicine technique for breast imaging which uses single-photon radiopharmaceuticals such as Tc sestamibi and Tc tetrofosmin. It is a functional imaging modality so some of the main drawbacks of mammography are resolved [2]. It was developed almost 20 years ago with standard large field-of-view (FOV) gamma cameras. Certainly, the principal limiting factor in the clinical acceptance of scintimammography has been its low sensitivity for cancers of ≤1 cm in size, mainly because of the lack of suitable equipment specifically designed for breast imaging. Dedicated gamma cameras specifically built for breast imaging are now available. The use of these breast-optimized, small FOV, high-resolution cameras allows both greater flexibility in patient positioning (improving breast imaging by limiting the FOV and reducing image contamination from other organs, i.e. liver and heart) and breast compression, with an important increase in the target-to-background ratio [3]. In fact, the detector can be placed directly against the chest and a mild compression is possible, to reduce breast thickness and improve the camera’s sensitivity. Moreover, by design, these specific cameras are also able to provide better intrinsic and extrinsic spatial resolution than standard ones, with an enhancement in contrast resolution for small lesions [4], and to acquire projections similar to those of mammography (craniocaudal, mediolateral oblique and true lateral). Studies comparing standard and breast-specific cameras have provided clinical evidence that the dedicated ones show better accuracy in molecular breast imaging, especially in increasing the sensitivity for subcentimetre lesions [4–6]. It is worth noting that a recent retrospective review of one institution’s experience with breast-specific gamma imaging (BSGI) has indicated that this test is not only both sensitive (93%) and specific (79%) for the identification of BC, but it is also helpful as an adjunct to standard breast imaging modalities for problem solving in indeterminate cases [7]. Moreover, in this study including 416 cases, BSGI was demonstrated to be useful in evaluating lesions difficult to biopsy and in patients who desired further testing rather than biopsy or short term follow-up of their breast abnormality. These interesting data have been then confirmed in a multicentre clinical patient registry analysis, which aimed to quantify the impact of BSGI on the management of patients with BC in clinical practice, and to identify the subgroups benefiting more from the use of this examination [8]. A total of 1,042 patients were evaluated. All of them had at least one (the majority two or more) of the following indications: equivocal mammography or ultrasonography findings; a personal history of BC; a family history or other factors establishing a high risk of developing BC; a recent positive mammogram; clinical findings such as a palpable mass, breast pain or bloody nipple discharge; dense breast O. Schillaci (*) Department of Biopathology and Diagnostic Imaging, University “Tor Vergata”, Viale Mazzini 121, 00195 Rome, Italy e-mail: orazio.schillaci@uniroma2.it

SPECT and PET Imaging of Meningiomas

Meningiomas arise from the meningothelial cells of the arachnoid membranes. They are the most common primary intracranial neoplasms and represent about 20% of all intracranial tumors. They are usually diagnosed after the third decade of life and they are more frequent in women than in men. According to the World Health Organization (WHO) criteria, meningiomas can be classified into grade I meningiomas, which are benign, grade II (atypical) and grade III (anaplastic) meningiomas, which have a much more aggressive clinical behaviour. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are routinely used in the diagnostic workup of patients with meningiomas. Molecular Nuclear Medicine Imaging with Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) could provide complementary information to CT and MRI. Various SPECT and PET tracers may provide information about cellular processes and biological characteristics of meningiomas. Therefore, SPECT and PET imaging could be used for the preoperative noninvasive diagnosis and differential diagnosis of meningiomas, prediction of tumor grade and tumor recurrence, response to treatment, target volume delineation for radiation therapy planning, and distinction between residual or recurrent tumour from scar tissue.

Funktionelle und molekulare Bildgebung bei Brusttumoren

Molecular imaging is concerned with the presentation, description and quantification of biological and physiological processes at the cellular and molecular level. Most recently molecular imaging has started to become established in breast diagnostics. This review article will give an overview of procedures which are either in the preclinical development stage or which have already become clinically established. Molecular nuclear medicine breast imaging (breast-specific gamma imaging [BSGI] and positron emission mammography [PEM]) together with specific radiotracers and contrast media will be discussed. The possibilities for magnetic resonance imaging in functional (DWI) and metabolic (MRSI) imaging of breast lesions and the combined application of nuclear medicine and magnetic resonance imaging (PET/MRI) will be explained. Furthermore, an overview on the preclinical procedure and the possible clinical applications of optical and photoacoustic imaging will be given.

Synthesis, Characterization and Quantum Chemical Studies on a Novel Cobalt(II) 1,2,3,4-Tetra-(4-pyridyl)-thiophene Coordination Polymer

†Key Laboratory of Nuclear Medicine, Ministry of Health & Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, P. R. China. *E-mail: qiulingwx@gmail.com Coordination Chemistry Institute, State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, P. R. China Received November 27, 2009, Accepted November 27, 2009

Use of isotopes in the diagnosis of hematopoietic disorders

Isotopes of iron have been paramount in clinical tracer studies of hematopoiesis. Kinetics of disappearance from plasma, appearance in circulating erythrocytes, and localization in general areas of bone marrow, spleen, and liver were early revealed by gamma-/beta-emitting Fe-59 with note of characteristic differences of kind and degree of dysfunction among various anemias. Findings have helped in management (e.g., decisions about splenectomy). Positron/gamma-emitting Fe-52 (better for imaging) has provided more detail on marrow expansion and erythropoietic relocation. Other gamma-emitting tracers of hematopoiesis have been In-111 (linked to transferrin) and technetium 99m (Tc-99m) colloids (localizing to reticuloendothelial cells, which have close association with blood cell progenitors), but Fe-52 has proved to be more accurate for recognition of erythropoiesis. Occasional diverse heterotopic sites of hematopoiesis beyond spleen and liver in states of bone marrow disease have posed diagnostic challenges and also raised questions about migration and/or activation of stem cells. Studies of granulopoiesis utilize Tc-99m--labeled leukocytes or Tc99m-labeled antibodies to circulating and progenitor white cells. Iron-deficiency anemias due to malnutrition, malabsorption, blood loss, or special need are explored by dual study (oral vs intravenous) with radioactive (Fe-59, Fe-55) or stable (Fe-54, Fe-57) iron isotopes, which can guide dietary supplementation. Tests for B-12 deficiency in pernicious anemia or malabsorption with radioisotopes of cobalt (Co-57, Co-58) have been upgraded in sensitivity and scope. Rates of oxidation to expired carbon dioxide from particular carbon (radioactive C-14 or stable C-13)--labeled compounds can test B-12 or folic acid deficiencies or gastric infestation as causes of megaloblastic anemias.