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Radiopharmaceuticals used for in vivo imaging of inflammatory conditions can be conveniently classified into six categories according to the different phases in which the inflammatory process develops. The trigger of an inflammatory process is a pathogenic insult (phase I) that causes activation of endothelial cells (phase II); there is then an increase of vascular permeability followed by tissue oedema (phase III). Phase IV is characterised by infiltration of polymorphonuclear cells, and a self-limiting regulatory process called apoptosis is observed (phase V). If the inflammatory process persists, late chronic inflammation takes place (phase VI). In some pathological conditions, such as organ-specific autoimmune diseases, chronic inflammation is present early in the disease. The aim of nuclear medicine in the field of inflammation/infection is to develop noninvasive tools for the in vivo detection of specific cells and tissues. This would allow early diagnosis of initial pathophysiological changes that are undetectable by clinical examination or by other diagnostic tools, and could also be used to evaluate the state of activity of the disease during therapy. These potential applications are of great interest in clinical practice. In this review, we describe the various approaches that have been developed in the last 25 years of experience. Recent advances in the diagnosis of inflammatory processes have led to the development of specific radiopharmaceuticals that are intended to allow specific stage-related diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: To discriminate between post-treatment changes and tumor recurrence in patients affected by glioma undergoing surgery and chemoradiation with a new enhancing lesion is challenging. We aimed to evaluate the role of ASL, DSC, DCE perfusion MRI, and 18F-DOPA PET/CT in distinguishing tumor recurrence from post-treatment changes in patients with glioma., Materials and Methods: We prospectively enrolled patients with treated glioma (surgery plus chemoradiation) and a new enhancing lesion doubtful for recurrence or post-treatment changes. Each patient underwent a 1.5T MRI examination, including ASL, DSC, and DCE PWI, and an 18 F-DOPA PET/CT examination. For each lesion, we measured ASL-derived CBF and normalized CBF, DSC-derived rCBV, DCE-derived Ktrans, Vp, Ve, Kep, and PET/CT-derived SUV maximum. Clinical and radiological follow-up determined the diagnosis of tumor recurrence or post-treatment changes., Results: We evaluated 29 lesions (5 low-grade gliomas and 24 high-grade gliomas); 14 were malignancies, and 15 were post-treatment changes. CBF ASL, nCBF ASL, rCBV DSC, and PET SUVmax were associated with tumor recurrence from post-treatment changes in patients with glioma through an univariable logistic regression. Whereas the multivariable logistic regression results showed only nCBF ASL (p = 0.008) was associated with tumor recurrence from post-treatment changes in patients with glioma with OR = 22.85, CI95%: (2.28-228.77)., Conclusion: In our study, ASL was the best technique, among the other two MRI PWI and the 18F-DOPA PET/CT PET, in distinguishing disease recurrence from post-treatment changes in treated glioma., (© 2024. The Author(s).)

Introduction: Thyroidectomy followed by radioactive iodine therapy (RAI) is the treatment of choice for differentiated thyroid carcinoma (DTC). Serum thyroglobulin (Tg) measurement has proved to be useful for predicting persistent and/or recurrent disease during follow-up of DTC patients. In our study, we evaluated the risk of disease recurrence in patients with papillary thyroid carcinoma (PTC), who were treated with thyroidectomy and RAI, by measuring serum Tg at different time-points: at least 40 days after surgery, in euthyroidism with TSH < 1.5 and usually 30 days before RAI (Tg -30 ), on the day of RAI (Tg 0 ), and seven days after RAI (Tg +7 )., Methods: One hundred and twenty-nine patients with PTC were enrolled in this retrospective study. All patients were treated with 131 I for thyroid remnant ablation. Disease relapse (nodal disease or distant disease) during at least 36 months follow-up was evaluated by serum measurements of Tg, TSH, AbTg at different time points and by imaging techniques (neck ultrasonography, 131 I-whole body scan (WBS) after Thyrogen ® stimulation). Typically, patients were assessed at 3, 6, 12, 18, 24, and 36 months after RAI. We classified patients in five groups: (i) those who developed nodal disease (ND), (ii) those who developed distant disease (DD), (iii) those with biochemical indeterminate response and minimal residual thyroid tissue (R), (iv) those with no evidence of structural or biochemical disease + intermediate ATA risk (NED-I), and (v) those with no evidence of structural or biochemical disease + low ATA risk (NED-L). ROC curves for Tg were generated to find potential discriminating cutoffs of Tg values in all patients' groups., Results: A total of 15 out of 129 patients (11.63%) developed nodal disease and 5 (3.88%) distant metastases, during the follow-up. We found that Tg -30 (with suppressed TSH) has the same sensitivity and specificity than Tg 0 (with stimulated TSH), and it is slightly better than Tg +7 , which can be influenced by the size of the residual thyroid tissue., Conclusion: Serum Tg -30 value, measured in euthyroidism 30 days before RAI, is a reliable prognostic factor to predict future nodal or distant disease, thus allowing to plan the most appropriate therapy and follow-up.

Immune system is emerging as a crucial protagonist in a huge variety of oncologic and non-oncologic conditions including response to vaccines and viral infections (such as SARS-CoV-2). The increasing knowledge of molecular biology underlying these diseases allowed the identification of specific targets and the possibility to use tailored therapies against them. Immunotherapies and vaccines are, indeed, more and more used nowadays for treating infections, cancer and autoimmune diseases and, therefore, there is the need to identify, quantify and monitor immune cell trafficking before and after treatment. This approach will provide crucial information for therapy decision-making. Imaging of B and T-lymphocytes trafficking by using tailored radiopharmaceuticals proved to be a successful nuclear medicine tool. In this review, we will provide an overview of the state of art and future trends for "in vivo" imaging of lymphocyte trafficking and homing by mean of specific receptor-tailored radiopharmaceuticals., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Copper is required for cancer cell proliferation and tumor angiogenesis. Copper-64 radionuclide ( 64 Cu), a form of copper chloride ( 64 CuCl 2 ), is rapidly emerging as a diagnostic PET/CT tracer in oncology. It may also represent an interesting alternative to gallium-68 ( 68 Ga) as a radionuclide precursor for labelling radiopharmaceuticals used to investigate neuroendocrine tumors and prostate cancer. This emerging interest is also related to the nuclear properties of 64 CuCl 2 that make it an ideal theragnostic nuclide. Indeed, 64 CuCl 2 emits β + and β - particles together with high-linear-energy-transfer Auger electrons, suggesting the therapeutic potential of 64 CuCl 2 for the radionuclide cancer therapy of copper-avid tumors. Recently, 64 CuCl 2 was successfully used to image prostate cancer, bladder cancer, glioblastoma multiforme (GBM), and non-small cell lung carcinoma in humans. Copper cancer uptake was related to the expression of human copper transport 1 (hCTR1) on the cancer cell surface. Biodistribution, toxicology and radiation safety studies showed its radiation and toxicology safety. Based on the findings from the preclinical research studies, 64 CuCl 2 PET/CT also holds potential for the diagnostic imaging of human hepatocellular carcinoma (HCC), malignant melanoma, and the detection of the intracranial metastasis of copper-avid tumors based on the low physiological background of radioactive copper uptake in the brain.

Background: Dissociative disorders encompass loss of integration in essential functions such as memory, consciousness, perception, motor control, and identity. Nevertheless, neuroimaging studies, albeit scarce, have suggested the existence of particular brain activation patterns in patients belonging to this diagnostic category. The aim of this review is to identify the main functional neuroimaging correlates of dissociative disorders., Methods: we searched the PubMed database to identify functional neuroimaging studies conducted on subjects with a diagnosis of a dissociative disorder, following the PRISMA guidelines. In the end, we included 13 studies in this systematic review, conducted on 51 patients with dissociative identity disorder (DID), 28 subjects affected by depersonalization disorder, 24 with dissociative amnesia, and 6 with other or not specified dissociative disorders., Results: Prefrontal cortex dysfunction seems prominent. In addition, changes in the functional neural network of the caudate are related to alterations of identity state and maintenance of an altered mental status in DID. Another role in DID seems to be played by a dysfunction of the anterior cingulate gyrus. Other regions, including parietal, temporal, and insular cortices, and subcortical areas were reported to be dysfunctional in dissociative disorders., Conclusions: Prefrontal dysfunction is frequently reported in dissociative disorders. Functional changes in other cortical and subcortical areas can be correlated with these diagnoses. Further studies are needed to clarify the neurofunctional correlations of each dissociative disorder in affected patients, in order to identify better tailored treatments., Competing Interests: The authors declare no conflict of interest.

Introduction: Nuclear medicine plays a crucial role for personalized therapy, mainly in oncology. Chemotherapy and radiotherapy present some disadvantages and research is shifting toward nanotechnology with significant improvements in therapy and diagnosis of several cancers. Indeed, nanoparticles can be tagged with different radioisotopes for single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging and for therapy. This review describes the current state of the art of 64 Copper-labeled nanoparticles for PET imaging of cancer., Evidence Acquisition: We performed a systematic analysis of literature using the terms "64CuCl2," "64Cu," "Copper" AND "nanoparticle" AND "PET" in online databases: i.e. PubMed/MEDLINE and Scopus. The search was limited to English papers and original articles. We excluded articles not in English language, abstracts, case reports, review articles and meeting presentations., Evidence Synthesis: Amongst the 116 articles retrieved, 88 were excluded because reviews, or not in English, or only in-vitro studies or meeting presentations. We considered only 28 original papers. The most used nanoparticles are liposomes and they are mainly used in breast cancer although other animal models of cancer have been also investigated., Conclusions: The results showed that nanoparticles can be considered a promising radiopharmaceutical for PET imaging of different type of cancer.

Poly-lactic-co-glycolic acid nanoparticles (PLGA-NPs) were approved by the Food and Drug Administration (FDA) for drug delivery in cancer. The enhanced permeability and retention (EPR) effect drives their accumulation minimizing the side effects of chemotherapeutics. Our aim was to develop a new theranostic tool for cancer diagnosis and therapy based on PLGA-NPs and to evaluate the added value of vascular endothelial growth factor (VEGF) for enhanced tumor targeting. In vitro and in vivo properties of PLGA-NPs were tested and compared with VEGF-PLGA-NPs. Dynamic light scattering (DLS) was performed to evaluate the particle size, polydispersity index (PDI), and zeta potential of both preparations. Spectroscopy was used to confirm the absorption spectra in the near-infrared (NIR). In vivo, in BALB/c mice bearing a syngeneic tumor in the right thigh, intravenously injected PLGA-NPs showed a high target-to-muscle ratio (4.2 T/M at 24 h post-injection) that increased over time, with a maximum uptake at 72 h and a retention of the NPs up to 240 h. VEGF-PLGA-NPs accumulated in tumors 1.75 times more than PLGA-NPs with a tumor-to-muscle ratio of 7.90 ± 1.61 (versus 4.49 ± 0.54 of PLGA-NPs). Our study highlights the tumor-targeting potential of PLGA-NPs for diagnostic and therapeutic applications. Such NPs can be conjugated with proteins such as VEGF to increase accumulation in tumor lesions.

Introduction: Paraganglioma (PGL) is a rare neuroendocrine tumor. Currently, the malignancy is defined as the presence of metastatic spread at presentation or during follow-up. Several gene mutations are listed in the pathogenesis of PGL, among which succinate dehydrogenase (SDHX), particularly the SDHB isoform, is the main gene involved in malignancy. A 55-year-old male without evidence of catecholamine secretion had surgery for PGL of the urinary bladder. After 1 year, he showed a relapse of disease and demonstrated malignant PGL without evidence of catecholamine secretion with a germline heterozygous mutation of succinate dehydrogenase B (SDHB). After failure of a second surgery for relapse, he started medical treatment with sunitinib daily but discontinued due to serious side effects. Cyclophosphamide, vincristine, and dacarbazine (CVD) chemotherapeutic regimen stopped the disease progression for 7 months., Conclusion: Malignant PGL is a very rare tumor, and SDHB mutations must be always considered in molecular diagnosis because they represent a critical event in the progression of the oncological disease. Currently, there are few therapeutic protocols, and it is often difficult, as this case demonstrates, to decide on a treatment option according to a reasoned set of choices.

Objective: Pancreatic scintigraphy with interleukin-2 radiolabeled with (99m)Tc ((99m)Tc-IL-2) is a technique used to image chronic inflammatory-mediated disorders. We used this method to detect a signal consistent with the presence of insulitis in patients with autoimmune diabetes. Positive and negative controls (patients with pancreatic carcinoma and type 2 diabetes, respectively) also were studied., Research Design and Methods: We examined 25 patients with autoimmune diabetes (16 with recently diagnosed type 1 diabetes, 9 with latent autoimmune diabetes in adults [LADA]), 6 with type 2 diabetes, and 7 with pancreatic carcinoma (the latter two groups were used as negative and positive controls, respectively). All patients underwent (99m)Tc-IL-2 scintigraphy and contrast-enhanced MRI of the pancreas. To validate positive controls, samples were taken from patients with pancreatic carcinoma during surgery for histological and immunohistochemical investigations., Results: Pancreatic accumulation of (99m)Tc-IL-2 was detected in patients with autoimmune diabetes (61% positive) and, notably, in 6 of 9 patients with LADA; semiquantitative evaluation of pancreatic uptake of (99m)Tc-IL-2 showed higher values in patients with autoimmune diabetes (both childhood and LADA) and pancreatic carcinoma than in those with type 2 diabetes (4.45 ± 1.99, 4.79 ± 1.1, and 4.54 ± 1.62 vs. 2.81 ± 0.63; P = 0.06, P = 0.01, and P = 0.04, respectively). In patients with pancreatic carcinoma, pancreatic interleukin-2 receptor expression correlated with pancreatic (99m)Tc-IL-2 uptake (r = 0.8; P = 0.01). In patients with LADA, (99m)Tc-IL-2 uptake inversely correlated with duration of disease (r = 0.7; P = 0.03)., Conclusions: Autoimmune diabetes in adults is associated with increased pancreatic (99m)Tc-IL-2 uptake, indicating the presence of insulitis, particularly within 1 year of the beginning of insulin therapy, similar to type 1 diabetes at diagnosis., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

B cells arise from stem cells precursor and develop through a tightly regulated and selective process that lead to the generation of different B cell populations such as transitional, mature, memory and plasma cells. These B cell subsets can be identified using flow cytometry by the expression of specific surface antigens. The growing knowledge of the pivotal role played by B cells in the development and progression of autoimmune diseases combined with the advances in monoclonal antibody technology, led in the last years to the generation of different biological agents targeting B cells. In this context, nuclear medicine can offer the possibility to use a panel of biologic radiopharmaceuticals for molecular imaging of inflammatory diseases. Radiopharmaceuticals bind to their targets with high affinity and specificity and have an excellent imaging diagnostic potential for the evaluation of disease activity, selection and monitoring of immune therapies. Several molecules have been radiolabelled for the imaging of T lymphocytes whereas, by now, the anti CD20 rituximab is the only biological therapy targeting B cells that demonstrated to be efficiently radiolabelled and used to detect inflammation in autoimmune patients.

Objective: Previous reports showed the reduction of dopamine transporter immunoreactivity in peripheral blood lymphocytes in Parkinson's disease. In this work, we sought to investigate the possible correlation between central and peripheral dopamine transporter immunoreactivity values in a group of 11 drug-naive patients with Parkinson's disease., Methods: Densitometric measurements of dopamine transporter immunoreactivity in peripheral blood lymphocytes was accomplished as described recently, using a monoclonal antidopamine transporter antibody. Dopamine transporter binding in the caudate and putamen nuclei was measured by means of (123)I-fluopane single-photon emission computed tomography in the same patients., Results: The results failed to show any significant correlation between dopamine transporter immunoreactivity in peripheral blood lymphocytes and the caudate or putamen dopamine transporter binding. Moreover, dopamine transporter immunoreactivity in peripheral blood lymphocytes was reduced also in the single patient with normal striatal dopamine transporter binding., Discussion: These results indicate the lack of correlation between central and peripheral dopamine transporter reduction in Parkinson's disease, using the methodologies applied herein. They therefore suggest that the two phenomena are unlikely to share a common pathogenetic mechanism.

Background and Aim: Osteomyelitis of the foot is the most commonly encountered complication in diabetic patients. Nuclear medicine techniques are usually complementary to radiology in the diagnosis of foot infections; they play an important role in various clinical situations. The aim of this study was to develop a practical guideline to describe the radiopharmaceuticals to be used for different clinical conditions and different aims in diabetic foot infection., Methods: In this study, we reviewed 57 papers (published between 1982 and 2004; 50 original papers and seven reviews) that described the imaging of the diabetic foot and examined a total of 2889 lesions. We performed data analysis to establish which imaging technique could be used as a 'gold standard' to diagnose infection, evaluate the extent of disease and monitor the efficacy of therapy., Results and Conclusion: We provide a guideline to assist in the selection of the optimal radiopharmaceuticals for different clinical conditions and different aims.

Discovery of osteitis may be delayed because of late appearance of X-ray signs in patients with diabetic foot. Scintigraphy with labelled leukocytes is able to detect flogosis but often misses bone involvement, due to inadequate resolution of Anger camera, the commonest detector used in nuclear medicine. Radioguided surgery and biopsy with high resolution scintigraphy (HRS) started to be studied since 2000: although this method had never been tested for planning and guiding diabetic foot surgery, in our opinion it can help early diagnosis and surgical treatment of diabetic foot. Five patients with diabetic foot and suspected infection were studied with standard 99mTc [HMPAO]-leukocyte scan. In the same patients 2 mm spatial resolution HRS was performed 24 hours after administration of labelled WBC, using our inch2 field-of-view portable mini-gammacamera. Operations were done just after the 24h scan and were guided with the portable high resolution device in the four patients who showed positive scan. Scintigraphy with Anger camera and HRS were positive in four patients. HRS showed a bar-shaped radioactivity corresponding to small phalanges, close to the main inter-digital hot spot. The presence of osteitis on phalanges that had been shown by HRS was confirmed at surgery, that was successfully driven with the high resolution mini-camera. In conclusion HRS is able to diagnose early osteitis of diabetic foot and to guide diabetic foot surgery.

Aim: Aim of the present study was to compare in vitro the labelling efficiency (LE) and cell viability (TBE) of autologous leukocytes labelled with (99m)Tc-SnF(2) and (99m)Tc-HMPAO, and to evaluate the quantity and quality of spontaneously released (99m)Tc (SR) from labelled cells at several time points after labelling., Methods: A total of 14 patients with different diseases and 18 normal subjects were included in this study. A blood sample was collected from each patient; purified autologous leukocytes were divided into 2 samples and labelled with (99m)Tc-SnF(2) and (99m)Tc-HMPAO. LE was evaluated at the end of labelling and TBE and SR were evaluated at 10 min and 1 h, 2 h and 4 h after labelling., Results: LE of (99m)Tc-SnF(2)-WBC was higher than (99m)Tc-HMPAO-WBC (61.2+/-18.7% and 43.3+/-11.3; p<0.0001) and we found an inverse correlation between blood glucose and labelling efficiency for both methods (p=0.02). Minimal differences were also observed between 2 methods after 10 min and 1 h, as far as the cell viability is concerned. The percentage of radioactivity spontaneously released from (99m)Tc-SnF(2)-WBC was significantly higher compared to (99m)Tc-HMPAO-WBC at each time point. Radioactivity released from labelled cells was predominantly (99m)Tc-SnF(2) and (99m)Tc-HMPAO with few free (99m)Tc (<20%)., Conclusion: Both radiopharmaceuticals are not toxic for WBC. Labelling with (99m)Tc-SnF(2) give a higher LE than with (99m)Tc-HMPAO; however, radiolabelled colloids are more released from labelled cells over a period of 4 h. While (99m)Tc-HMPAO is physiological excreted into gastrointestinal tract, (99m)Tc-SnF(2) can be re-uptaken in vivo by reticulo-endothelial cells of liver and spleen. These findings suggest that (99m)Tc-SnF(2)-WBC might be better than (99m)Tc-HMPAO-WBC for studying inflammatory bowel diseases.

Radiolabelled cytokines and chemokines are a new group of radiopharmaceuticals. These, by binding to specific receptors expressed on selected cell populations, enable the histological and functional characterization of immune-mediated processes, in vivo. Clinical studies have demonstrated the efficacy of using this type of scintigraphy in detecting sites of acute inflammation (infection) and chronic (T-cell-mediated) inflammation. Recent studies are focusing on the possible use of radiolabelled cytokines and chemokines for the biological characterization of cancer cells in vivo. In particular, the homing of metastases into specific tissues could depend on the chemoattraction of these tissues, mediated by soluble chemokines that bind to specific receptors expressed on cancer cells. These studies will generate a deeper knowledge of the molecular mechanism of tumor metastasis and lead to new therapies in nuclear medicine.

The health care financing decision are becoming increasingly complex in all health care environments. As a managed care becomes a greater percentage of overall business, accurate financial planning and decision making will be key components of viable organization. Therefore, the priority for health care systems is to manage their costs at the same time as maintaining the relationships they have with patients, providers, payors, and communities in order to have long term success and short term survival. Principal wedge to value an investment is to define a planning in order to identify the activities, to attribute costs to the activities, to fix a full cost for every performances and to examine fixed costs and variable costs. This is the key to achieve a economic balance.

Crohn's disease (CD) is a chronic inflammatory bowel disease that may involve the whole gut. Marked intestinal T cell and macrophage activation is a key feature of the disease. Polymorphonuclear cell infiltration is also observed in the diseased gut, mainly during active inflammation. Scintigraphic detection of granulocytes and activated lymphocytes infiltrating the gut wall may be useful in identifying a subgroup of patients with clinically inactive CD who are undergoing early clinical relapse. The aims of the present study were (a) to compare the effectiveness of scintigraphy with (99m)Tc-labelled interleukin-2 ((99m)Tc-IL2) and with (99m)Tc-HMPAO labelled granulocytes ((99m)Tc-WBC) in detecting the presence and extent of bowel inflammation in patients with long-term inactive CD (>12 months) and (b) to assess the accuracy of these techniques in predicting future disease relapse. We studied 29 patients with ileal and/or colonic CD in stable clinical remission (Crohn's Disease Activity Index <150 for at least 12 months) using both (99m)Tc-IL2 and (99m)Tc-WBC scintigraphy in order to evaluate the extent of acute and chronic inflammation in the bowel. Planar and single-photon emission tomography images were acquired in each patient at 1 h p.i. For quantitative analysis of (99m)Tc-IL2 uptake, the abdomen was divided into 32 regions of interest. Despite the absence of symptoms, 18 patients (62%) showed a positive (99m)Tc-IL2 and 18 (62%) a positive (99m)Tc-WBC scan. Only 12 patients (41.4% of the total group) were positive on both scans, and the sites of IL2 and granulocyte bowel uptake were usually located in different segments, indicating that in CD, acute and chronic inflammation can be present in different sites. As far as the prognostic role of the two scans in predicting future disease relapse is concerned, both (99m)Tc-IL2 and (99m)Tc-WBC scintigraphy showed a high negative predictive value (1.00 and 0.91, respectively) but a weak positive predictive value (0.44 and 0.39, respectively). Nevertheless, Kaplan-Meier curves generated between scintigraphic findings and time free from disease relapse were statistically different only for (99m)Tc-IL2 scintigraphy (log-rank test, P=0.013). These results indicate that (99m)Tc-IL2 scintigraphy can be useful in selecting CD patients in clinical remission who could benefit from preventive therapy to avoid disease relapse.

Because of the high prevalence of Trypanosoma cruzi infection in Latin America, antibody screening in blood banks is mandatory in this area. This screening may also become a concern in the U.S.A. considering the high frequency of Latin American donors. The tests usually employed (indirect hemagglutination, direct agglutination, immunofluorescence and latex agglutination assays) involve subjective interpretation of results and do not fit the automated procedures requirements of large laboratories. Thus, an enzyme immunoassay was developed using a mixture of antigens purified from the membrane and the cytoplasm of the parasite. Serum of plasma could be used as sample, in a procedure involving 90 min total incubation time and 2 washing steps. Results could be interpreted either spectrophotometrically or by the naked eye. The method was used to test 661 samples from patients undergoing different stages of Chagas' disease, 120 patients suffering other parasitosis and 880 normal subjects. Results were compared with those obtained with the methods mentioned above. The proposed test showed better reproducibility, specificity and sensitivity than those of reference methods, plus an objective interpretation of results and suitability to automation.

Transgenic Nicotiana benthamiana plants expressing the coat protein gene of cymbidium ringspot virus (CyRSV) were tested for resistance against infection with CyRSV. Transgenic plants showed resistance to infection only when the purified virions concentration in the inoculum was as low as 0.05 micrograms/ml. No protection was observed in transgenic plants inoculated with virion concentrations of 0.5 and 5.0 micrograms/ml or when the inoculum was in vitro synthesized genomic RNA.