High-Dose Intravenous Steroid Treatment Seems to Have No Long-Term Negative Effect on Bone Mineral Density of Young and Newly Diagnosed Multiple Sclerosis Patients: A Pilot Study.

High-dose intravenous steroid treatment (HDIST) represents the first choice of treatment for multiple sclerosis (MS) relapses. Chronic oral glucocorticoid (GC) administration correlates with bone loss whereas data regarding HDIST in MS are still conflicting. Twenty-five newly diagnosed MS patients (NDMSP) (median age: 37 years) were prospectively studied for the effects of HDIST on bone mineral density (BMD) and bone metabolism. Patients received 1000 mg methylprednisolone intravenously every day for 5 days followed by oral prednisolone tapering over 21 days. Bone metabolism indices were determined prior to GC, on days 2, 4, 6, and 90, and at months 6, 12, 18, and 24 post GC therapy. Femoral, lumbar-spine BMD, and whole-body measurement of adipose/lean tissue were assessed prior to GC-administration and then every six months. Ten patients completed the study. N-terminal-propeptide-procollagen-type-1 and bone-specific alkaline phosphatase showed a significant increase at day-90 (p < 0.05). A transient non-significant fall of BMD was observed at 6 months after GC-administration, which subsequently appeared to be restored. We conclude that HDIST seems not to have long-term negative effects on BMD, while the observed transient increase of bone formation markers probably indicates a high bone turnover phase to GC-administration. Additional prospective studies with larger sample size are needed.

Challenges and priorities in skeletal, gastrointestinal, hepatobiliary, genitourinary and lung scintigraphy during the COVID-19 pandemic.

On December 29, 2019, a hospital in the City of Wuhan, Hubei Province, in Central China, admitted four individuals with pneumonia. The hospital reported this occurrence to the local center for disease control (CDC), which lead Wuhan CDC staff to initiate a field investigation with a retrospective search for pneumonia patients. On December 31, 2019, the World Health Organization (WHO) was alerted by the Chinese authorities for several cases of pneumonia of unknown origin in the City of Wuhan. On January 7, 2020, a novel virus was identified as the causative agent, belonging to the Coronaviridae family (Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2). Within the same month, the virus spread to other provinces of China, as well as a number of neighbouring countries. On February 11, 2020, the WHO announced that the SARS-CoV-2 - caused infection would be called coronavirus disease 2019 (COVID-19). On February 15, 2020, the first death due to COVID-19 in Europe was reported; a Chinese tourist who died in France. The first COVID-19 case was diagnosed in Greece on February 26th. The WHO declared COVID-19 a pandemic on 11 March 2020. On March 12th, movie theaters, gyms and courtrooms were closed in Greece and on March 13th, with 190 confirmed cases and 1 death, malls, cafés, restaurants, bars, beauty parlors, museums and archaeological sites were also closed. So far, COVID-19 pandemic has affected the way people live and work globally, and has resulted in extreme strain on the healthcare systems worldwide. Most of the nuclear medicine studies are performed on an out-patient basis. Therefore, without effective implementation of the required preventive measures, there is a significant risk for viral transmission when visiting nuclear medicine departments, particularly in periods of high community spread.

Human white-fat thermogenesis: Experimental and meta-analytic findings.

White adipose tissue (WAT) thermogenic activity may play a role in whole-body energy balance and two of its main regulators are thought to be environmental temperature (Tenv) and exercise. Low Tenv may increase uncoupling protein one (UCP1; the main biomarker of thermogenic activity) in WAT to regulate body temperature. On the other hand, exercise may stimulate UCP1 in WAT, which is thought to alter body weight regulation. However, our understanding of the roles (if any) of Tenv and exercise in WAT thermogenic activity remains incomplete. Our aim was to examine the impacts of low Tenv and exercise on WAT thermogenic activity, which may alter energy homeostasis and body weight regulation. We conducted a series of four experimental studies, supported by two systematic reviews and meta-analyses. We found increased UCP1 mRNA (p = 0.03; but not protein level) in human WAT biopsy samples collected during the cold part of the year, a finding supported by a systematic review and meta-analysis (PROSPERO review protocol: CRD42019120116). Additional clinical trials (NCT04037371; NCT04037410) using Positron Emission Tomography/Computed Tomography (PET/CT) revealed no impact of low Tenv on human WAT thermogenic activity (p > 0.05). Furthermore, we found no effects of exercise on UCP1 mRNA or protein levels (p > 0.05) in WAT biopsy samples from a human randomized controlled trial (Clinical trial: NCT04039685), a finding supported by systematic review and meta-analytic data (PROSPERO review protocol: CRD42019120213). Taken together, the present experimental and meta-analytic findings of UCP1 and SUVmax, demonstrate that cold and exercise may play insignificant roles in human WAT thermogenic activity. Abbreviations: WAT:White adipose tissue; Tenv: Environmental temperature; UCP1: Uncoupling protein one; BAT: Brown adipose tissue; BMI:Body mass index; mRNA: Messenger ribonucleic acid; RCT: Randomized controlled trial; WHR: Waist-to-hip ratio; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-analyses; PET/CT: Positron Emission Tomography and Computed Tomography; REE: Resting energy expenditure; 18F-FDG: F18 fludeoxyglucose; VO2peak:Peak oxygen consumption; 1RM: One repetition maximum; SUVmax: Maximum standardized uptake value; Std: Standardized mean difference.

I-131 Postablation SPECT/CT Predicts Relapse of Papillary Thyroid Carcinoma more Accurately than Whole Body Scan.

BACKGROUND/AIM: The aim of the study was to prospectively compare I-131 postablation Whole Body scan (WBS) and Single Photon Emission Computerized Tomography/Computerized Tomography (SPECT/CT) scan on thyroid cancer patients. PATIENTS AND METHODS: Overall, 58 patients with papillary thyroid carcinoma were submitted to total thyroidectomy and I-131 remnant ablation. Post-ablation WBS and SPECT/CT scans performed on the same day were compared. Results of SPECT/CT were confirmed by neck and upper mediastinum ultrasound scan and on specific cases by a fully diagnostic CT scan, other tests and definitive histology acting as the gold standard. A total of 36/58 patients were followed-up for 5 years to detect relapse. RESULTS: Mac Nemar Chi square and Fisher's exact tests disclosed statistically significant differences between WBS and SPECT/CT scan, concerning cervical lymphadenopathy detection (p=0.031) and relapse prediction by NM stage (p=0.033), respectively; SPECT/CT was more accurate in both comparisons. CONCLUSION: In papillary thyroid carcinoma I-131 post-ablation SPECT/CT scan detects cervical lymphadenopathy and predicts relapse by NM stage more accurately than WBS.

Impact of renin-angiotensin-aldosterone system polymorphisms on myocardial perfusion: Correlations with myocardial single photon emission computed tomography-derived parameters.

BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) has an important role in atherosclerosis. We investigated the effects of six RAAS gene polymorphisms on myocardial perfusion. METHODS AND RESULTS: We examined 810 patients with known or suspected coronary artery disease (CAD) using stress-rest myocardial single-photon emission computed tomography. Summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), transient ischemic dilation (TID), and lung/heart ratio (LHR) were recorded. The following gene polymorphisms were investigated: angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M235T and T174M, angiotensin II type 1 receptor (AT1R) A1166C, renin (REN) C5312T, and angiotensin II type 2 receptor (AT2R) C3123A. The heterozygotes or homozygotes on ACE D allele were 7.54 times more likely to have abnormal SSS, while the AGT (T174M) heterozygotes were 5.19 times more likely to have abnormal SSS. The homozygotes of ACE D had significantly higher values on TID and LHR, while the AGT (T174M) heterozygotes had higher values on TID. The AT1R heterozygotes had greater odds for having SSS ≥ 3. The patients carried AT1R homozygosity of C allele had significantly higher values on TID, while heterozygotes of AT1R had significantly higher values on LHR. CONCLUSIONS: Among the polymorphisms investigated, ACE D allele had the strongest association with abnormal myocardial perfusion.

Performance and safety profile of regadenoson myocardial perfusion imaging: first experience in Greece.

OBJECTIVE: MPI can provide valuable information in the investigation of patients with known or suspected coronary artery disease. The stress component of the studies can be conducted with regadenoson, which was approved for clinical use in Greece in 2016. We investigated the performance and safety profile of regadenoson MPI based on our 7 months institutional experience. PATIENTS AND METHODS: We studied 96 consecutive patients (59 males, 37 females, mean age 70.35y.o, range: 46-87y.o.) referred to our department for a clinically indicated MPI study with pharmacological stress. Eleven patients suffered from chronic obstructive pulmonary disease. Patients underwent regadenoson stress test, combined with both stress and rest imaging. Data on the symptoms and electrocardiographic changes due to regadenoson administration were recorded. Symptoms were graded as 1-mild: a symptom that did not distress the patient, 2-moderate: a symptom that distressed the patient but it was self-limiting, or 3-severe: a symptom that distressed the patient requiring medical intervention. RESULTS: Regadenoson-related symptoms were reported in 56 patients and were: dyspnea, discomfort, dizziness, chest pain, epigastric pain, neck pain, headache, flushing, nausea, heartburn, weakness, and upper limbs numbness. The severity of symptoms was recorded as grade 1 in 30 patients, grade 2 in 25 patients, and grade 3 in 1 patient. Two or more different symptoms were reported in 28 patients. Ischemic electrocardiographic changes and arrhythmias were observed in 8 patients. CONCLUSION: Our findings support previously published data indicating the optimal safety profile of regadenoson MPI, even in the group of patients suffering from chronic obstructive pulmonary disease.

Bone Single Photon Emission/Computed Tomography in the Detection of Sacroiliitis in Seronegative Spondyloarthritis: A Comparison with Magnetic Resonance Imaging.

OBJECTIVE: Seronegative spondyloarthritis (SpA) is characterized by chronic inflammation affecting the axial skeleton, entheses and occasionally peripheral joints. The involvement of the sacroiliac joints, sacroiliitis, is considered as a pathognomonic radiographic finding. Magnetic resonance imaging (MRI) is the method of choice for its early detection. Bone scintigraphy (BS) is characterized by high sensitivity in the diagnosis of bone and articular diseases. Limited value of BS in the diagnosis of sacroiliitis may be attributed to the use of planar imaging. In the present study, we aimed to investigate the role of SPECT in SpA, compared to MRI. METHODS: Forty-three patients suffering from inflammatory back pain underwent MRI evaluation of the sacroiliac joints and BS, combined with SPECT in the same region, for the assessment of sacroiliitis. RESULTS: Bone SPECT revealed no findings of sacroiliitis in 11 patients, with total agreement with MRI. Findings of chronic lesions were demonstrated from both modalities in 2 patients. Bone SPECT and MRI findings were in concordance regarding the investigation of active sacroiliitis, with the exception of one patient with mild SPECT findings and negative MRI examination; the diagnosis of AS however, was established one year later, after a positive follow-up MRI. The evaluation of the planar imaging of the whole skeleton and SPECT imaging, revealed additional lesions. CONCLUSION: Bone SPECT is a reliable imaging method in the diagnosis of active sacroiliitis. Its application on planar BS, an economic and widely available diagnostic technique, appears to be a valuable aid for the clinician.

The potential role of Calcitonin Gene-Related Peptide (CGRP) in breast carcinogenesis and its correlation with 99mTc-(V)DMSA scintimammography.

OBJECTIVES: Experimental data suggest a role for calcitonin gene-related peptide (CGRP) in normal breast development and angiogenesis. This pilot study correlated CGRP with neoangiogenesis and the uptake of the tumor-seeking, proliferation-imaging radiotracer pentavalent technetium-99m dimercaptosuccinate (99mTc-(V)DMSA) in invasive and preinvesive breast lesions. METHODS: Among women evaluated preoperatively by 99mTc-(V)DMSA scintimammography, 29 invasive ductal carcinomas (IDCs) were retrospectively studied: 15 isolated (Group I); 14 mixed with preinvasive pathologies (ductal carcinoma in situ [DCIS] and/or epithelial hyperplasia [EH]; Group M). CGRP staining and neoangiogenesis were compared between invasive and DCIS/EH regions and were correlated. 99mTc-(V)DMSA displayed a diffusely increased uptake pattern corresponding to DCIS/EH; its lesion-to-background (L/B) ratio was compared between images acquired at 10 and 60 minutes and its retention ratio (RR) was correlated with CGRP. RESULTS: Seven of 15 group I and 10 of 14 group M patients (58.6% of the population) were CGRP-positive. CGRP was prevalent in the DCIS/EH component of mixed-lesions (even in the surrounding normal epithelium of nearly half), with declining intensity as advancing from DCIS/EH to high-grade IDC. Similarly, neoangiogenesis was considerably higher in DCIS/EH than in group I pure IDCs. A significant CGRP-neoangiogenesis correlation was verified only in group I. The diffuse 99mTc-(V)DMSA uptake exhibited significant, time-related L/B increase and a RR positively correlating with CGRP. CONCLUSIONS: CGRP expression and neoangiogenesis are intensified in mixed invasive-preinvasive breast lesions; an underlying relation may exist, requiring further investigation. CGRP also appears associated with 99mTc-(V)DMSA's propensity to depict preinvasive pathologies. This relationship could denote an additional proliferative role for CGRP.

Clinical usefulness of attenuation and scatter correction in Tl-201 SPECT studies using coronary angiography as a reference.

INTRODUCTION: The aim of this investigation was to evaluate the clinical usefulness of both attenuation and scatter correction in 201Tl SPECT studies. METHODS: We studied 102 patients (76 males, 26 females, mean age 54 years) who underwent coronary angiography prior to or after a scintigraphic examination. A 201Tl one-day protocol was used. Simultaneous transmission-emission images were obtained by a gamma-camera equipped with an attenuation and scatter correction system based on two moving collimated 153Gd rod sources. Stress and delay reconstructed images, uncorrected for attenuation and scatter, were diagnosed. One month later, stress and delay reconstructed images corrected for attenuation and scatter were diagnosed by the same readers. The results were compared using the coronary angiography findings as reference. A stenosis 50% or larger was considered significant. RESULTS: Attenuation and scatter corrected images demonstrated a significant increase in specificity for findings in the right coronary artery territory, i.e. 89% vs. 41% for uncorrected images (p < 0.05), with a non-significant loss in sensitivity from 96% to 89%. When we split the population on a gender basis, statistically significant differences in specificity between corrected and non-corrected images were observed in the left anterior descending territory for the females (100% vs. 42%) and in the right coronary artery territory for males (87% vs. 26%). CONCLUSION: Attenuation and scatter correction in 201Tl SPECT studies may significantly decrease false positive lesions in the inferior wall as well as in the anterior in females.

Scintigraphy with technetium-99m methoxyisobutylisonitrile in multiple myeloma patients: correlation with the International Staging System.

(99m)Tc-2-methoxyisobutylisonitrile ((99m)Tc-MIBI) scintigraphy has been suggested in multiple myeloma (MM) patients. According to the International Staging System (ISS), serum b2-microglobulin (Sbeta(2)M) and serum albumin (SA) are dominant predictive factors and different cut-off values of these factors can separate patients into various stages of the disease. The purpose of this study was to assess the relationship between ISS staging, by Sbeta(2)M and SA, and the (99m)Tc-MIBI scan findings. Twenty-five MM patients have been studied. Eighteen patients were at stage I, three at stage II and four at stage III of MM. (99m)Tc-MIBI scans were obtained and scored according to intensity (I) and extent (E) of the radiotracer uptake. A summed score (S) for the (99m)Tc-MIBI scan was calculated for each patient. A statistically significant negative correlation between E, I and S uptake scores versus the SA levels (P=0.004, 0.049 and 0.018 respectively), as well as a statistically significant positive correlation between E and S scores and the Sbeta(2)M levels (P=0.012 and 0.032) were detected. A statistically significant difference between the E and S uptake scores among the MM patients examined for every stage separately was also found (P=0.007 and 0.024 respectively). The gradual increase of the E and S scores across the three stages of MM was also significant (P=0.003 and 0.021 respectively), despite the relatively small number of patients in stages II and III. In seven patients who died at the end of the follow-up period all three scores were significantly increased as compared to the scores of the patients who remained alive at that time. In conclusion, this study provides additional evidence that (99m)Tc-MIBI scan not only reflects myeloma disease activity in bone marrow but it is also well correlated with the Sbeta(2)M and SA levels according to ISS.

Tc-99m pentavalent DMSA scintigraphy in myelofibrosis detection.

In a 62-year-old man with medullary carcinoma of the thyroid, a postoperative Tc-99m dimercaptosuccinic acid [(V) DMSA] study was requested. In the Tc-99m (V) DMSA scan. no abnormalities, indicating local recurrence or metastatic disease, were observed. However, there was increased uptake in the spleen and liver and significantly diffusely increased uptake in the bone marrow. The patient also had a history of myelofibrosis and these findings appear to have been the result of this pathology.

Scintimammographic detection of usual ductal breast hyperplasia with increased proliferation rate at risk for malignancy.

OBJECTIVES: To estimate whether breast uptake of (99m)Tc-(V)DMSA and (99m)Tc-sestamibi in usual ductal epithelial breast hyperplasia (UDH) and apocrine metaplasia is related to cell proliferation rate (Ki-67) and oestrogen receptor (ER) expression, both of which are associated with the potential risk of evolving to malignancy. METHODS: Among patients referred for suspicious breast findings on palpation and/or mammography and evaluated preoperatively with both radiopharmaceuticals, we retrospectively studied 17 (10 with UDH: group I; and seven with apocrine metaplasia: group II). Lesion-to-background (L/B) ratios in early and late acquisitions were calculated for both radiotracers in both groups, as well as their retention ratios. Ki-67 and oestrogen receptor expression were determined immunohistochemically. The late L/B ratios between the two tracers were compared, as were the late ratios for each tracer between Ki-67 < or = 3% and > 3%, and between ER < or = 15% and > 15%. Linear regression analysis was also performed between L/B and retention ratios and Ki-67 expression. RESULTS: There was a significant increase of the (99m)Tc-(V)DMSA L/B ratio in late images as compared to the early images in group I (P<0.05), while in group II it was not significantly increased (P=0.084). (99m)Tc-sestamibi ratios did not demonstrate variability over time in either group (P=0.156 and 0.274, respectively). Significant coefficient correlation was found between the (99m)Tc-(V)DMSA L/B(late) ratios and retention ratios and Ki-67 levels only for group I (r=0.889, P<0.001 and r=0.802, P<0.01, respectively). The (99m)Tc-(V)DMSA L/B(late) ratios in group I were significantly higher when Ki-67 > 3% than when Ki-67 < or = 3% (P=0.016) but did not differ considerably between ER > 15% and < or = 15% (P=0.732). CONCLUSION: (99m)Tc-(V)DMSA uptake in UDH correlates with Ki-67 expression. This could prove useful in identifying women with benign but high-risk breast pathologies who might benefit from chemoprophylaxis.

Increased serum carbohydrate antigen 19-9 in relapsed ductal breast carcinoma.

Increased serum carbohydrate antigen (CA) 19-9 is a quite uncommon manifestation of breast cancer both on early disease and on relapse. A 53-year-old woman with invasive ductal breast carcinoma underwent left-sided mastectomy. Two years later she palpated a subcutaneous mass at the mastectomy scar, arousing suspicion of local relapse. Surgery and histopathology revealed infiltration by breast adenocarcinoma and she was treated with chemotherapy. At that time serum tumor markers, carcinoembryonic antigen (CEA) and CA 15-3 were within normal range. Over the next six months she displayed an increase of serum CEA while serum CA 15-3 remained within normal range. In an attempt to search for a second neoplasm possibly of gastrointestinal (GI) origin, abdominal computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangio-pancreatography (MRCP), endoscopy of the upper GI tract and colonoscopy were performed, as well as measurement of serum CA 19-9. While no indication of a GI neoplasm was detected, she displayed an over 10-fold increase of serum CA 19-9. The patient had also an X-ray mammography and technetium-99m hexakis-2-methoxyisobutylisonitrile ((99m)Tc-MIBI) scintimammography (SM). Whilst mammography was negative for contralateral disease recurrence, SM was suggestive of axillary lymph node involvement. Axillary lymph node dissection confirmed an extensive metastatic infiltration of these nodes by breast adenocarcinoma. Three months later serum CA 19-9 and CEA became normal. The interest of this case lies on the unexpected high serum CA 19-9 values found in a breast relapsed adenocarcinoma and in the important contribution of SM in diagnosing the axillary lymph node metastatic infiltration.

Combined use of 99mTc-sestamibi and 99mTc-V-DMSA in the assessment of chemotherapy effectiveness in patients with multiple myeloma.

UNLABELLED: This study determined the role of the combined use of (99m)Tc-sestamibi and (99m)Tc-pentavalent dimercaptosuccinic acid (V-DMSA) scintigraphy in evaluating the effectiveness of chemotherapy in patients with multiple myeloma. METHODS: In 20 patients with multiple myeloma who had received or were receiving chemotherapy, (99m)Tc-sestamibi and (99m)Tc-V-DMSA scanning was performed to evaluate the effectiveness of chemotherapy. RESULTS: In group A (11 patients with active disease), 42 (99m)Tc-sestamibi-positive lesions were found. Thirty-seven of those lesions were also positive for (99m)Tc-V-DMSA uptake, as were 16 additional lesions (nonactive) (NAL). Thus, in group A, the total number of positive lesions (TPL) detected was 58 and the NAL/TPL ratio was 16:58. In group B (9 patients in remission), 5 (99m)Tc-sestamibi-positive lesions were found. A further 22 lesions were also positive for (99m)Tc-V-DMSA uptake. Thus, in group B, the NAL/TPL ratio was 22:27. Therefore, the NAL/TPL ratios considered to represent effectively treated lesions were 27.6% and 81.5% for groups A and B, respectively. CONCLUSION: Combined use of the 2 agents allows the effectiveness of chemotherapy to be evaluated through a comparison of NAL and TPL multiple myeloma lesions even in the absence of a baseline study.