Comparison between viral vector and mRNA based COVID-19 vaccination in prevalence and severity of regional immune reactions, and 18F-FDG PET/CT features.

Objectives: The coronavirus pandemic caused by SARS-CoV-2 commenced in late 2019, and global wide vaccination appears to be the only reasonable solution to fight this dreadful virus. There are two main types of COVID-19 immunization using viral vector and mRNA-based vaccines. However, the impact of each of type on 18F-FDG PET/CT needs to be accurately assessed. This study aimed to compare the 18F-FDG PET/CT features of these two types of COVID-19 vaccines. Methods: A total of 188 patients referred for 18F-FDG PET/CT with a recent history of either BioNTech/Pfizer or AstraZeneca COVID-19 vaccination, and a control group of 40 patients with no history of any type of recent vaccination, were included in the study. 18F-FDG PET/CT studies of vaccinated patients assessed for injection site uptake and regional nodal and systemic reactions post vaccination. The data were compared to the control group and to the contralateral side for each patient. The findings were compared between patients who received Pfizer and AstraZeneca vaccines. Results: 18F-FDG PET/CT was semiquantitatively positive in 50.5% of the studied population for vaccine-related features. The ipsilateral axillary and infra- and supraclavicular lymph nodes were significantly larger in size and exhibited higher metabolic activity compared to the contralateral lymph nodes after both types of vaccination. The prevalence of regional nodal reactions post Pfizer and AstraZeneca vaccination was 39% and 17.9% on visual, and 61% and 47.6% on semiquantitative assessments, respectively. Patients receiving the Pfizer vaccine exhibited higher metabolic activity in the ipsilateral regional lymph nodes (p<0.05). No significant difference in the intensity of regional nodal reaction post vaccination was noted between the first four weeks. Conclusion: Significant local and regional nodal reactions are observed after both viral vector and mRNA COVID-19 vaccination with a tendency to extend toward the infra- and supraclavicular nodal stations but not to the pulmonary hilum. The greater intensity and extension of the nodal reaction after Pfizer vaccination suggests a higher possibility of false-positive results on 18F-FDG PET/CT studies using mRNA vaccination technology.

Prognostic value and optimal threshold of first thyroglobulin in low/intermediate risk DTC.

BACKGROUND: The aim of this study was to define prognostic value and optimal threshold of first thyroglobulin (fTg) measured after thyroidectomy and just before radio-iodine therapy (RIT), in low/intermediate risk patients with differentiated thyroid cancer (DTC). METHODS: This is a retrospective study in 383 patients with DTC who were treated with surgery followed by RIT. Response to treatment was assessed 1 and 2 years after RIT. Odds ratio of different risk factors like age, sex, TNM stage, fTg and Anti-Tg Ab were compared between patients with and without incomplete response 1 and 2 years after treatment. Receiver operating curve analysis was used for definition of optimal fTg cut off for detection of incomplete response. RESULTS: 218 female and 55 male with DTC had negative anti-Tg antibody (mean age: 37.5±14.5 years) and analyzed separately. fTg≥33.5 ng/mL and fTg/TSH ratio of ≥0.36 had the optimal sensitivity and specificity for detection of incomplete response 1 and 2 years after treatment. fTg<33.5 ng/mL had NPV of 98.5% for exclusion of distant metastases. Patients with fTg≥33.5 ng/mL had longer "time to excellent response" (3.6±2.3 vs. 2.0±1.8 yrs) and needed more additional treatments compared to patients with fTg<33.5 ng/mL. Multivariate analysis showed that fTg was the most potent risk factor for prediction of treatment failure 1 and 2 years after RIT. CONCLUSIONS: fTg of ≥33.5 ng/mL was the most important risk factor for prediction of treatment failure after RIT and could be included in decision algorithms regarding intensity of treatments in low/intermediate risk patients with DTC.

The value of 18F-FDG PET/CT for predicting or monitoring immunotherapy response in patients with metastatic melanoma: a systematic review and meta-analysis.

PURPOSE: To investigate the ability of 18F-FDG PET/CT to assess the response of patients with metastatic melanoma to immunotherapy. METHODS: A comprehensive search of the literature for studies examining the prognostic value of 18F-FDG PET/CT in monitoring the response of patients with metastatic melanoma to immunotherapy was performed. We also screened the references of the selected articles to identify any other relevant studies. Detailed data were extracted and categorized. Comprehensive meta-analysis software was used for analysis. RESULTS: Twenty four eligible articles were included in the systematic review. Based on the baseline 18F-FDG PET/CT imaging, the pooled hazard ratios of MTV, SLR, SUV/SULmax, SUV/SULpeak, and TLG for overall survival (OS) were 1.777 (95%CI: 1.389-2.275, p < 0.001), 3.425 (95%CI: 1.707-6.869, p = 0.001), 0.941 (95%CI: 0.599-1.477, p = 0.791), 1.704 (95%CI: 1.253-2.316, p = 0.016), and 1.755 (95%CI: 1.315-2.342, p < 0.001), respectively. The conventional and modified response assessment criteria exhibited a pooled sensitivity of 64% (95%CI: 46-79%) and 94% (95%CI: 81-99%) and a pooled specificity of 80% (95%CI: 59-93%) and 84% (95%CI: 64-95%), respectively, for the early 18F-FDG PET/CT scan. On the other hand, based on the late 18F-FDG PET/CT scan, the pooled sensitivity of 67% (95%CI: 35-90%) and 92% (95%CI: 73-99%) and pooled specificity of 77% (95%CI: 56-91%) and 76% (95%CI: 50-93%) were observed for the conventional and modified criteria, respectively. PET-detectable immune-related adverse events (irAEs) were associated with the response to therapy. CONCLUSIONS: The baseline SUVpeak, MTV, and TLG parameters represent promising predictors of the final response of metastatic melanoma patients to immunotherapy. Modified response assessment criteria are potentially an appropriate method for monitoring immunotherapy. irAEs are also valuable for predicting eventual clinical benefit of treatment.

Response Evaluation and Survival Prediction After PD-1 Immunotherapy in Patients with Non-Small Cell Lung Cancer: Comparison of Assessment Methods.

Immunotherapy using programmed death-1 blockers is a promising modality for non-small cell lung cancer (NSCLC). Therefore, defining the most accurate response criteria for immunotherapy monitoring is of great importance in patient management. This study aimed to compare the correlation between survival outcome and response assessment by PERCIST, version 1.0; immunotherapy-modified PERCIST (imPERCIST); RECIST, version 1.1; and immunotherapy-modified RECIST (iRECIST) in NSCLC patients. Methods: Seventy-two patients with NSCLC who were treated with nivolumab or pembrolizumab and had baseline and follow-up 18F-FDG PET/CT data were analyzed. The patients were categorized into responders (complete or partial response) and nonresponders (stable or progressive disease) according to PERCIST1 and PERCIST5 (analyzing the peak SUV normalized by lean body mass [SULpeak] of 1 or up to 5 lesions), imPERCIST1, imPERCIST5, RECIST, and iRECIST. The correlation between achieved response and overall survival (OS) was compared. Results: The overall response rate and the overall disease control rate of the study population were 29% and 74%, respectively. The OS and progression-free survival (PFS) of patients with complete and partial response were statistically comparable. The OS and PFS were significantly different between responders and nonresponders (20.3 vs. 10.6 mo, P = 0.001, for OS and 15.5 vs. 2.2 mo, P < 0.001, for PFS, respectively). Twenty-three (32%) patients with progressive disease according to PERCIST5 had controlled disease according to imPERCIST5; follow-up of patients showed that 22% of these patients had pseudoprogression. The overall incidence of pseudoprogression was 7%. The response rate was 25% and 24% according to PERCIST1 and PERCIST5 (P = 0.2) and 32% and 29% according to imPERCIST1 and imPERCIST5 (P = 0.5), respectively, indicating no significant difference between analyzing the SULpeak of only the most 18F-FDG-avid lesion and analyzing up to the 5 most 18F-FDG-avid lesions. Conclusion: The achieved response by all conventional and immunotherapy-modified methods correlated strongly with patients' survival outcome, with significantly longer OS and PFS in responders than in nonresponders according to all assessed definitions. The most 18F-FDG-avid lesion according to PERCIST and imPERCIST accurately reflects the overall metabolic response.

Extraosseous Accumulation of Technetium-99m-Methyl Diphosphonate (99mTc-MDP) in a Child with ALL: A Case Report.

Extraosseous accumulation of technetium-99m-methyl diphosphonate (99mTc-MDP) on bone scan is not common. This phenomenon is often attributed to abnormality of calcium metabolism and has been reported in a variety of conditions including metabolic diseases and malignancies. A five years old boy is presented here, who was admitted to the pediatric emergency suffering from fatigue, respiratory symptoms, weight loss, intermittent fevers, anorexia, nausea and vomiting, edema of legs and abdominal distension for one month. The initial laboratory analysis revealed hypercalcemia. The patient was referred for whole body bone scan with suspicion of malignancy and bone metastasis. The bone scan revealed highly increased radiotracer uptake in both lungs in the perfusion and blood pool phases. Delayed images also showed increased activity in lungs and gastric wall. The skeleton was not seen clearly. Bone marrow aspiration was done and established the diagnosis of ALL. The patient deceased due to respiratory failure 20 days later. Diffuse lung uptake in this patient was consistent with respiratory failure and poor prognosis. It is reported that bone scan may be useful for assessment of the extent of metastatic calcification and may establish suitable management to prevent organ failure.

Comparison of treatment efficacy 1 and 2 years after thyroid remnant ablation with 1110 versus 5550 MBq of iodine-131 in patients with intermediate-risk differentiated thyroid cancer.

BACKGROUND: Radioiodine ablation may be associated with improved survival in patients with intermediate-risk follicular cell differentiated thyroid cancer (FCDTC). The aim of this study was to compare ablation efficacy of 1110 versus 5500 MBq of iodine-131 (I) in FCDTC patients with intermediate risk. METHODS: Thirty-nine patients with intermediate-risk FCDTC (T3N0, T1-2N1b and T1-3N1a) were treated with 1110 MBq of I and compared with 43 age-matched and sex-matched patients who received 5550 MBq of I. Patients with invasive histology, extensive lymph node involvement, and preablation thyroglobulin (Tg) of more than 100 ng/ml were excluded from the study. All patients underwent total or near total thyroidectomy with or without lymph node dissection. Response to treatment was evaluated 1 and 2 years after I treatment. RESULTS: We studied four male and 78 female patients, age range 21-69 years. Preablation Tg level was 12.7±17.8 and 15.8±22.6 ng/ml in patients in the low-dose and high-dose groups, respectively (P=0.48). Anti-Tg antibody level as well as T and N staging were not significantly different in the two groups (P>0.2). One and 2 years after treatment, an excellent response was noted in 19 and 22 patients in the low-dose group and in 16 and 23 patients in the high-dose group, respectively (P>0.3). Using logistic regression analysis, preablation Tg was the only significant factor in the prediction of an incomplete response 2 years after therapy. CONCLUSION: 1110 MBq of I was as effective as 5550 MBq of I in the treatment of FCDTC patients with intermediate risk 1 and 2 years after therapy.

Ethnicity, Clothing Style, and Body Mass Index are Significant Predictors of Vitamin D Insufficiency in Germany.

OBJECTIVE: To analyze risk factors for vitamin D insufficiency in Germany with respect to ethnicity, sex, and clothing style. METHODS: We analyzed the routine diagnostic work-ups of 1,231 adult (45.9 ± 17.9 years old) German (n = 1,034) and Turk residents (n = 197) referred with nonspecific symptoms to the Thyroid Centers at St. Elisabeth-Hospital in Dorsten, Germany and Bottrop, Germany to assess for metabolic diseases. All subjects underwent a routine examination that consisted of a questionnaire, lab tests for 25-hydroxyvitamin-D (25OHD), and thyroid profile. Turk females with traditional clothing (headscarf and covered legs and arms) were considered to wear "covered clothing." Logistic-regression was performed to identify factors that could predict vitamin D deficiency (<20 ng/mL) and insufficiency (20-30 ng/mL). RESULTS: Vitamin D insufficiency was seen in 33% of Germans and 74.1% of Turks, and vitamin D deficiency was present in 11.3% and 44.2% of Germans and Turks, respectively (P<.001). The mean 25OHD value in Turk females with covered clothes was lower than that in Turk females with conventional clothing (16.3 ± 12.3 vs. 27.2 ± 15.8, P<.001). Vitamin D insufficiency was present in 86.0% of Turk females with covered clothing versus 62.8% with conventional clothing (odds ratio [OR] = 3.6, P = .002). Ethnicity, body mass index (BMI), and clothing style were significant predictors of vitamin D deficiency and insufficiency by logistic regression (P<.001). CONCLUSIONS: (1) Vitamin D insufficiency among Turk residents in Germany is higher compared to Germans. The highest prevalence was present in Turk females with covered clothing. (2) Monitoring vitamin D in Turk residents in Germany is warranted. (3) Vitamin D supplements and access to facilities with sunlight exposure for females with covered clothing and all individuals with poor diets or limited access to sun exposure may prevent future health burden due to vitamin D insufficiency.

Treatment efficacy of (153)Sm-EDTMP for painful bone metastasis.

INTRODUCTION: Involvement of the skeleton can cause an excruciating pain in two-thirds of terminal patients with a history of malignancy. Due to several limitations of other therapies, such as analgesics, bisphosphonates, chemotherapy, hormonal therapy and external beam radiotherapy; bone-seeking radiopharmaceuticals have an important role in palliation of pain from bone metastases. Although these kinds of therapies have many advantages including the ability to treat multiple sites of tumoral involvement simultaneously, no significant confliction with other treatments, ease of administration and the potential to be used repetitively; in Iran using of this modality is not widely practiced. In this study we evaluated the clinical usefulness of Sm-153 lexidronamfor pain management of bone metastases. METHODS: 28 patients (14 males and 14 females) aged 38-77 years with a history of painful bone metastases caused by different cancers, not responding to conventional treatments were included in the study. All patients had a recent whole body bone scan indicating multiple bone metastases. 1 mCi/Kg Sm-153 lexidronam was injected intravenously to the patients. Whole body scintigraphy was done 3 or 18 hours post injection. Pain relief and quality of life have been evaluated by analog pain scale and Karnofsky index every week, respectively. Also, all patients were evaluated for hematological toxicity every two weeks. Active follow ups were performed. RESULTS: 43% of patients showed the presence of the flare phenomenon during the first three days after Sm injection with a mean duration of 2.2 days. The pain relief began between 2 and 16 days post injection and the duration of pain palliation was in the range of 4 to 32 weeks (mean±SD=15.22±7.8). 64.3% of patients showed complete relief of pain and 21.4% achieved partial response to therapy. (Over all response to therapy was 85.7%). The lowest amount of peripheral blood cells was detected in the fourth week for RBCs and in the 6th week for WBCs and PLTs. No one experienced hematological toxicity induced problems. CONCLUSION: Sm-153 lexidronam is an effective treatment for painful bone metastases. The complication rate is low and the quality of life of the patients after treatment would be significantly improved.

Evaluation of the clearance characteristics of various microspheres in the human nose by gamma-scintigraphy.

The nasal cavity possesses many advantages as a site for drug delivery, such as; ease of administration, applicability for long-term treatments and a large surface area for absorption. One important limiting factor for nasal drug delivery is the limited time available for absorption within the nasal cavity due to mucociliary clearance. Several drug delivery systems including different kinds of microspheres have been tried for encapsulation of drugs and increasing the residence time in nasal cavity. In this study the clearance rate of three kinds of microspheres (Alginate, PLGA, and Sephadex) was determined by gamma-scintigraphy with lactose powder being used as negative control. (99m)Tc labeled microspheres were prepared using technetium pertechnetate in the presence of a potent reducing agent, stannus chloride. The labeling procedure was set in a manner that each 3-5 mg of microspheres contained 2 MBq of radioactivity. Labeling efficiency was calculated by paper chromatography using acetone as a mobile phase. Each delivery system containing 2 MBq of activity was administered into right nostril of four healthy volunteers and 1 min static views were repeated each half an hour until 4 h. Clearance rates were compared using two regions of interest (ROIs); the initial site of deposition of particles, and all of the nasopharynx region. The clearance rate of each one of microspheres was calculated after applying the physical decay corrections. The mean labeling efficiencies for Alginate, PLGA, and Sephadex microspheres were calculated as 60%, 59%, and 74%, respectively. The cleared percent of formulations from nasopharynx region after 4 h was determined as follows: PLGA microspheres 48.5 +/- 8.2%; Alginate microspheres 45.0 +/- 0.8%; Sephadex microspheres 63.1 +/- 3.4%; lactose powder 74.5 +/- 4.9%. Alginate and PLGA microspheres showed the lowest clearance rate compared to lactose powder (P < 0.0001 and P < 0.001, respectively), followed by Sephadex microspheres (P < 0.01). The clearance profiles of formulations from deposition ROI and nasopharynx ROI were identical. This study shows that Alginate and PLGA microspheres have the highest mucoadhesion properties and are suitable nasal delivery systems. Futhermore, this study proves that limiting step for the nasal clearance of nasally administered particulate systems is their dislocation from the initial site of deposition, and their following interactions with mucus layer in the rest of the nasal passage does not significantly affect the clearance time.