Amichay Meirovitz - Academia.edu (original) (raw)
Papers by Amichay Meirovitz
EJNMMI Physics, Feb 12, 2021
Background: Image quality and quantitative accuracy of positron emission tomography (PET) depend ... more Background: Image quality and quantitative accuracy of positron emission tomography (PET) depend on several factors such as uptake time, scanner characteristics and image reconstruction methods. Ordered subset expectation maximization (OSEM) is considered the gold standard for image reconstruction. Penalized-likelihood estimation (PL) algorithms have been recently developed for PET reconstruction to improve quantitation accuracy while maintaining or even improving image quality. In PL algorithms, a regularization parameter β controls the penalization of relative differences between neighboring pixels and determines image characteristics. In the present study, we aim to compare the performance of Q.Clear (PL algorithm, GE Healthcare) and OSEM (3 iterations, 8 subsets, 6-mm post-processing filter) for 68 Ga-DOTATATE (68 Ga-DOTA) PET studies, both visually and quantitatively. Thirty consecutive whole-body 68 Ga-DOTA studies were included. The data were acquired in list mode and were reconstructed using 3D OSEM and Q.Clear with various values of β and various acquisition times per bed position (bp), thus generating images with reduced injected dose (1.5 min/bp: β = 300-1100; 1.0 min/bp: β = 600-1400 and 0.5 min/bp: β = 800-2200). An additional analysis adding β values up to 1500, 1700 and 3000 for 1.5, 1.0 and 0.5 min/bp, respectively, was performed for a random sample of 8 studies. Evaluation was performed using a phantom and clinical data. Two experienced nuclear medicine physicians blinded to the variables assessed the image quality visually. Results: Clinical images reconstructed with Q.Clear, set at 1.5, 1.0 and 0.5 min/bp using β = 1100, 1300 and 3000, respectively, resulted in images with noise equivalence to 3D OSEM (1.5 min/bp) with a mean increase in SUV max of 14%, 13% and 4%, an increase in SNR of 30%, 24% and 10%, and an increase in SBR of 13%, 13% and 2%. Visual assessment yielded similar results for β values of 1100-1400 and 1300-1600 for 1.5 and 1.0 min/bp, respectively, although for 0.5 min/bp there was no significant improvement compared to OSEM. Conclusion: 68 Ga-DOTA reconstructions with Q.Clear, 1.5 and 1.0 min/bp, resulted in increased tumor SUV max and in improved SNR and SBR at a similar level of noise compared to 3D OSEM. Q.Clear with β = 1300-1600 enables one-third reduction of acquisition time or injected dose, with similar image quality compared to 3D OSEM.
Journal of Thoracic Oncology
Research Square (Research Square), Dec 11, 2020
Background: Image quality and quantitative accuracy of positron emission tomography (PET) depend ... more Background: Image quality and quantitative accuracy of positron emission tomography (PET) depend on several factors such as uptake time, scanner characteristics and image reconstruction methods. Ordered subset expectation maximization (OSEM) is considered the gold standard for image reconstruction. Penalized-likelihood estimation (PL) algorithms have been recently developed for PET reconstruction to improve quantitation accuracy while maintaining or even improving image quality. In PL algorithms, a regularization parameter β controls the penalization of relative differences between neighboring pixels and determines image characteristics. In the present study, we aim to compare the performance of Q.Clear (PL algorithm, GE Healthcare) and OSEM (3 iterations, 8 subsets, 6-mm post-processing filter) for 68 Ga-DOTATATE (68 Ga-DOTA) PET studies, both visually and quantitatively. Thirty consecutive whole-body 68 Ga-DOTA studies were included. The data were acquired in list mode and were reconstructed using 3D OSEM and Q.Clear with various values of β and various acquisition times per bed position (bp), thus generating images with reduced injected dose (1.5 min/bp: β = 300-1100; 1.0 min/bp: β = 600-1400 and 0.5 min/bp: β = 800-2200). An additional analysis adding β values up to 1500, 1700 and 3000 for 1.5, 1.0 and 0.5 min/bp, respectively, was performed for a random sample of 8 studies. Evaluation was performed using a phantom and clinical data. Two experienced nuclear medicine physicians blinded to the variables assessed the image quality visually. Results: Clinical images reconstructed with Q.Clear, set at 1.5, 1.0 and 0.5 min/bp using β = 1100, 1300 and 3000, respectively, resulted in images with noise equivalence to 3D OSEM (1.5 min/bp) with a mean increase in SUV max of 14%, 13% and 4%, an increase in SNR of 30%, 24% and 10%, and an increase in SBR of 13%, 13% and 2%. Visual assessment yielded similar results for β values of 1100-1400 and 1300-1600 for 1.5 and 1.0 min/bp, respectively, although for 0.5 min/bp there was no significant improvement compared to OSEM. Conclusion: 68 Ga-DOTA reconstructions with Q.Clear, 1.5 and 1.0 min/bp, resulted in increased tumor SUV max and in improved SNR and SBR at a similar level of noise compared to 3D OSEM. Q.Clear with β = 1300-1600 enables one-third reduction of acquisition time or injected dose, with similar image quality compared to 3D OSEM.
Harefuah, Jul 1, 2021
Aims: The aim of this study was to evaluate the predictive power of the absorbed dose to kidneys ... more Aims: The aim of this study was to evaluate the predictive power of the absorbed dose to kidneys after the first course of treatment with [177Lu]-DOTA-TATE on the cumulative kidney absorbed dose after 3 or 4 cycles of treatment. Background: Peptide receptor radionuclide therapy (PRRT) with [177Lu]-DOTA-TATE is an effective treatment for somatostatin receptor positive neuroendocrine tumors (NETs). Post-treatment scans (PTS) are required after each cycle of treatment for personalized radiation dosimetry in order to calculate the dose to organs and tumors and to ensure a cumulative absorbed dose to kidneys under a safety threshold of 25 Gy. Methods: A total of 187 patients who completed treatment and underwent PTS for dosimetry calculation were included in this retrospective study. The correlation between the cumulative absorbed dose to the kidneys after completion of treatment and the absorbed dose after the first cycle(s) was studied. Multilinear regression analysis was performed to predict the cumulative absorbed dose by the kidneys in the subsequent cycles. An algorithm for the follow-up of the kidney absorbed dose is proposed. Results: When the absorbed dose to kidneys after the first cycle of treatment is below 5.6 Gy, four cycles of treatment can be safely administered with a cumulative dose less than 25 Gy (p < 0.1). For the remaining patients, the cumulative dose absorbed after 3 or 4 cycles of treatment can be predicted after the second cycle of treatment. This protocol enabled early decisions on the number of treatment cycles and reduced the number of post-treatment SPECT/CT studies for dosimetry in 34% of patients, as well as hospitalization time for 56% of the treatment cycles. Conclusions: Assessment of the kidney absorbed dose after PRRT can be simplified with the algorithm presented in this study. This approach enabled early decisions on the number of therapy cycles in 75% of patients. Discussion: The validity of these results is limited to the protocol of dosimetry calculation used in our institution. Implementation in other centers may require standardization of the acquisition parameters and the dosimetry protocol.
The main known function of Nudix hydrolase 2 (Nudt2) is to hydrolyze the secondary messenger diad... more The main known function of Nudix hydrolase 2 (Nudt2) is to hydrolyze the secondary messenger diadenosine 5', 5’’’-p1, p4-tetraphosphate (Ap4A). In this study we examined the role of Nudt2 in breast carcinoma through its expression in the human invasion ductal carcinoma tissues, and its functions in human triple negative breast cancer (TNBC) cell lines. A significantly high expression of Nudt2 in the human invasion ductal carcinoma tissues was observed in our study. Knockdown of Nudt2 in TNBC cell lines showed a significant reduction in cellular proliferation via the Ki67 marker, accompanied by G0/G1 phase cell cycle arrest. A significant reduction in the migration and invasion of Nudt2 knockdown TNBC cell lines was also observed. The effect of Nudt2 knockdown in the TNBC cell lines on tumorigenicity and anchorage-independent growth was assessed, where significant reductions in the Nudt2 knockdown TNBC cell lines were found. It can therefore be concluded that Nudt2 plays a significant role in promoting TNBC growth.
Dermatology practical & conceptual, Oct 28, 2021
Neuroendocrinology, 2017
Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues plays an i... more Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues plays an increasing role in the treatment of patients with inoperable or metastasised gatroenteropancreatic neuroendocrine tumours (GEP-NETs). 90 Y-DOTATOC and 177 Lu-DOTATATE are the most used radiopeptides for PRRT with comparable tumour response rates (about 15-35%). The side effects of this therapy are few and mild. However, amino acids should be used for kidney protection, especially during infusion of 90 Y-DOTATOC. Options to improve PRRT may include combinations of radioactive labelled somatostatin analogues and the use of radiosensitising drugs combined with PRRT. Other therapeutic applications of PRRT may include intra-arterial administration, neoadjuvant treatment and additional PRRT cycles in patients with progressive disease, who have benefited from initial therapy.
JACC: Cardiooncology, Sep 1, 2020
International Journal of Molecular Sciences, Mar 21, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
PubMed, May 1, 2007
Background: Infective endocarditis is a common disease with significant morbidity and mortality. ... more Background: Infective endocarditis is a common disease with significant morbidity and mortality. Objectives: To define clinical and echocardiographic parameters predicting morbidity and in-hospital mortality in patients with infective endocarditis hospitalized in a tertiary hospital from 1991 to 2000. Methods: All patients with definite infective endocarditis diagnosed according to the Duke criteria were included. We examined relevant clinical features that might influence outcome. Results: The study group comprised 100 consecutive patients, 77 with native valve and 23 with prosthetic valve endocarditis. The overall in-hospital mortality rate was 8%. There was a higher mortality in the PVE group compared to the NVE group (13% vs. 7%, P = 0.07). The mortality rate in each group, with or without surgery, was not significantly different. Clinical predictors of mortality were older age and hospital-acquired endocarditis. The presence of vegetations and their size were significant predictors of major embolic events and mortality. Staphylococcus aureus was a predictor of mortality (25% vs. 5%, P < 0.005) and abscess formation. Multivariate logistic analysis identified vegetation size and S. aureus as independent predictors of mortality. Conclusions: Mortality is higher in older hospitalized patients. S. aureus is associated with a poor outcome. Vegetation size is an independent predictor of embolic events and of a higher mortality.
Sarcoma, 2013
Angiosarcomas are aggressive tumors of vascular endothelial origin, occurring sporadically or in ... more Angiosarcomas are aggressive tumors of vascular endothelial origin, occurring sporadically or in association with prior radiotherapy. We compared clinicopathologic and biologic features of sporadic angiosarcomas (SA) and radiation-associated angiosarcomas (RAA). Methods. From a University of Michigan institutional database, 37 SA and 11 RAA were identified. Tissue microarrays were stained for p53, Ki-67, and hTERT. DNA was evaluated for TP53 and ATM mutations. Results. Mean latency between radiotherapy and diagnosis of RAA was 11.9 years: 6.7 years for breast RAA versus 20.9 years for nonbreast RAA (= 0.148). Survival after diagnosis did not significantly differ between SA and RAA (= 0.590). Patients with nonbreast RAA had shorter overall survival than patients with breast RAA (= 0.03). The majority of SA (86.5%) and RAA (77.8%) were classified as high-grade sarcomas (= 0.609). RAA were more likely to have well-defined vasoformative areas (55.6% versus 27%, = 0.127). Most breast SA were parenchymal in origin (80%), while most breast RAA were cutaneous in origin (80%). TMA analysis showed p53 overexpression in 25.7% of SA and 0% RAA, high Ki-67 in 35.3% of SA and 44.4% RAA, and hTERT expression in 100% of SA and RAA. TP53 mutations were detected in 13.5% of SA and 11.1% RAA. ATM mutations were not detected in either SA or RAA. Conclusions. SA and RAA are similar in histology, immunohistochemical markers, and DNA mutation profiles and share similar prognosis. Breast RAA have a shorter latency period compared to nonbreast RAA and a significantly longer survival.
Clinical Nuclear Medicine, 2017
Aim: Castrate-resistant prostate cancer (CRPC) often shows histological evidence of neuroendocrin... more Aim: Castrate-resistant prostate cancer (CRPC) often shows histological evidence of neuroendocrine differentiation (NED). To evaluate the extent of NED in patients with CRPC, we used PET/CTwith 68 Ga-[DOTA-Tyr 3 ]-octreotate (68 Ga-DOTA-TATE), a somatostatin analog that binds somatostatin receptor 2 with high affinity. This radiotracer is used in imaging of neuroendocrine tumors. Methods: Twelve patients (mean age, 65 [SD, 12] years) with CRPC were studied. Their mean prostate-specific antigen level at scanning was 85.6 (SD, 144.6) ng/mL. PET/CT images were obtained after the injection of 120 to 200 MBq of 68 Ga-DOTA-TATE. Results: All participants had at least 1 blastic metastasis demonstrating uptake of 68 Ga-DOTA-TATE (mean SUVmax of 5.3 [SD, 2.3]). In 6 patients, moderately high to high uptakes (SUVmax, >5) were seen. Patients with multiple bone metastases had a significantly higher SUVmax compared with patients with few metastases (mean of 5.8 vs 3.8, P = 0.05). In 4 patients, lytic bone lesions or lymph node metastases also showed uptake of the tracer (mean SUVmax of 7.2 [SD, 3.2]). Uptake of the radiotracer was also observed in bones showing normal architecture in CT, suggesting that NED cells appear early during metastases development. Conclusions: Uptake of 68 Ga-DOTA-TATE is a common finding in metastases of CRPC patients, suggesting that NED is frequent in these patients. In half of the patients, widespread uptake of 68 Ga-DOTA-TATE was observed. This suggests that the possibility of treating selected CRCP patients with anti-neuroendocrine tumor therapies should be explored and that 68 Ga-DOTA-TATE scanning could have a role in predicting the efficacy of these treatments.
Cancer Research, Mar 31, 2011
Pancreatic cancer is characterized by very low survival rates because of high intrinsic resistanc... more Pancreatic cancer is characterized by very low survival rates because of high intrinsic resistance to conventional therapies. Ionizing radiation (IR)-enhanced tumor invasiveness is emerging as one mechanism responsible for the limited benefit of radiotherapy in pancreatic cancer. In this study, we establish the role of heparanase-the only known mammalian endoglycosidase that cleaves heparan sulfate-in modulating the response of pancreatic cancer to radiotherapy. We found that clinically relevant doses of IR augment the invasive capability of pancreatic carcinoma cells in vitro and in vivo by upregulating heparanase. Changes in the levels of the transcription factor Egr-1 occurred in pancreatic cancer cells following radiation, underlying the stimulatory effect of IR on heparanase expression. Importantly, the specific heparanase inhibitor SST0001 abolished IR-enhanced invasiveness of pancreatic carcinoma cells in vitro, whereas combined treatment with SST0001 and IR, but not IR alone, attenuated the spread of orthotopic pancreatic tumors in vivo. Taken together, our results suggest that combining radiotherapy with heparanase inhibition is an effective strategy to prevent tumor resistance and dissemination, observed in many IR-treated pancreatic cancer patients. Further, the molecular mechanism underlying heparanase upregulation in pancreatic cancer that we identified in response to IR may help identify patients in which radiotherapeutic intervention may confer increased risk of metastatic spread, where antiheparanase therapy may be particularly beneficial. Cancer Res; 71(7); 2772-80. Ó2011 AACR.
The Journal of Clinical Endocrinology and Metabolism, Jun 9, 2017
Purpose: Treatment options for unresectable paraganglioma (PGL)/pheochromocytoma (PCC), especiall... more Purpose: Treatment options for unresectable paraganglioma (PGL)/pheochromocytoma (PCC), especially with uncontrolled secondary hypertension (HTN), are limited. Preliminary studies with peptide receptor radionuclide therapy (PRRT) suggest efficacy, but data on HTN control and survival are lacking. We assessed PRRT outcomes in such patients from two referral centers. Methods: Twenty consecutive patients (13 men; age range, 21 to 77 years) with high somatostatin receptor (SSTR) expression treated with 177 Lu-DOTA-octreotate, nine with radiosensitizing chemotherapy, were retrospectively reviewed. Median cumulative activity was 22 GBq (median 4 cycles). Fourteen patients were treated for uncontrolled HTN and six for progressive or symptomatic metastatic disease or local recurrence. Results: Three months after PRRT, 8 of 14 patients treated for HTN required reduced medication doses, 5 had no change in anti-HTN doses, and 1 was lost to follow-up. Eighty-six percent had serum chromogranin-A reduction. Of the entire cohort, 36% had disease regression (29% partial and 7% minor response) on computed tomography, with stable findings in 50%. Three other patients had bony disease evaluable only on SSTR imaging (2 partial response and 1 stable). Median progressionfree survival was 39 months; median overall survival was not reached (5 deaths; median follow-up, 28 months). Four patients had grade 3 lymphopenia; 2 had grade 3 thrombocytopenia. Renal impairment in 2 patients was attributed to underlying disease processes. Conclusions: PRRT achieves worthwhile clinical and biochemical responses with low toxicity and encouraging survival in PGL/PCC. Because PRRT has logistic and radiation-safety advantages compared to 131 I-MIBG therapy, further prospective evaluation is warranted.
International Journal of Radiation Oncology Biology Physics, Nov 1, 2022
Internal Medicine Journal, 2021
Internal Medicine Journal, Apr 1, 2017
Anticancer Research, Oct 26, 2022
Journal of Contemporary Brachytherapy, 2019
Primary sarcoma of the heart is a rare but devastating tumor. Median survival with conventional t... more Primary sarcoma of the heart is a rare but devastating tumor. Median survival with conventional treatment is 8-12 months. When resection is not feasible, patients often succumb to heart failure secondary to obstruction of blood flow, valve dysfunction, chamber compression or conduction abnormalities. Palliative treatment options include systemic chemotherapy and external beam irradiation. We herein describe a novel technique using endovascular brachytherapy, aiming at reducing tumor mass, alleviating right ventricular pressure overload and at the same time keeping the option of R0 resection viable. Material and methods: A 35-year-old man was diagnosed with a non-resectable high-grade intimal sarcoma of the right ventricle (RV), main pulmonary artery (PA) and right PA. After three cycles of doxorubicin and ifosfamide, the patient's symptoms of right heart failure worsened. Imaging documented tumor progression and supra-systemic pulmonary artery pressure. Through a trans-femoral venous access, a brachytherapy sleeve was placed in the RV and main and right PA. A dose of 20 Gy was delivered over a period of ten minutes. Results: The patient had an uneventful course and was discharged home 24 hours after the procedure. Ten months after brachytherapy, repeat imaging demonstrated a significant reduction in tumor volume and an increase in pulmonary artery cross-sectional area with a marked reduction of pulmonary artery pressure, leading to a complete resolution of heart failure symptoms. Conclusions: Endovascular brachytherapy is a novel, safe and effective therapeutic modality for non-resectable primary cardiac sarcomas either for palliation of obstruction, or tumor mass reduction to allow complete resection.
Anticancer Research, Oct 26, 2022
Background/Aim: Cancer progression is associated with significant cachexia-induced weight loss an... more Background/Aim: Cancer progression is associated with significant cachexia-induced weight loss and stomatitis. Pentoxifylline (PTX) is a drug shown to have beneficial antiinflammatory effects in cancer patients, mainly through anti-TNFα mechanisms. This study determined the PTX effects and mode of action on weight-loss, stomatitis, and survival in colon cancer patients treated with chemotherapy, examining the kinetics of tumor markers and cytokine levels. Patients and Methods: Forty patients with metastatic colon cancer receiving chemotherapy, were randomized in this study. Seventeen patients were assigned to the treatment group-8 received a full PTX dose (400 mg TID) and 9 a reduced dose (200 mg TID). Results were compared to 23 untreated, control patients. Blood analysis of tumor markers (CEA and TPS), inflammatory cytokines (IL-1β, IL-6, IL-8, TNFα, TNF-R), CRP and sIL-2R, were performed. Additionally, clinical parameters were assessed. Results: Patients treated with PTX (full/reduced doses), gained significant weight, and experienced a reduction in stomatitis, resulting in multiple beneficial effects, including improved life quality. Significant reductions in CRP, sIL-2R, and inflammatory cytokine levels, correlated to increases in weight and a reduction in stomatitis. A similar pattern was observed in tumor marker levels, where decreasing levels were correlated with weight gain and reduction in inflammatory cytokine levels. Conclusion: Colon cancer patients receiving PTX with chemotherapy, experienced weight gain and reduced stomatitis occurrence. Beneficial PTX effects were correlated to significant decreases in patient inflammatory cytokines and tumor marker levels, probably due to PTX mode of action. Cancer progression, especially in end-stage patients, is associated with cachexia-a complex metabolic syndrome characterized by a loss of muscle mass/ fat mass and reduced well-being and survival (1). While there are various treatment options for cancer cachexia, including cyproheptadine, hydrazine, and metoclopramide, none of these drugs has been found to be sufficiently effective. Pentoxifylline (PTX), anti-TNFα monoclonal antibody and selective COX-2 inhibitors, have been suggested as promising treatment options (1, 2). PTX, a xanthine derivative, has been shown to have a significant effect on the cellular mediators of inflammation and tissue injury. Cancer cachexia has been linked to elevated levels of inflammatory cytokines, mainly tumor necrosis factor-alpha (TNFα), but also IL-6 and IL-8 (3). PTX has been shown to inhibit TNFα production and therefore reduce cachexia parameters. In a randomized double-blind controlled clinical trial involving hemodialysis patients, PTX decreased TNFα, IL-6 and CRP serum levels (4). In another study, PTX was shown to decrease TLR-mediated TNFα mRNA while increasing IL-10 mRNA, an anti-inflammatory cytokine (3-5). PTX not only possesses direct anticancer activity by inducing both apoptosis and the sensitization of multi-drug resistant cells (6, 7) but also increases cancer cell susceptibility to radiation therapy, while reducing long-term radiation side effects. It has been reported that the combination of PTX and vitamin E (7) reduces the severity of radiation-induced oral mucositis and dysphagia in head and neck cancer patients (8, 9). In addition, it has been suggested that PTX reduces chemotherapy-induced stomatitis and osteonecrosis, through inflammatory cytokine reduction (8-12). We have previously reported on the significance of using tumor and cytokine markers in the clinical work-up of oncological patients, including the importance of tumor markers (TMs) in the early detection of recurrence and metastasis, such as in breast (13-16), colon (14), and head 5487
EJNMMI Physics, Feb 12, 2021
Background: Image quality and quantitative accuracy of positron emission tomography (PET) depend ... more Background: Image quality and quantitative accuracy of positron emission tomography (PET) depend on several factors such as uptake time, scanner characteristics and image reconstruction methods. Ordered subset expectation maximization (OSEM) is considered the gold standard for image reconstruction. Penalized-likelihood estimation (PL) algorithms have been recently developed for PET reconstruction to improve quantitation accuracy while maintaining or even improving image quality. In PL algorithms, a regularization parameter β controls the penalization of relative differences between neighboring pixels and determines image characteristics. In the present study, we aim to compare the performance of Q.Clear (PL algorithm, GE Healthcare) and OSEM (3 iterations, 8 subsets, 6-mm post-processing filter) for 68 Ga-DOTATATE (68 Ga-DOTA) PET studies, both visually and quantitatively. Thirty consecutive whole-body 68 Ga-DOTA studies were included. The data were acquired in list mode and were reconstructed using 3D OSEM and Q.Clear with various values of β and various acquisition times per bed position (bp), thus generating images with reduced injected dose (1.5 min/bp: β = 300-1100; 1.0 min/bp: β = 600-1400 and 0.5 min/bp: β = 800-2200). An additional analysis adding β values up to 1500, 1700 and 3000 for 1.5, 1.0 and 0.5 min/bp, respectively, was performed for a random sample of 8 studies. Evaluation was performed using a phantom and clinical data. Two experienced nuclear medicine physicians blinded to the variables assessed the image quality visually. Results: Clinical images reconstructed with Q.Clear, set at 1.5, 1.0 and 0.5 min/bp using β = 1100, 1300 and 3000, respectively, resulted in images with noise equivalence to 3D OSEM (1.5 min/bp) with a mean increase in SUV max of 14%, 13% and 4%, an increase in SNR of 30%, 24% and 10%, and an increase in SBR of 13%, 13% and 2%. Visual assessment yielded similar results for β values of 1100-1400 and 1300-1600 for 1.5 and 1.0 min/bp, respectively, although for 0.5 min/bp there was no significant improvement compared to OSEM. Conclusion: 68 Ga-DOTA reconstructions with Q.Clear, 1.5 and 1.0 min/bp, resulted in increased tumor SUV max and in improved SNR and SBR at a similar level of noise compared to 3D OSEM. Q.Clear with β = 1300-1600 enables one-third reduction of acquisition time or injected dose, with similar image quality compared to 3D OSEM.
Journal of Thoracic Oncology
Research Square (Research Square), Dec 11, 2020
Background: Image quality and quantitative accuracy of positron emission tomography (PET) depend ... more Background: Image quality and quantitative accuracy of positron emission tomography (PET) depend on several factors such as uptake time, scanner characteristics and image reconstruction methods. Ordered subset expectation maximization (OSEM) is considered the gold standard for image reconstruction. Penalized-likelihood estimation (PL) algorithms have been recently developed for PET reconstruction to improve quantitation accuracy while maintaining or even improving image quality. In PL algorithms, a regularization parameter β controls the penalization of relative differences between neighboring pixels and determines image characteristics. In the present study, we aim to compare the performance of Q.Clear (PL algorithm, GE Healthcare) and OSEM (3 iterations, 8 subsets, 6-mm post-processing filter) for 68 Ga-DOTATATE (68 Ga-DOTA) PET studies, both visually and quantitatively. Thirty consecutive whole-body 68 Ga-DOTA studies were included. The data were acquired in list mode and were reconstructed using 3D OSEM and Q.Clear with various values of β and various acquisition times per bed position (bp), thus generating images with reduced injected dose (1.5 min/bp: β = 300-1100; 1.0 min/bp: β = 600-1400 and 0.5 min/bp: β = 800-2200). An additional analysis adding β values up to 1500, 1700 and 3000 for 1.5, 1.0 and 0.5 min/bp, respectively, was performed for a random sample of 8 studies. Evaluation was performed using a phantom and clinical data. Two experienced nuclear medicine physicians blinded to the variables assessed the image quality visually. Results: Clinical images reconstructed with Q.Clear, set at 1.5, 1.0 and 0.5 min/bp using β = 1100, 1300 and 3000, respectively, resulted in images with noise equivalence to 3D OSEM (1.5 min/bp) with a mean increase in SUV max of 14%, 13% and 4%, an increase in SNR of 30%, 24% and 10%, and an increase in SBR of 13%, 13% and 2%. Visual assessment yielded similar results for β values of 1100-1400 and 1300-1600 for 1.5 and 1.0 min/bp, respectively, although for 0.5 min/bp there was no significant improvement compared to OSEM. Conclusion: 68 Ga-DOTA reconstructions with Q.Clear, 1.5 and 1.0 min/bp, resulted in increased tumor SUV max and in improved SNR and SBR at a similar level of noise compared to 3D OSEM. Q.Clear with β = 1300-1600 enables one-third reduction of acquisition time or injected dose, with similar image quality compared to 3D OSEM.
Harefuah, Jul 1, 2021
Aims: The aim of this study was to evaluate the predictive power of the absorbed dose to kidneys ... more Aims: The aim of this study was to evaluate the predictive power of the absorbed dose to kidneys after the first course of treatment with [177Lu]-DOTA-TATE on the cumulative kidney absorbed dose after 3 or 4 cycles of treatment. Background: Peptide receptor radionuclide therapy (PRRT) with [177Lu]-DOTA-TATE is an effective treatment for somatostatin receptor positive neuroendocrine tumors (NETs). Post-treatment scans (PTS) are required after each cycle of treatment for personalized radiation dosimetry in order to calculate the dose to organs and tumors and to ensure a cumulative absorbed dose to kidneys under a safety threshold of 25 Gy. Methods: A total of 187 patients who completed treatment and underwent PTS for dosimetry calculation were included in this retrospective study. The correlation between the cumulative absorbed dose to the kidneys after completion of treatment and the absorbed dose after the first cycle(s) was studied. Multilinear regression analysis was performed to predict the cumulative absorbed dose by the kidneys in the subsequent cycles. An algorithm for the follow-up of the kidney absorbed dose is proposed. Results: When the absorbed dose to kidneys after the first cycle of treatment is below 5.6 Gy, four cycles of treatment can be safely administered with a cumulative dose less than 25 Gy (p < 0.1). For the remaining patients, the cumulative dose absorbed after 3 or 4 cycles of treatment can be predicted after the second cycle of treatment. This protocol enabled early decisions on the number of treatment cycles and reduced the number of post-treatment SPECT/CT studies for dosimetry in 34% of patients, as well as hospitalization time for 56% of the treatment cycles. Conclusions: Assessment of the kidney absorbed dose after PRRT can be simplified with the algorithm presented in this study. This approach enabled early decisions on the number of therapy cycles in 75% of patients. Discussion: The validity of these results is limited to the protocol of dosimetry calculation used in our institution. Implementation in other centers may require standardization of the acquisition parameters and the dosimetry protocol.
The main known function of Nudix hydrolase 2 (Nudt2) is to hydrolyze the secondary messenger diad... more The main known function of Nudix hydrolase 2 (Nudt2) is to hydrolyze the secondary messenger diadenosine 5', 5’’’-p1, p4-tetraphosphate (Ap4A). In this study we examined the role of Nudt2 in breast carcinoma through its expression in the human invasion ductal carcinoma tissues, and its functions in human triple negative breast cancer (TNBC) cell lines. A significantly high expression of Nudt2 in the human invasion ductal carcinoma tissues was observed in our study. Knockdown of Nudt2 in TNBC cell lines showed a significant reduction in cellular proliferation via the Ki67 marker, accompanied by G0/G1 phase cell cycle arrest. A significant reduction in the migration and invasion of Nudt2 knockdown TNBC cell lines was also observed. The effect of Nudt2 knockdown in the TNBC cell lines on tumorigenicity and anchorage-independent growth was assessed, where significant reductions in the Nudt2 knockdown TNBC cell lines were found. It can therefore be concluded that Nudt2 plays a significant role in promoting TNBC growth.
Dermatology practical & conceptual, Oct 28, 2021
Neuroendocrinology, 2017
Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues plays an i... more Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues plays an increasing role in the treatment of patients with inoperable or metastasised gatroenteropancreatic neuroendocrine tumours (GEP-NETs). 90 Y-DOTATOC and 177 Lu-DOTATATE are the most used radiopeptides for PRRT with comparable tumour response rates (about 15-35%). The side effects of this therapy are few and mild. However, amino acids should be used for kidney protection, especially during infusion of 90 Y-DOTATOC. Options to improve PRRT may include combinations of radioactive labelled somatostatin analogues and the use of radiosensitising drugs combined with PRRT. Other therapeutic applications of PRRT may include intra-arterial administration, neoadjuvant treatment and additional PRRT cycles in patients with progressive disease, who have benefited from initial therapy.
JACC: Cardiooncology, Sep 1, 2020
International Journal of Molecular Sciences, Mar 21, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
PubMed, May 1, 2007
Background: Infective endocarditis is a common disease with significant morbidity and mortality. ... more Background: Infective endocarditis is a common disease with significant morbidity and mortality. Objectives: To define clinical and echocardiographic parameters predicting morbidity and in-hospital mortality in patients with infective endocarditis hospitalized in a tertiary hospital from 1991 to 2000. Methods: All patients with definite infective endocarditis diagnosed according to the Duke criteria were included. We examined relevant clinical features that might influence outcome. Results: The study group comprised 100 consecutive patients, 77 with native valve and 23 with prosthetic valve endocarditis. The overall in-hospital mortality rate was 8%. There was a higher mortality in the PVE group compared to the NVE group (13% vs. 7%, P = 0.07). The mortality rate in each group, with or without surgery, was not significantly different. Clinical predictors of mortality were older age and hospital-acquired endocarditis. The presence of vegetations and their size were significant predictors of major embolic events and mortality. Staphylococcus aureus was a predictor of mortality (25% vs. 5%, P < 0.005) and abscess formation. Multivariate logistic analysis identified vegetation size and S. aureus as independent predictors of mortality. Conclusions: Mortality is higher in older hospitalized patients. S. aureus is associated with a poor outcome. Vegetation size is an independent predictor of embolic events and of a higher mortality.
Sarcoma, 2013
Angiosarcomas are aggressive tumors of vascular endothelial origin, occurring sporadically or in ... more Angiosarcomas are aggressive tumors of vascular endothelial origin, occurring sporadically or in association with prior radiotherapy. We compared clinicopathologic and biologic features of sporadic angiosarcomas (SA) and radiation-associated angiosarcomas (RAA). Methods. From a University of Michigan institutional database, 37 SA and 11 RAA were identified. Tissue microarrays were stained for p53, Ki-67, and hTERT. DNA was evaluated for TP53 and ATM mutations. Results. Mean latency between radiotherapy and diagnosis of RAA was 11.9 years: 6.7 years for breast RAA versus 20.9 years for nonbreast RAA (= 0.148). Survival after diagnosis did not significantly differ between SA and RAA (= 0.590). Patients with nonbreast RAA had shorter overall survival than patients with breast RAA (= 0.03). The majority of SA (86.5%) and RAA (77.8%) were classified as high-grade sarcomas (= 0.609). RAA were more likely to have well-defined vasoformative areas (55.6% versus 27%, = 0.127). Most breast SA were parenchymal in origin (80%), while most breast RAA were cutaneous in origin (80%). TMA analysis showed p53 overexpression in 25.7% of SA and 0% RAA, high Ki-67 in 35.3% of SA and 44.4% RAA, and hTERT expression in 100% of SA and RAA. TP53 mutations were detected in 13.5% of SA and 11.1% RAA. ATM mutations were not detected in either SA or RAA. Conclusions. SA and RAA are similar in histology, immunohistochemical markers, and DNA mutation profiles and share similar prognosis. Breast RAA have a shorter latency period compared to nonbreast RAA and a significantly longer survival.
Clinical Nuclear Medicine, 2017
Aim: Castrate-resistant prostate cancer (CRPC) often shows histological evidence of neuroendocrin... more Aim: Castrate-resistant prostate cancer (CRPC) often shows histological evidence of neuroendocrine differentiation (NED). To evaluate the extent of NED in patients with CRPC, we used PET/CTwith 68 Ga-[DOTA-Tyr 3 ]-octreotate (68 Ga-DOTA-TATE), a somatostatin analog that binds somatostatin receptor 2 with high affinity. This radiotracer is used in imaging of neuroendocrine tumors. Methods: Twelve patients (mean age, 65 [SD, 12] years) with CRPC were studied. Their mean prostate-specific antigen level at scanning was 85.6 (SD, 144.6) ng/mL. PET/CT images were obtained after the injection of 120 to 200 MBq of 68 Ga-DOTA-TATE. Results: All participants had at least 1 blastic metastasis demonstrating uptake of 68 Ga-DOTA-TATE (mean SUVmax of 5.3 [SD, 2.3]). In 6 patients, moderately high to high uptakes (SUVmax, >5) were seen. Patients with multiple bone metastases had a significantly higher SUVmax compared with patients with few metastases (mean of 5.8 vs 3.8, P = 0.05). In 4 patients, lytic bone lesions or lymph node metastases also showed uptake of the tracer (mean SUVmax of 7.2 [SD, 3.2]). Uptake of the radiotracer was also observed in bones showing normal architecture in CT, suggesting that NED cells appear early during metastases development. Conclusions: Uptake of 68 Ga-DOTA-TATE is a common finding in metastases of CRPC patients, suggesting that NED is frequent in these patients. In half of the patients, widespread uptake of 68 Ga-DOTA-TATE was observed. This suggests that the possibility of treating selected CRCP patients with anti-neuroendocrine tumor therapies should be explored and that 68 Ga-DOTA-TATE scanning could have a role in predicting the efficacy of these treatments.
Cancer Research, Mar 31, 2011
Pancreatic cancer is characterized by very low survival rates because of high intrinsic resistanc... more Pancreatic cancer is characterized by very low survival rates because of high intrinsic resistance to conventional therapies. Ionizing radiation (IR)-enhanced tumor invasiveness is emerging as one mechanism responsible for the limited benefit of radiotherapy in pancreatic cancer. In this study, we establish the role of heparanase-the only known mammalian endoglycosidase that cleaves heparan sulfate-in modulating the response of pancreatic cancer to radiotherapy. We found that clinically relevant doses of IR augment the invasive capability of pancreatic carcinoma cells in vitro and in vivo by upregulating heparanase. Changes in the levels of the transcription factor Egr-1 occurred in pancreatic cancer cells following radiation, underlying the stimulatory effect of IR on heparanase expression. Importantly, the specific heparanase inhibitor SST0001 abolished IR-enhanced invasiveness of pancreatic carcinoma cells in vitro, whereas combined treatment with SST0001 and IR, but not IR alone, attenuated the spread of orthotopic pancreatic tumors in vivo. Taken together, our results suggest that combining radiotherapy with heparanase inhibition is an effective strategy to prevent tumor resistance and dissemination, observed in many IR-treated pancreatic cancer patients. Further, the molecular mechanism underlying heparanase upregulation in pancreatic cancer that we identified in response to IR may help identify patients in which radiotherapeutic intervention may confer increased risk of metastatic spread, where antiheparanase therapy may be particularly beneficial. Cancer Res; 71(7); 2772-80. Ó2011 AACR.
The Journal of Clinical Endocrinology and Metabolism, Jun 9, 2017
Purpose: Treatment options for unresectable paraganglioma (PGL)/pheochromocytoma (PCC), especiall... more Purpose: Treatment options for unresectable paraganglioma (PGL)/pheochromocytoma (PCC), especially with uncontrolled secondary hypertension (HTN), are limited. Preliminary studies with peptide receptor radionuclide therapy (PRRT) suggest efficacy, but data on HTN control and survival are lacking. We assessed PRRT outcomes in such patients from two referral centers. Methods: Twenty consecutive patients (13 men; age range, 21 to 77 years) with high somatostatin receptor (SSTR) expression treated with 177 Lu-DOTA-octreotate, nine with radiosensitizing chemotherapy, were retrospectively reviewed. Median cumulative activity was 22 GBq (median 4 cycles). Fourteen patients were treated for uncontrolled HTN and six for progressive or symptomatic metastatic disease or local recurrence. Results: Three months after PRRT, 8 of 14 patients treated for HTN required reduced medication doses, 5 had no change in anti-HTN doses, and 1 was lost to follow-up. Eighty-six percent had serum chromogranin-A reduction. Of the entire cohort, 36% had disease regression (29% partial and 7% minor response) on computed tomography, with stable findings in 50%. Three other patients had bony disease evaluable only on SSTR imaging (2 partial response and 1 stable). Median progressionfree survival was 39 months; median overall survival was not reached (5 deaths; median follow-up, 28 months). Four patients had grade 3 lymphopenia; 2 had grade 3 thrombocytopenia. Renal impairment in 2 patients was attributed to underlying disease processes. Conclusions: PRRT achieves worthwhile clinical and biochemical responses with low toxicity and encouraging survival in PGL/PCC. Because PRRT has logistic and radiation-safety advantages compared to 131 I-MIBG therapy, further prospective evaluation is warranted.
International Journal of Radiation Oncology Biology Physics, Nov 1, 2022
Internal Medicine Journal, 2021
Internal Medicine Journal, Apr 1, 2017
Anticancer Research, Oct 26, 2022
Journal of Contemporary Brachytherapy, 2019
Primary sarcoma of the heart is a rare but devastating tumor. Median survival with conventional t... more Primary sarcoma of the heart is a rare but devastating tumor. Median survival with conventional treatment is 8-12 months. When resection is not feasible, patients often succumb to heart failure secondary to obstruction of blood flow, valve dysfunction, chamber compression or conduction abnormalities. Palliative treatment options include systemic chemotherapy and external beam irradiation. We herein describe a novel technique using endovascular brachytherapy, aiming at reducing tumor mass, alleviating right ventricular pressure overload and at the same time keeping the option of R0 resection viable. Material and methods: A 35-year-old man was diagnosed with a non-resectable high-grade intimal sarcoma of the right ventricle (RV), main pulmonary artery (PA) and right PA. After three cycles of doxorubicin and ifosfamide, the patient's symptoms of right heart failure worsened. Imaging documented tumor progression and supra-systemic pulmonary artery pressure. Through a trans-femoral venous access, a brachytherapy sleeve was placed in the RV and main and right PA. A dose of 20 Gy was delivered over a period of ten minutes. Results: The patient had an uneventful course and was discharged home 24 hours after the procedure. Ten months after brachytherapy, repeat imaging demonstrated a significant reduction in tumor volume and an increase in pulmonary artery cross-sectional area with a marked reduction of pulmonary artery pressure, leading to a complete resolution of heart failure symptoms. Conclusions: Endovascular brachytherapy is a novel, safe and effective therapeutic modality for non-resectable primary cardiac sarcomas either for palliation of obstruction, or tumor mass reduction to allow complete resection.
Anticancer Research, Oct 26, 2022
Background/Aim: Cancer progression is associated with significant cachexia-induced weight loss an... more Background/Aim: Cancer progression is associated with significant cachexia-induced weight loss and stomatitis. Pentoxifylline (PTX) is a drug shown to have beneficial antiinflammatory effects in cancer patients, mainly through anti-TNFα mechanisms. This study determined the PTX effects and mode of action on weight-loss, stomatitis, and survival in colon cancer patients treated with chemotherapy, examining the kinetics of tumor markers and cytokine levels. Patients and Methods: Forty patients with metastatic colon cancer receiving chemotherapy, were randomized in this study. Seventeen patients were assigned to the treatment group-8 received a full PTX dose (400 mg TID) and 9 a reduced dose (200 mg TID). Results were compared to 23 untreated, control patients. Blood analysis of tumor markers (CEA and TPS), inflammatory cytokines (IL-1β, IL-6, IL-8, TNFα, TNF-R), CRP and sIL-2R, were performed. Additionally, clinical parameters were assessed. Results: Patients treated with PTX (full/reduced doses), gained significant weight, and experienced a reduction in stomatitis, resulting in multiple beneficial effects, including improved life quality. Significant reductions in CRP, sIL-2R, and inflammatory cytokine levels, correlated to increases in weight and a reduction in stomatitis. A similar pattern was observed in tumor marker levels, where decreasing levels were correlated with weight gain and reduction in inflammatory cytokine levels. Conclusion: Colon cancer patients receiving PTX with chemotherapy, experienced weight gain and reduced stomatitis occurrence. Beneficial PTX effects were correlated to significant decreases in patient inflammatory cytokines and tumor marker levels, probably due to PTX mode of action. Cancer progression, especially in end-stage patients, is associated with cachexia-a complex metabolic syndrome characterized by a loss of muscle mass/ fat mass and reduced well-being and survival (1). While there are various treatment options for cancer cachexia, including cyproheptadine, hydrazine, and metoclopramide, none of these drugs has been found to be sufficiently effective. Pentoxifylline (PTX), anti-TNFα monoclonal antibody and selective COX-2 inhibitors, have been suggested as promising treatment options (1, 2). PTX, a xanthine derivative, has been shown to have a significant effect on the cellular mediators of inflammation and tissue injury. Cancer cachexia has been linked to elevated levels of inflammatory cytokines, mainly tumor necrosis factor-alpha (TNFα), but also IL-6 and IL-8 (3). PTX has been shown to inhibit TNFα production and therefore reduce cachexia parameters. In a randomized double-blind controlled clinical trial involving hemodialysis patients, PTX decreased TNFα, IL-6 and CRP serum levels (4). In another study, PTX was shown to decrease TLR-mediated TNFα mRNA while increasing IL-10 mRNA, an anti-inflammatory cytokine (3-5). PTX not only possesses direct anticancer activity by inducing both apoptosis and the sensitization of multi-drug resistant cells (6, 7) but also increases cancer cell susceptibility to radiation therapy, while reducing long-term radiation side effects. It has been reported that the combination of PTX and vitamin E (7) reduces the severity of radiation-induced oral mucositis and dysphagia in head and neck cancer patients (8, 9). In addition, it has been suggested that PTX reduces chemotherapy-induced stomatitis and osteonecrosis, through inflammatory cytokine reduction (8-12). We have previously reported on the significance of using tumor and cytokine markers in the clinical work-up of oncological patients, including the importance of tumor markers (TMs) in the early detection of recurrence and metastasis, such as in breast (13-16), colon (14), and head 5487