Proposal on the use of Xenon-133 against COVID-19.

Since we are able to bring ionizing radiation in the form of a gas cloud to the respiratory system, we have wondered whether Xenon-133 inhalation could be exploited as a treatment option against Covid-19 respiratory virus infections, and urge colleagues in the scientific research community who have the capability to do so to explore the merits of using Xenon-133 in this way to determine whether its usefulness against the Covid-19 virus is indeed genuine.

Preoperative SPECT imaging as a tool for surgical planning in patients with axial neck and back pain.

OBJECTIVE: Hybrid SPECT with CT imaging has been used to help elucidate pain generators in patients with axial neck and back pain, identifying potential sites for treatment. Few studies have examined its role in spine surgery and most literature focuses on its use postoperatively. The authors describe the largest series to date of patients with symptomatic spondylosis who underwent preoperative SPECT imaging for surgical planning. METHODS: A retrospective medical and imaging record review was conducted to identify patients who underwent SPECT or SPECT/CT studies between January 2014 and May 2018. Patients who underwent spine surgical intervention for spondylosis with primary symptoms of axial neck or back pain and who had evidence of hypermetabolic foci on spinal SPECT imaging were included. Only those patients who subsequently underwent surgery on a spinal level associated with increased radiotracer uptake were included in the analysis. Patient baseline and demographic information, and data pertaining to SPECT imaging, surgical planning, and postoperative care were collected and analyzed. RESULTS: A total of 23 patients with an average age at surgery of 60.0 ± 11.0 years were included. Fifteen patients (65.2%) were male. A total of 53 spinal levels were treated, with an average of 2.30 levels treated per patient. All patients underwent fusion surgery, either lumbar (n = 14), with interbody fusion most commonly used (64.2%); or cervical (n = 9), with anterior cervical discectomy and fusion (66.6%) being the most common. The average length of hospital stay was 3.45 ± 2.32 days. One patient developed a wound infection postoperatively, requiring readmission. At the 3-month follow-up, 18 patients (78.3%) reported clinical improvement in pain. Eleven patients (47.8%) reported complete symptom resolution at the 6-month follow-up. At 1 year postoperatively, 19 patients (82.6%) reported significant relief of their symptoms following surgery. CONCLUSIONS: This is the largest series to date describing patients with axial neck and back pain who underwent preoperative SPECT imaging and subsequent surgical intervention on the affected spinal levels. The results demonstrate that SPECT imaging may be a useful adjunct to guide surgical planning, resulting in substantial clinical improvement following surgery.

Fractionated radioimmunotherapy with (90) Y-clivatuzumab tetraxetan and low-dose gemcitabine is active in advanced pancreatic cancer: A phase 1 trial.

BACKGROUND: It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 ((90) Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease. METHODS: Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m(2) weekly for 4 weeks with (90) Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2-4). In the first part of the study, 19 patients received escalating weekly (90) Y doses of 6.5 mCi/m(2) , 9.0 mCi/m(2) , 12.0 mCi/m(2) , and 15.0 mCi/m(2) . In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m(2) or 12.0 mCi/m(2) . RESULTS: Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute's Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy. The maximum tolerated dose of (90) Y-hPAM4 was 12.0 mCi/m(2) weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m(2) weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at the higher radioimmunotherapy doses. CONCLUSIONS: Fractionated radioimmunotherapy with (90) Y-hPAM4 and low-dose gemcitabine demonstrated promising therapeutic activity and manageable myelosuppression in patients with advanced pancreatic ductal carcinoma.

Utility of positron emission tomography scans in mantle cell lymphoma.

Positron emission tomography (PET) scans are widely used in patients with lymphoma but little is known about their utility in mantle cell lymphoma (MCL). MCL patients were included from two prospective trials and one observational study at our institution. A total of 276 PET scans were performed among 52 patients. After a median follow-up of 37.5 months, the 3-year event-free survival (EFS) and overall survival (OS) were 73% (95% confidence interval [CI]: 61-85%) and 92% (95% CI 85-100%), respectively. There were 34 pretreatment PET scans, 26 interim, 28 end-of-treatment, 162 surveillance, and 26 scans at relapse or beyond. Pretreatment PETs were positive in 94%. A negative interim or end-of-therapy PET scan was not significantly associated with better EFS or OS, but no deaths were observed in patients who had a negative interim or end-of-therapy PET. Surveillance PET scans had a high false positive rate (35%) and low positive predictive value (8%). PET scans contributed to an earlier diagnosis of relapse in only two out of the 18 patients (11%) who relapsed. PET scans did not meaningfully contribute to staging or surveillance of MCL patients in this study. There was a trend toward improved survival in patients who had a negative end-of-therapy PET scan.

Radiopharmaceuticals: when and how to use them to treat metastatic bone pain.

Bone pain due to skeletal metastases constitutes the most common type of cancer-related pain. The management of bone pain remains challenging and is not standardized. In patients with multifocal osteoblastic metastases, systemic radiopharmaceuticals should be the preferred adjunctive therapy for pain palliation. The lack of general knowledge about radiopharmaceuticals, their clinical utility and safety profiles, constitutes the major cause for their underutilization. Our goal is to review the indications, selection criteria, efficacy, and toxicities of two approved radiopharmaceuticals for bone pain palliation: strontium-89 and samarium-153. Finally, a brief review of the data on combination therapy with bisphosphonates or chemotherapy is included.

FDG PET/CT of extranodal involvement in non-Hodgkin lymphoma and Hodgkin disease.

The term extranodal disease refers to lymphomatous infiltration of anatomic sites other than the lymph nodes. Almost any organ can be affected by lymphoma, with the most common extranodal sites of involvement being the stomach, spleen, Waldeyer ring, central nervous system, lung, bone, and skin. The prevalence of extranodal involvement in non-Hodgkin lymphoma and Hodgkin disease has increased in the past decade. The imaging characteristics of extranodal involvement can be subtle or absent at conventional computed tomography (CT). Imaging of tumor metabolism with 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) has facilitated the identification of affected extranodal sites, even when CT has demonstrated no lesions. More recently, hybrid PET/CT has become the standard imaging modality for initial staging, follow-up, and treatment response assessment in patients with lymphoma and has proved superior to CT in these settings. Certain PET/CT patterns are suggestive of extranodal disease and can help differentiate tumor from normal physiologic FDG activity, particularly in the mucosal tissues, bone marrow, and organs of the gastrointestinal tract. Familiarity with the different extranodal manifestations in various locations is critical for correct image interpretation. In addition, a knowledge of the differences in FDG avidity among the histologic subtypes of lymphoma, appropriate timing of scanning after therapeutic interventions, and use of techniques to prevent brown fat uptake are essential for providing the oncologist with accurate information.

Use of Single-Photon Emission Computed Tomography Imaging for Hypermetabolic Facet Identification in Diagnosis of Cervical and Axial Back Pain.

BACKGROUND: Few studies have used hybrid single-photon emission computed tomography (SPECT)/computed tomography (CT) scan to identify degenerative facet disease. We aimed to determine the incidence of hypermetabolic facets on SPECT/CT imaging in patients with axial neck or back pain to elucidate the value of SPECT/CT scan in identifying pain generators. METHODS: A retrospective review of adult patients with axial neck or back pain was conducted. A total of 190 patients underwent high-resolution SPECT/CT imaging using a standardized protocol from January 2010 to April 2018. Facet joints with increased radionuclide uptake on SPECT imaging were characterized as hypermetabolic. Number, level, and laterality of hypermetabolic facets were recorded based on review of imaging and radiologist impressions. RESULTS: The average age of the patients was 58 ± 13 years, and 51% of patients were men. A total of 85 patients (48%) demonstrated zygapophyseal joint hypermetabolism (ZJH) on SPECT imaging. A total of 202 hypermetabolic facets were identified, indicating the average number of facets with ZJH was 2.38 ± 1.91. Of patients with a positive scan, lumbar facets were most commonly affected (69% of ZJH) followed by cervical (24%) and thoracic regions (6%). C1-2 and C2-3 (22% each of cervical ZJH) and L4-5 (32% of lumbar ZJH) were most commonly affected in the cervical and lumbar regions, respectively. CONCLUSIONS: Nearly half of all patients with axial neck or back pain demonstrated ZJH on SPECT/CT imaging, supporting ZJH sites as potential pain generators and targets for treatment. Our results support the role for SPECT/CT imaging in the workup of patients with axial neck or back pain, which may reduce invasive diagnostic procedures and aid in treatment planning.

Usefulness of 123I-MIBG scintigraphy in the evaluation of patients with known or suspected primary or metastatic pheochromocytoma or paraganglioma: results from a prospective multicenter trial.

UNLABELLED: Although (123)I-MIBG has been in clinical use for the imaging of pheochromocytoma for many years, a large multicenter evaluation of this agent has never been performed. The present study was designed to provide a prospective confirmation of the performance of (123)I-MIBG scintigraphy for the evaluation of patients with known or suspected primary or metastatic pheochromocytoma or paraganglioma. METHODS: A total of 81 patients with a prior history of primary or metastatic pheochromocytoma or paraganglioma and 69 with suspected pheochromocytoma or paraganglioma based on symptoms of catecholamine excess, CT or MRI findings, or elevated catecholamine or metanephrine levels underwent whole-body planar and selected SPECT 24 h after the administration of (123)I-MIBG. Images were independently interpreted by 3 masked readers, with consensus requiring agreement of at least 2 readers. Final diagnoses were based on histopathology, correlative imaging, catecholamine or metanephrine measurements, and clinical follow-up. RESULTS: Among 140 patients with definitive diagnoses (91, disease present; 49, disease absent), (123)I-MIBG planar scintigraphy had a sensitivity and specificity of 82%. For patients evaluated for suspected disease, sensitivity and specificity were 88% and 84%, respectively. For the subpopulations of adrenal (pheochromocytoma) and extraadrenal (paraganglioma) tumors, sensitivities were 88% and 67%, respectively. The addition of SPECT increased reader confidence but minimally affected sensitivity and specificity. CONCLUSION: This prospective study demonstrated a sensitivity of 82%-88% and specificity of 82%-84% for (123)I-MIBG imaging used in the diagnostic assessment of primary or metastatic pheochromocytoma or paraganglioma.

Efficacy and Safety of High-Specific-Activity 131I-MIBG Therapy in Patients with Advanced Pheochromocytoma or Paraganglioma.

Patients with metastatic or unresectable (advanced) pheochromocytoma and paraganglioma (PPGL) have poor prognoses and few treatment options. This multicenter, phase 2 trial evaluated the efficacy and safety of high-specific-activity 131I-meta-iodobenzylguanidine (HSA 131I-MIBG) in patients with advanced PPGL. Methods: In this open-label, single-arm study, 81 PPGL patients were screened for enrollment, and 74 received a treatment-planning dose of HSA 131I-MIBG. Of these patients, 68 received at least 1 therapeutic dose (∼18.5 GBq) of HSA 131I-MIBG intravenously. The primary endpoint was the proportion of patients with at least a 50% reduction in baseline antihypertensive medication use lasting at least 6 mo. Secondary endpoints included objective tumor response as assessed by Response Evaluation Criteria in Solid Tumors version 1.0, biochemical tumor marker response, overall survival, and safety. Results: Of the 68 patients who received at least 1 therapeutic dose of HSA 131I-MIBG, 17 (25%; 95% confidence interval, 16%-37%) had a durable reduction in baseline antihypertensive medication use. Among 64 patients with evaluable disease, 59 (92%) had a partial response or stable disease as the best objective response within 12 mo. Decreases in elevated (≥1.5 times the upper limit of normal at baseline) serum chromogranin levels were observed, with confirmed complete and partial responses 12 mo after treatment in 19 of 28 patients (68%). The median overall survival was 36.7 mo (95% confidence interval, 29.9-49.1 mo). The most common treatment-emergent adverse events were nausea, myelosuppression, and fatigue. No patients had drug-related acute hypertensive events during or after the administration of HSA 131I-MIBG. Conclusion: HSA 131I-MIBG offers multiple benefits, including sustained blood pressure control and tumor response in PPGL patients.

Phase II study of (90)Y Ibritumomab tiuxetan (Zevalin) in patients with previously untreated marginal zone lymphoma.

The best upfront therapy for patients with non-gastric extranodal marginal zone lymphomas (MZLs) is not defined. We assessed the safety and efficacy of radioimmunotherapy with (90)yttrium ((90)Y) ibritumomab tiuxetan as upfront therapy in MZL (NCT00453102). A total of 16 patients were enrolled, 81% with advanced-stage disease and 44% with bulky disease. The overall response rate (ORR) at 12 weeks post-therapy was 87.5% (90% confidence interval [CI]: 65.6-97.7%), including a complete response in eight (50%), complete response unconfirmed in one (6%) and partial response in five (31%) patients. With a median follow-up of 65.6 months (range 4.0-96.5), the median progression-free survival (PFS) was 47.6 months (range 4.0-93.3) and median overall survival (OS) was not reached. The 5-year PFS was 40% (90% CI: 19.9-59.5%) and 5-year OS was 71.8% (90% CI: 46.8-86.5%). Overall, (90)Y ibritumomab tiuxetan was well tolerated and led to long-term responses and PFS rates.

Somatostatin receptor scintigraphy in MALT lymphoma of the lacrimal gland treated with rituximab.

Non-gastric stage I extranodal marginal zone lymphomas of MALT are usually treated with local therapy. However, distant relapses in other extranodal sites are not uncommon suggesting under-staging of these patients using conventional image studies. Positron emission tomography (PET) scans are frequently negative in this subgroup of patients with lymphoma and therefore do not significantly contribute to the staging process. We present a case of lacrimal gland MALT lymphoma demonstrating the usefulness of somatostatin receptor scintigraphy for initial staging and evaluation of response to treatment.

Protocol for the combined diagnostic and therapeutic use of recombinant human thyroid-stimulating hormone.

Patients may be prepared for radioiodine diagnostic imaging by withdrawal of all thyroid medication or by the administration of extrinsic thyroid-stimulating hormone (TSH). Although purified human and bovine TSHs were used in the past, they are no longer recommended because of their adverse effects. Recently, a new extrinsic TSH called recombinant human TSH (rhTSH) was developed and is commercially available. It is a highly purified, recombinant form of the naturally occurring human TSH. It was introduced to decrease complications associated with temporary hypothyroid states required at times in the follow-up evaluation of patients with thyroid cancer. Although rhTSH is currently used for patient preparation in diagnosis only, its use in preparations for subsequent radioiodine therapy may be helpful in some clinical circumstances. The authors describe a patient with papillary thyroid cancer in whom a 2-day rhTSH protocol was used for diagnosis and extended for therapeutic purposes. The protocol was useful to obtain the diagnostic information needed to determine whether to treat, and it allowed rapid progress to therapy without further patient preparation. Until rhTSH is fully approved for both diagnostic and therapeutic uses, this modified 2-day protocol would allow patients with special clinical circumstances to be evaluated and treated rapidly.

Systemic metabolic radiopharmaceutical therapy in the treatment of metastatic bone pain.

Bone pain due to skeletal metastases constitutes the most common type of chronic pain among patients with cancer. It significantly decreases the patient's quality of life and is associated with comorbidities, such as hypercalcemia, pathologic fractures and spinal cord compression. Approximately 65% of patients with prostate or breast cancer and 35% of those with advanced lung, thyroid, and kidney cancers will have symptomatic skeletal metastases. The management of bone pain is extremely difficult and involves a multidisciplinary approach, which usually includes analgesics, hormone therapies, bisphosphonates, external beam radiation, and systemic radiopharmaceuticals. In patients with extensive osseous metastases, systemic radiopharmaceuticals should be the preferred adjunctive therapy for pain palliation. In this article, we review the current approved radiopharmaceutical armamentarium for bone pain palliation, focusing on indications, patient selection, efficacy, and different biochemical characteristics and toxicity of strontium-89 chloride, samarium-153 lexidronam, and rhenium-186 etidronate. A brief discussion on the available data on rhenium-188 is presented focusing on its major advantages and disadvantages. We also perform a concise appraisal of the other available treatment options, including pharmacologic and hormonal treatment modalities, external beam radiation, and bisphosphonates. Finally, the available data on combination therapy of radiopharmaceuticals with bisphosphonates or chemotherapy are discussed.