Ga-68 DOTATATE PET/CT in the Evaluation of Paragangliomas and Other Indeterminate Lesions in the Head and Neck.

Background and Purpose: Paragangliomas (PGLs) are rare neuroendocrine tumors with imaging features that can overlap with other entities. This study hypothesizes that given overexpression of somatostatin receptor (SSTR) 2, PGLs can be differentiated on Ga-68 DOTATATE positron emission tomography/computed tomography (PET/CT) from other benign or malignant lesions. Materials and Methods: Ninety-six patients with known tumors of the head and neck who underwent Ga-68 DOTATATE PET/CT from May 2017 to December 2021 were retrospectively reviewed from a single institution. Of these, 43 patients had histopathological confirmation and 66 positive lesions were discovered on PET/CT. For each lesion, the SUV max, the SUV lesion to liver ratio, and the SUV lesion to spleen ratio were analyzed. Results: PGLs (n = 37) showed the most intense uptake, and the mean of SUVmax was 69.3 (range 3.7-225.9). Metastatic PGL and metastasis from other neuroendocrine tumors (n = 13) demonstrated intermediate uptake, the mean of SUVmax was 15.16 (range 2.3-40.3). Meningiomas (n = 3) had intermediate uptake, and the mean of SUVmax was 12.37 (range 2.5-19.4). One patient with esthesioneuroblastoma had 5 lesions in the head and neck, and the mean of SUVmax was 18.9 (range 6.9-49.4). Schwannomas (n = 4) had very low uptake, and the mean of SUVmax was 1.75 (range 1.1-2.2). Other rare cases with low uptake included 1 each of osteosarcoma, acinic cell carcinoma, ectopic thyroid tissue, and plasmacytoma, and the mean of SUVmax was 4.75 (range 2.3-6.1). Conclusions: Ga-68 DOTATATE PET/CT can be a useful adjunct in differentiating tumors in the head and neck. PGLs demonstrate the highest uptake. Meningioma, esthesioneuroblastoma, and neuroendocrine tumor metastasis have intermediate uptake. Schwannomas and other rare tumors exhibit low uptake.

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.

223Ra-Dichloride Response Evaluation Using 18F-Fluciclovine PET/CT and Bone Scintigraphy in a Patient With Castration-Resistant Metastatic Prostate Cancer.

A 66-year-old man was diagnosed with metastatic prostate cancer to the bones. The patient started Ra-dichloride (Xofigo) therapy in April 2019. Tc-MDP bone scan and F-fluciclovine (Axumin) PET/CT showed discordant but overall complementary findings that indicated disease progression after 5 doses of Xofigo therapy. The patient's prostate-specific antigen increased from 33.81 ng/mL at baseline before Xofigo therapy and up to 394.3 ng/mL after the fifth dose of Xofigo treatment. Because of disease progression, Xofigo therapy was discontinued.

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.

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.

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.

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.

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.

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.

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.

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.

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.

[18F]-fluorodeoxyglucose positron emission tomography combined with computed tomography detection of asymptomatic late pulmonary toxicity in patients with non-Hodgkin lymphoma treated with rituximab-containing chemotherapy.

Rituximab is a chimeric anti-CD20 monoclonal antibody widely used in the treatment of B-cell non-Hodgkin lymphomas (NHL). Most adverse effects are due to infusion-related reactions, and severe respiratory complications are rare. We retrospectively reviewed clinical data and serial imaging studies of five patients with NHL treated with rituximab-containing chemotherapy who developed new pulmonary abnormalities on routine follow-up FDG-PET/CT imaging. None of the patients had pulmonary lymphoma or other pulmonary disease before therapy and all remained asymptomatic during follow-up. New pulmonary interstitial FDG-uptake was detected on follow-up FDG-PET/CT between 1 and 3 months post-treatment, preceded computed tomography abnormalities in one case, and persisted for several months. FDG uptake was linear, subpleural with maximum Standardized uptake value (SUV) from 2.0 to 5.84. Rituximab-containing chemotherapy for NHL may be associated with asymptomatic late pulmonary toxicity characterised by a distinct FDG uptake pattern. Awareness of this finding is important and should not be confused with lymphoma.

A renal protocol for all ages and all indications: mercapto-acetyl-triglycine (MAG3) with simultaneous injection of furosemide (MAG3-F0): a 17-year experience.

Current clinical requirements mandate the existence of a renal diuretic protocol, which is fast and easy, applicable in all ages and for all indications, convenient for both the patient and the technologist, and provides diagnostic as well as prognostic information. Seventeen years ago a 25-minute protocol, after oral hydration, with no bladder catheterization, and simultaneous injection of mercapto-acetyl-triglycine (MAG(3)) and furosemide (MAG(3)-F(0)), was initiated. It initially was used for the evaluation of drainage and emerged as a protocol to also evaluate the renal parenchyma. Results of this protocol have been published individually, per clinical application. MAG(3)-F(0) was instrumental in the evaluation and prognosis of congenital disorders. For obstruction, in the newborn, an increasing renogram mandates intervention, whereas a downsloping one predicts spontaneous resolution. In children or adults, preoperatively or postoperatively, when the cortex was visualized and drained normally, there was no obstruction, even if urine was retained within a dilated collecting system or an extrarenal pelvis. For diseases of the renal parenchyma, the protocol enabled the diagnosis of acute pyelonephritis (APN) revealing the "regional parenchymal dysfunction," diagnostic of APN. Diffuse parenchymal diseases were characterized by increased residual cortical activity (RCA), and their progression was manifested as a deterioration of RCA. End-stage renal disease was characterized by lack of accumulation and retention. Trauma and leaks were identified with specific patterns. In renovascular hypertension (RVH), an increase in RCA after angiotension-converting enzyme inhibitors is diagnostic of RVH and prognostic of the beneficial effect of angioplasty on hypertension. In renal colic, stratification was possible into (1) complete or severe obstruction requiring immediate intervention, (2) mild obstruction allowing waiting, (3) spontaneous decompression (stunned kidney), and (4) no recent obstruction. In transplants, it enabled differentiation of acute tubular necrosis, acute or chronic rejection and nephrotoxicity, and identified infarcts, RVH, leaks and obstruction. Finally, this method allows for a quick semiquantification of renal function. The clinical usefulness of the MAG(3)-F(0) protocol in most congenital or acquired renal problems is proven through long-term clinical experience and has resulted in a substantial utilization of the test at our Center.

(123)I-mIBG scintigraphy in patients with known or suspected neuroblastoma: Results from a prospective multicenter trial.

BACKGROUND: A prospective trial was conducted to confirm the diagnostic performance of (123)I-mIBG scintigraphy in patients with known or suspected neuroblastoma. PROCEDURE: One hundred patients (mean age 4.7 years) were enrolled, 86 with a previous diagnosis of neuroblastoma, 13 with suspected disease based upon symptoms, imaging findings, and elevated catecholamines, and one adult with an abdominal tumor thought to be of neuroendocrine origin. All patients underwent whole-body planar imaging 24 hr following IV administration of 1-10 mCi (37-370 MBq) (123)I-mIBG. SPECT imaging of the thorax/abdomen/pelvis was performed in 51 patients. Images were interpreted by three blinded readers, with consensus requiring agreement of at least two readers. Disease status was confirmed by histopathology, imaging results, catecholamine measurements, and follow-up. RESULTS: Sixty-four patients had active disease, 30 were without disease, and 6 were judged indeterminate because of insufficient confirmatory data. (123)I-mIBG scintigraphy had a sensitivity of 88% (56/64) and specificity of 83% (25/30). Sensitivity was 91% (30/33) among the subset of subjects who had both planar and SPECT imaging. Among 53 patients with recent histopathology, sensitivity and specificity were 93% and 92%, respectively. Most false-negative interpretations were in patients with minimal residual disease (n = 4), while false-positive interpretations generally involved atypical adrenal or other physiological uptake (n = 4). CONCLUSIONS: This prospective multicenter trial of (123)I-mIBG scintigraphy documents high sensitivity and specificity of this imaging technique in patients with both newly diagnosed and previously treated neuroblastoma.

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.

Targeted bone marrow radioablation with 153Samarium-lexidronam promotes allogeneic hematopoietic chimerism and donor-specific immunologic hyporesponsiveness.

BACKGROUND: Transplantation tolerance, defined as acceptance of a graft by an otherwise fully immunocompetent host, has been an elusive goal. Although robust tolerance has been achieved by the induction of stable hematopoietic chimerism after bone marrow transplantation, lethal or sublethal radiation conditioning used to induce long-term chimerism precludes its clinical use. We studied whether targeted delivery of radiation to bone marrow could allow for bone marrow cell (BMC) engraftment, chimerism, and donor-specific tolerance in the absence of the side effects associated with external irradiation. METHODS: We administered a radioactive bone-seeking compound (Samarium-Lexidronam, Quadramet, Berlex Laboratories, Wayne, NJ) together with transient T-cell costimulatory blockade to recipient mice. Allogeneic BMCs were given 7 or 14 days after preconditioning. Costimulatory blockade was obtained by the use of an anti-CD154 antibody for 4 weeks. Chimerism was assessed by flow cytometry. Mice then received donor-specific and third-party skin grafts. Graft survival was analyzed with mechanisms of donor-specific hyporesponsiveness. RESULTS: High levels of stable chimerism across an allogeneic barrier were achieved in mice by a single administration of Samarium-Lexidronam, transient T-cell costimulatory blockade, and BMC transplantation. A large percentage of chimeric animals retained donor-derived skin grafts for more than 120 days without requiring additional immunosuppression, suggesting that harsh cytotoxic preconditioning is not necessary to achieve stable chimerism and donor specific hyporesponsiveness. Analysis of the T-cell repertoire in chimeras indicates T-cell deletional mechanisms. CONCLUSIONS: These data broaden the potential use of BMC transplantation for tolerance induction and argue for its potential in treating autoimmune diseases.

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.