Targeted Radiation Delivery before Haploidentical HCT for High-risk Leukemia or MDS Patients Yields Long-term Survivors.

PURPOSE: Hematopoietic cell transplantation (HCT) has curative potential for myeloid malignancies, though many patients cannot tolerate myeloablative conditioning with high-dose chemotherapy alone or with total-body irradiation (TBI). Here we report long-term outcomes from a phase I/II study using iodine-131 (131I)-anti-CD45 antibody BC8 combined with nonmyeloablative conditioning prior to HLA-haploidentical HCT in adults with high-risk relapsed/ refractory acute myeloid or lymphoid leukemia (AML or ALL), or myelodysplastic syndrome (MDS; ClinicalTrials.gov, NCT00589316). PATIENTS AND METHODS: Patients received a tracer diagnostic dose before a therapeutic infusion of 131I-anti-CD45 to deliver escalating doses (12-26 Gy) to the dose-limiting organ. Patients subsequently received fludarabine, cyclophosphamide (CY), and 2 Gy TBI conditioning before haploidentical marrow HCT. GVHD prophylaxis was posttransplant CY plus tacrolimus and mycophenolate mofetil. RESULTS: Twenty-five patients (20 with AML, 4 ALL and 1 high-risk MDS) were treated; 8 had ≥ 5% blasts by morphology (range 9%-20%), and 7 had previously failed HCT. All 25 patients achieved a morphologic remission 28 days after HCT, with only 2 patients showing minimal residual disease (0.002-1.8%) by flow cytometry. Median time to engraftment was 15 days for neutrophils and 23 days for platelets. Point estimates for overall survival and progression-free survival were 40% and 32% at 1 year, and 24% at 2 years, respectively. Point estimates of relapse and nonrelapse mortality at 1 year were 56% and 12%, respectively. CONCLUSIONS: 131I-anti-CD45 radioimmunotherapy prior to haploidentical HCT is feasible and can be curative in some patients, including those with disease, without additional toxicity.

Skin Malignancies: Imaging Review with Radiologic-Histopathologic Correlation.

Skin malignancies are commonly encountered as primary or incidental findings. Neoplasms that affect the skin include primary (basal cell carcinoma, squamous cell carcinoma, melanoma, and Merkel cell carcinoma) and secondary (mesenchymal neoplasms, lymphoma, and metastases) tumors. Imaging provides valuable anatomic information (tumor size, depth of involvement, presence of distant metastasis, and data for guiding biopsy) and functional information (metabolic activity and sentinel node mapping data). This information, in addition to biopsy results, improves the histopathologic characterization of tumors and treatment planning. Various histopathologic types of the same entity exhibit different biologic behavior and have different imaging features. Familiarity with the multimodality imaging features, histopathologic characteristics, and various modes of dissemination (direct invasion; perineural, lymphatic, and hematogenous spread) of the most common skin malignancies helps radiologists narrow the differential diagnosis in clinical practice. ©RSNA, 2023 Supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Ventilation-Perfusion Scan: A Primer for Practicing Radiologists.

Lung scintigraphy, or ventilation-perfusion (V/Q) scan, is one of the commonly performed studies in nuclear medicine. Owing to variability in clinical applications and different departmental workflows, many trainees are not comfortable interpreting the results of this study. This article provides a simplified overview of V/Q imaging, including a review of its technique, interpretation methods, and established and emerging clinical applications. The authors review the role of V/Q imaging in evaluation of acute and chronic pulmonary embolism, including the role of SPECT/CT and comparing V/Q scan with CT angiography. In addition, a variety of other applications of pulmonary scintigraphy are discussed, including congenital heart disease, pretreatment planning for lung cancer and emphysema, posttransplant imaging for bronchiolitis obliterans, and less common vascular and nonvascular pathologic conditions that may be detected with V/Q scan. This article will help radiologists and residents interpret the results of V/Q scans and understand the various potential clinical applications of this study. Online supplemental material is available for this article. ©RSNA, 2021.

Yttrium-90 Anti-CD45 Immunotherapy Followed by Autologous Hematopoietic Cell Transplantation for Relapsed or Refractory Lymphoma.

Autologous hematopoietic cell transplantation (AHCT) is a standard of care for several subtypes of high-risk lymphoma, but durable remissions are not achieved in the majority of patients. Intensified conditioning using CD45-targeted antibody-radionuclide conjugate (ARC) preceding AHCT may improve outcomes in lymphoma by permitting the delivery of curative doses of radiation to disease sites while minimizing toxicity. We performed sequential phase I trials of escalating doses of yttrium-90 (90Y)-labeled anti-CD45 antibody with or without BEAM (carmustine, etoposide, cytarabine, melphalan) chemotherapy followed by AHCT in adults with relapsed/refractory or high-risk B cell non-Hodgkin lymphoma (NHL), T cell NHL (T-NHL), or Hodgkin lymphoma (HL). Twenty-one patients were enrolled (16 NHL, 4 HL, 1 T-NHL). Nineteen patients received BEAM concurrently. No dose-limiting toxicities were observed; therefore, the maximum tolerated dose is estimated to be ≥34 Gy to the liver. Nonhematologic toxicities and engraftment kinetics were similar to standard myeloablative AHCT. Late myeloid malignancies and 100-day nonrelapse deaths were not observed. At a median follow-up of 5 years, the estimates of progression-free and overall survival of 19 patients were 37% and 68%, respectively. Two patients did not receive BEAM; one had stable disease and the other progressive disease post-transplant. The combination of 90Y-anti-CD45 with BEAM and AHCT was feasible and tolerable in patients with relapsed and refractory lymphoma. The use of anti-CD45 ARC as an adjunct to hematopoietic cell transplantation regimens or in combination with novel therapies/immunotherapies should be further explored based on these and other data.

90Y-labeled anti-CD45 antibody allogeneic hematopoietic cell transplantation for high-risk multiple myeloma.

To improve disease control without increasing the toxicity of a reduced-intensity allogeneic hematopoietic cell transplantation (HCT) in multiple myeloma (MM), a phase I trial was performed using an antibody-radionuclide conjugate targeting CD45 (90Y-DOTA-BC8) as conditioning. 90Y-DOTA-BC8 was combined with fludarabine and low-dose TBI followed by allogeneic HCT in patients with MM and ≥1 adverse risk characteristic at diagnosis, relapse after autologous transplant, or plasma cell leukemia (PCL). The primary objective was to estimate the maximum tolerated radiation absorbed dose. Fourteen patients were treated (one with PCL, nine failed prior autologous HCT, and nine with ≥1 adverse cytogenetics). Absorbed doses up to 32 Gy to liver were delivered. No dose-limiting toxicities occurred. Non-hematologic toxicities were manageable and included primarily gastrointestinal (43%) and metabolic/electrolyte disturbances (36%). Treatment-related mortality at 100 days was 0%. At a median follow-up of 5 years, the overall survival was 71% (median not reached) and the progression-free survival was 41% (median 40.9 months). The incorporation of CD45-targeted radioimmunotherapy (RIT) into a reduced-intensity allogeneic HCT is well-tolerated and may induce long-term remissions among patients with poor-risk MM, supporting further development of RIT-augmented conditioning regimens for HCT.

The Peritoneum: What Nuclear Radiologists Need to Know.

The peritoneum is the largest and most complex serous membrane in the human body. The peritoneal membrane is composed of a layer of mesothelium supported by a thin layer of connective tissue. The peritoneum is one continuous sheet, forming two layers and a potential space between them - the peritoneal cavity- which is subdivided into multiple communicating spaces containing small amount of serous fluid that facilitates frictionless movement of mobile intraabdominal viscera. Peritoneum also contributes to fluid exchange mechanism and plays a role in immune response. The peritoneum is subject to many neoplastic and non-neoplastic processes including infections, trauma, developmental and inflammatory processes. Different Nuclear Medicine imaging techniques can be used to diagnose peritoneal diseases, most of these techniques can be customized depending on the clinical scenario and expected findings. Peritoneal scintigraphy can detect abnormal peritoneal communication or compartmentalization. Several nuclear medicine techniques can help characterize intraperitoneal fluid collections and differentiate sterile from infected fluid. PET imaging plays an important role in imaging of different neoplastic and non-neoplastic peritoneal pathologies. Nuclear radiologists need to be familiar with peritoneal anatomy and pathology to interpret peritoneal findings in dedicated peritoneal nuclear medicine imaging studies, as part of more general nuclear medicine scans, or on CT or MRI component of hybrid imaging studies. The purpose of this article is to review the normal peritoneal anatomy, various pathologic processes involving the peritoneum, and different nuclear medicine and hybrid imaging techniques that can help detect, characterize, and follow up peritoneal pathology.

Hepatopulmonary shunting on Tc99m-MAA liver mapping: correlation with dynamic cross-sectional imaging and description of different shunting patterns.

PURPOSE: The purpose of the study was to correlate lung shunt fraction (LSF) calculated by intra-arterial injection of Technetium-99m (Tc-99m)-labeled macroaggregated albumin (MAA) in a hepatic artery branch with the presence of certain patterns of vascular shunts on dynamic CT or MRI of the liver. METHODS: This retrospective study was approved by the institutional review board and informed consent was waived. We reviewed 523 MAA scans in 453 patients (301 men, 152 women) performed from July 2007 to June 2015 and their correlative cross-sectional imaging. Patterns of vascular shunts on dynamic CT or MRI performed within 3 months of the MAA study and that potentially divert hepatic arterial inflow to the systemic venous return were defined as "target shunts." Dynamic CT or MRI was classified into three groups with target shunt present, absent, or indeterminate. The mean LSF was compared across the first and second groups using paired t test. RESULTS: 342 CT and MRI studies met inclusion criteria: target shunts were present in 63 studies, absent in 271 studies, and 8 studies were indeterminate. When target shunts were visualized, the mean LSF on corresponding MAA scans was 12.9 ± 10.36% (95% CI 10.29-15.15%) compared to 4.3 ± 3.17% (95% CI 3.93-4.68%) when no target shunt was visualized. The difference was statistically significant (p value < 0.001). Identified target shunts were either direct (arteriohepatic venous shunt) or indirect (arterioportal shunt combined with a portosystemic shunt). CONCLUSIONS: Visualizing certain patterns of vascular shunting on a dynamic CT or MRI scan is associated with high LSF.

Spontaneous Intracranial Hypotension With Site of Leak Detected Only After 111In-DTPA Cisternogram.

A 54-year-old man with a 3-week history of orthostatic headache and acute on chronic subdural hematoma presented with imaging findings suggestive of spontaneous intracranial hypotension. Three myelograms were negative for leak, and nontargeted epidural blood patches did not result in symptom relief. A cerebrospinal fluid leak study using In-DTPA with SPECT/CT demonstrated a focal area of asymmetric activity at the left C2 nerve root. A left C2 root tie-off, targeted epidural blood patch, and Dura seal glue resulted in resolution of patient symptomatology highlighting the importance of fused SPECT/CT images in detection of an occult cerebral spinal fluid leak.

Advances in PET Imaging of Degenerative, Cerebrovascular, and Traumatic Causes of Dementia.

In this review we present the most recent advances in nuclear medicine imaging as a diagnostic and management tool for dementia. The clinical diagnosis of dementia syndromes can be challenging for physicians, particularly in the early stages of disease. Given the growing number of individuals affected by dementia, early and accurate diagnosis can lead to improved clinical management of patients. Although tests are available for exclusion of certain causes of cognitive impairment, the results rarely allow the clinician to make a definitive diagnosis. For this reason, information obtained from imaging ("imaging biomarkers") is playing an increasingly important role in the workup of patients with suspected dementia. Imaging biomarkers also provide indispensable tools for clinical and preclinical studies of dementing illnesses to elucidate their pathophysiology and to develop better therapies. A wide range of imaging has been used to diagnose and investigate neurodegenerative disorders including structural, cerebral perfusion, glucose metabolism, neurochemical, and molecular imaging. In the first section, we discuss the imaging methods used in clinical practice to diagnose dementia as well as explore additional experimental modalities that are currently used as research tools. In the second section, a comprehensive review covering the myriad aspects of vascular disease as a cause of dementia is presented and illustrated with MRI- and PET-focused case examples. In the third section, advances in imaging Alzheimer disease pathology are emphasized by reviewing current approaches for PET imaging with ß-amyloid imaging agents. We provide an outline for the appropriate use criteria for ß-amyloid imaging agents in dementia. In addition, the recognition of the importance of neocortical neurofibrillary tangles as related to Alzheimer disease progression has led to the development of promising tau imaging agents such as [(18)F]T807. The last section provides a history brain trauma as a cause of chronic traumatic encephalopathy. Although the recognition of cognitive deficits from brain trauma dates back to the early part of last century, recent advances in our understanding of the neurobiology has led to the hope of developing molecular imaging methods for earlier diagnoses and treatment. This has become increasingly important given the raised public and physician awareness of the high incidence of this pathology in military conflicts and sports-related injuries. Overall advancements in nuclear medicine imaging have led to an improvement in the detection and accurate identification of dementia and its underlying causes. With both primary and secondary causes of dementia demonstrating often overlapping presentations, nuclear medicine imaging can play a key role not only in the diagnosis but the understanding of dementia. With earlier diagnosis and better understanding comes the hope of improved treatments or possibly someday a cure.

Differential alterations of dopamine transporter in the striatum and midbrain in patients with parkinsonian syndrome.

OBJECTIVES: Differential vulnerabilities of subregional dopamine neurons have been suggested in movement disorders such as idiopathic Parkinson disease. In this study, we examined dopamine transporter (DaT) density in the striatum versus midbrain (MB) in patients with nigrostriatal denervation. METHODS: Brain SPECT was performed in 39 patients with parkinsonian syndrome (age 61 ± 15 years, 18 male patients) 4 hours after IV injection of 3 to 5 mCi 123I ioflupane using SPECT-CT acquisition. Images were reconstructed using OSEM with resolution recovery and correction for scatter and attenuation based on a low-dose CT. Peak pixel counts within the caudate head (CA), mid putamen (PT), and MB localized by sagittal CT, as well as averaged counts around the calcarine fissure as reference, were determined by region-of-interest analysis. Semiquantitative DaT values were expressed as CA, PT, or MB uptake relative to the reference. We then assessed the relationship between the MB measurements and independent clinical evaluation of motor symptoms in these patients. RESULTS: Averaged striatal DaT values for both hemispheres ranged from 1.67 to 6.59 for CA, 1.50 to 5.33 for PT, and 1.08 to 2.24 for MB. Within the high striatal DaT group (mean, 4.76 [SD, 0.55]) and low DaT group (mean, 2.71 [SD, 0.58]; dichotomy defined as a threshold of 4), mean DaT values in MB were 1.68 (SD, 0.32) and 1.53 (SD, 0.29), respectively, indicating nonsignificant 9% decrease (P > 0.15) in comparison to 43% decrease in the averaged striatal uptake. Within the high striatal DaT group, Pearson correlations between DaT values of CA and PT versus MB were highly significant at 0.81 and 0.82 (P ≤ 0.001), respectively, but those correlations were not significant, 0.35 (P > 0.05) and 0.06 (P > 0.75), in the low striatal DaT group. Midbrain uptake measurements did not correlate with motor symptoms (bradykinesia, tremor, rigidity, and postural instability). CONCLUSIONS: These findings indicate that reductions in DaT values in the striatum and MB are not necessarily simultaneous with the process of nigrostriatal denervation, and correlation of DaT values among CA/PT and MB becomes weaker as the denervation becomes more severe. Differential regional DaT loss may indicate differential vulnerability of DaT-containing neurons in these structures or could be in part related to tracer binding to non-DaT targets.

9°Y-Ibritumomab tiuxetan, fludarabine, and TBI-based nonmyeloablative allogeneic transplantation conditioning for patients with persistent high-risk B-cell lymphoma.

Nonmyeloablative allogeneic transplantation (NMAT) infrequently cures active chemoresistant, bulky, or aggressive B-cell lymphoma (B-cell non-Hodgkin lymphoma [B-NHL]). We hypothesized that 9°Y-ibritumomab tiuxetan-based NMAT would facilitate early cytoreduction in such patients promoting improved long-term disease control by the allogeneic graft. Forty high-risk B-NHL patients with persistent disease received 0.4 mCi/kg (maximum, 32 mCi/kg) 9°Y-ibritumomab tiuxetan, fludarabine, and 2 Gy total body irradiation and matched-related (15) or unrelated (25) transplantation. Baseline features included: median age, 58 years (range, 29-69 years); median prior regimens, 6 (range, 3-12); chemosensitive disease, 6 (15%); bulk > 5 cm, 17 (range, 5.2-18.6 cm, 43%); diffuse large B-cell lymphoma, 14 (35%); and comorbidity score > zero, 34 (85%). Early responses were observed in 24 (60%, 14 complete remission/complete remission unconfirmed, 10 partial response) patients, including 17 of 29 (59%) with chemotherapy-resistant disease and 10 (59%) with bulk > 5 cm. The estimated 30-month survival, progression-free survival, and nonrelapse mortality were 54.1%, 31.1%, and 15.9%, respectively. Early response, baseline platelet counts over 25 000/µL, indolent histology, and related donors were associated with improved survival. The addition of 9°Y-ibritumomab tiuxetan to NMAT is safe and yields early responses and prolonged disease control in some of the highest-risk B-NHL patients. This trial was registered at www.clinicaltrials.gov as #NCT00119392.