Early evaluation of tumor response to 90Y-ibritumomab radioimmunotherapy in relapsed/refractory B cell non-Hodgkin lymphoma: what is the optimal timing for FDG-PET/CT?

PURPOSE: To determine the earliest optimal timing for assessment of early response following radioimmunotherapy in non-Hodgkin lymphoma patients using FDG-PET/CT. METHODS: FDG-PET/CT was performed prior to treatment (PET1), at 2 (PET2) weeks, and at 6 (PET3) weeks after 90Y-ibritumomab radioimmunotherapy in 55 patients. Response was evaluated based on the Deauville 5-point scale and Lugano criteria as well as semiquantitative analysis and compared with progression-free survival (PFS). RESULTS: PET 2 showed complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD) in 33, 13, 6, and 3 patients, respectively, while PET 3 in 41, 8, 3, and 3 patients, respectively. Mean SUVmax of 168 target lesions decreased over time (PET1, 2, 3; 5.58 ± 2.58, 1.87 ± 1.78, 1.75 ± 2.25, respectively). Progression or recurrence after a median of 12.6 months (range 2.6-72.0 months) was seen in 44 patients. Patients with CMR or metabolic response (CMR + PMR) on PET2 showed significantly longer PFS as compared to those who did not (p = 0.00028 and p = 0.029, respectively). A similar significant difference was observed based on PET3 (p = 0.00013 and p = 0.017, respectively). The same trend was observed when analyzing only the subgroup of patients with follicular lymphoma (N = 43/55) (p < 0.0001). CONCLUSION: Use of FDG-PET/CT findings with Lugano criteria for assessing early response to radioimmunotherapy after 6 weeks allowed for accurate evaluation and prognostic stratification, though scanning after 2 weeks was too soon to precisely evaluate response. KEY POINTS: • The optimal timing of FDG-PET/CT to obtain a suitable tool for assessment of response after 90 Y-ibritumomab radioimmunotherapy of lymphoma has not yet been defined. • Assessment after 6 weeks by FDG-PET/CT using the Lugano criteria accurately evaluates treatment response and prognosis. • FDG-PET/CT performed 2 weeks after radioimmunotherapy is too early as it significantly misses objective responses.

A Protease Inhibitor with Induction Therapy with Natural Interferon-ß in Patients with HCV Genotype 1b Infection.

The restoration of innate immune responses has potential as a novel therapeutic strategy for chronic hepatitis C (CHC). We compared the efficacy and safety of induction therapy (IT) with natural interferon-ß (n-IFN-ß) followed by pegylated-IFN-α/ribavirin (PR) alone (group A, n = 30) and IT with a protease inhibitor (PI) (simeprevir or vaniprevir)/PR (group B, n = 13) in CHC patients with genotype 1b and high viral loads. During IT with nIFN-ß, virologic response rates in group A and group B were 10% and 8% (p = 0.6792) at week 4, 30% and 16% (p = 0.6989) at week 12 and 47% and 20% (p = 0.0887) at week 24 respectively. During and after the treatment with PR alone or PI/PR, virologic response rates in groups A and B were 50% and 82% (p = 0.01535) at week 4, 53% and 91% (p = 0.006745) at week 8, 57% and 91% (p = 0.001126) at week 12, 57% and 100% (p < 0.001845) at the end of the treatment and 57% and 80% (p < 0.005166) after treatment cessation. IT with PI/PR linked to the restoration of innate immune response was tolerated well, overcame virological breakthrough, enhanced early virologic responses, and resulted in a sustained virologic response in difficult-to-treat CHC patients. IT with PI/PR is beneficial for treating difficult-to-treat CHC patients.

Use of scintigraphy to evaluate gastric accommodation and emptying: comparison with barostat.

BACKGROUND AND AIM: Scintigraphy is a useful noninvasive technique for assessment of gastric motility, especially emptying, but there is little knowledge of use of the technique to assess gastric accommodation. Therefore, to clarify the usefulness of scintigraphy as a technique for assessing gastric accommodation, we compared scintigraphy with barostat, the gold standard modality. METHODS: Twenty healthy volunteers (14 men, six women; mean age, 28.5 ± 5.4 years) were enrolled in the study. The volunteers ingested a radiolabeled ((99m) Tc) test meal and scintigraphic images were recorded. Radioactivity in the upper third and whole stomach was calculated to evaluate accommodation. In the barostat procedure, gastric accommodation was evaluated by measuring the maximum volume of the distended balloon. Thereafter, correlation between scintigraphic and barostat accommodation was investigated. Intra-and inter-observer variation of the scintigraphic test results were also assessed. Finally, the diagnostic performance of scintigraphy was evaluated by using sumatriptan as a positive control. RESULTS: Measurements of accommodation by scintigraphy and barostat correlated (r = 0.524, P < 0.05). Sumatriptan significantly increased scintigraphically measured gastric accommodation (with sumatriptan, 51.5 ± 16.4%; without sumatriptan, 38.4 ± 13.8%) (P < 0.01), and had significantly (P < 0.05) delayed 50% half emptying time at 60, 90, 120, and 150 min after the start of the experiment. The data from repeated scintigraphic tests were highly reproducible (r = 0.804) with significant differences not observed among the investigators (inter-observer variation = 0.932, intra-observer variation = 0.898). CONCLUSION: Gastric scintigraphy is a useful technique for assessing gastric accommodation and emptying.

Primary epithelioid hemangioendothelioma of the retroperitoneum: report of a case.

We herein report the case of a 48-year-old Japanese female with retroperitoneal epithelioid hemangioendothelioma (EHE), a rare malignant vascular tumor of intermediate grade. She was referred to our hospital because a retroperitoneal tumor was found during a medical checkup, in which strong accumulation of (18)F-fluorodeoxyglucose (FDG) was observed by (18)F-FDG-positron emission tomography (PET). A histological examination of the resected tumor revealed that it consisted of large epithelioid cells with vesicular nuclei, and clear cells with vacuolated cytoplasm and intracytoplasmic lumina. These cells expressed CD31 and vimentin, and the final pathological diagnosis was EHE. Postoperative surveillance with FDG-PET revealed distant metastasis in Virchow's lymph node 7 months after the operation. After dissection of the metastatic lymph node, the patient has been free from recurrence for 13 months. Close follow-up with FDG-PET seemed to be useful for surveillance of the recurrence of this tumor with unpredictable behavior, making an early treatment for the recurrent lesions possible.

Correction of nonuniform attenuation and image fusion in SPECT imaging by means of separate X-ray CT.

Improvements in image quality and quantitation measurement, and the addition of detailed anatomical structures are important topics for single-photon emission tomography (SPECT). The goal of this study was to develop a practical system enabling both nonuniform attenuation correction and image fusion of SPECT images by means of high-performance X-ray computed tomography (CT). A SPECT system and a helical X-ray CT system were placed next to each other and linked with Ethernet. To avoid positional differences between the SPECT and X-ray CT studies, identical flat patient tables were used for both scans; body distortion was minimized with laser beams from the upper and lateral directions to detect the position of the skin surface. For the raw projection data of SPECT, a scatter correction was performed with the triple energy window method. Image fusion of the X-ray CT and SPECT images was performed automatically by auto-registration of fiducial markers attached to the skin surface. After registration of the X-ray CT and SPECT images, an X-ray CT-derived attenuation map was created with the calibration curve for 99mTc. The SPECT images were then reconstructed with scatter and attenuation correction by means of a maximum likelihood expectation maximization algorithm. This system was evaluated in torso and cylindlical phantoms and in 4 patients referred for myocardial SPECT imaging with Tc-99m tetrofosmin. In the torso phantom study, the SPECT and X-ray CT images overlapped exactly on the computer display. After scatter and attenuation correction, the artifactual activity reduction in the inferior wall of the myocardium improved. Conversely, the incresed activity around the torso surface and the lungs was reduced. In the abdomen, the liver activity, which was originally uniform, had recovered after scatter and attenuation correction processing. The clinical study also showed good overlapping of cardiac and skin surface outlines on the fused SPECT and X-ray CT images. The effectiveness of the scatter and attenuation correction process was similar to that observed in the phantom study. Because the total time required for computer processing was less than 10 minutes, this method of attenuation correction and image fusion for SPECT images is expected to become popular in clinical practice.

[Nuclear gastroenterology].

Application of nuclear medicine for gastroenterology, especially the liver, portal circulation and alimentary tract was described. In the liver, radiocolloid scintigraphy is useful for the diagnosis and follow-up study of chronic liver diseases. 99mTc-GSA scintigraphy plays a role for the evaluation of hepatic functional reserve. 99mTc-PMT used for hepatobiliary imaging, is also useful for the diagnosis of hepatic tumor and extra-hepatic metastasis of hepatocellular carcinoma. In the study of portal circulation, various administration sites such as intrasplenic, rectal, oral, and intravenous have been reported. In the evaluation of motility function of alimentary tract, estimation of gastric emptying time is well known. Condensed image created from serial esophageal scintigrams using computer processing is also useful for the quantitative and qualitative evaluation of esophageal motility function and gastro-esophageal reflux. Abdominal scintigraphy with 99mTc-human serum albumin enables imaging diagnosis of protein-loosing gastroenteropathy.

Nuclear neuroimaging in acute and subacute ischemic stroke.

Neuroimaging in ischemic stroke continues to be one of the most developing fields in nuclear medicine. Many studies have established the efficacy of blood flow and metabolism measurements in acute ischemic stroke. Although the release of recombinant tissue plasminogen activator in clinical practice has minimized the use of SPECT or PET in the first few hours of ischemic stroke onset, implementing these techniques into a set of initial examinations is still beneficial to exclude risky patients for reperfusion therapy beyond several hours after onset. Rescuing of viable tissue suffering ischemic penumbra is an important target of early therapeutic strategy. Ischemic penumbra can be visualized by means of perfusion imaging, central type benzodiazepine receptor imaging, and hypoxy imaging. In the later phase of subacute ischemic stroke, inflammation and apoptosis can be visualized by means of peripheral-type benzodiazepine receptor imaging and annexin V imaging, respectively. Imaging of the penumbra and cellular responses will help evaluate the effects of drugs and interventions for ischemic stroke, suggesting its potential as a marker of the efficacy of future therapeutic regimens.

Preoperative estimation of asialoglycoprotein receptor expression in the remnant liver from CT/99mTc-GSA SPECT fusion images correlates well with postoperative liver function parameters.

BACKGROUND: Accurate preoperative estimation of remnant liver function is critically important for hepatic surgery, and the expression of asialoglycoprotein receptors (ASGPR) is associated with hepatic function. METHODS: Thirty-two patients with hepatocellular carcinoma who underwent surgical resection were studied. To estimate the expression of ASGPR in the remnant liver, simulated surgery was performed on fusion images that combined data from (99m)technetium-galactosyl human serum albumin ((99m)Tc-GSA)/single photon emission computed tomography (SPECT) and computed tomography (CT) scanning. The liver uptake ratio (LUR) of (99m)Tc-GSA and the functional liver volume (FLV) in the remnant liver were predicted and were compared with postoperative liver function parameters. RESULTS: The LUR of (99m)Tc-GSA was strongly correlated with the extent of hepatic ASGPR expression (r = 0.944, p = 5.01 x 10(-16)), being confirmed to be a reliable parameter for the evaluation of liver function. The estimated remnant LUR, but not the estimated remnant FLV, was significantly correlated with postoperative liver function parameters, such as serum total bilirubin (r = -0.430, p < 0.05), prothrombin activity (r = 0.515, p < 0.01), and serum cholinesterase activity (r = 0.546, p < 0.01) at 1 week. CONCLUSION: Preoperative estimation of the extent of ASGPR expression in the remnant liver on CT/GSA-SPECT fusion images correlated well with postoperative liver function parameters, suggesting its usefulness for surgical decisions.

Multiple cytokine profiling of the therapeutic responses to ribavirin and pegylated interferon-alpha2b using an "induction" approach with natural interferon-beta in difficult-to-treat chronic hepatitis C.

Cyclic and periodic IFN treatment (CPIT) consisting of induction treatment with nIFN-beta followed by maintenance treatment with IFN-alpha could prevent viral breakthrough and achieve rapid virological response (RVR) and early virological response (EVR) in chronic hepatitis C (CHC). The efficacy and immune response of RBV+PEG-IFN-alpha2b using induction approach with CPIT (novel combination treatment: NCT) in 7 CHC patients with genotype 1b and high viral load were evaluated. A biometric multiplex serum cytokine assay was utilized to characterize the immunomodulatory effect. RVR and EVR were 7/7 and 7/7, respectively. Viral titers dropped below detectable levels in five patients with sustained virological response (SVR) before the end of CPIT (early virological responder: EAVR), and two patients without SVR after the end of CPIT (late virological responder: LAVR). At baseline, in EAVR compared with the controls, IL-6 and IL-15, CXCL-8 and CXCL-10 levels were significantly higher (P < 0.05); IL-10 and IL-13 levels were significantly lower (P < 0.05); and the IL-12 level was lower. In LAVR, GM-CSF, CXCL-8 and CXCL-10, and CCL-4 levels were significantly higher (P < 0.05); and IL-10 and IL-12 were lower than the controls. In EAVR but not LAVR, the IL-12 increased and the CCXL-8 decreased significantly (P < 0.05). In conclusion, NCT-induced viral clearance leading to improvement in the innate immune response resulting in SVR in CHC with genotype 1b and high viral load.