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Summary: To assess efficacy of radioimmunotherapy (RIT) in follicular lymphoma, data from 281 patients collected in the RIT Network, with a median follow‐up of 8·2 years after RIT were analysed. RIT was given at first line in 18·5% and at relapse in 81·5%. Following first line therapy, 76·9% achieved complete remission (CR), 9·6% partial remission (PR), 1·9% stable disease (SD) and 1·9% had progressive disease (PD); response was not documented in 9·7%. At relapse, the rate of CR was 48·5% and that of PR was 16·6%, SD 2·6% and PD 10·5%; response was not documented in 21·8%. After median follow‐up of 8·2 years, median progression‐free survival (PFS) for all was 2·54 years, median overall survival (OS) was not reached. Median PFS and OS (both not reached) were significantly better in first line, compared to RIT at relapse (PFS, 2·11 years; OS, 10·8 years; P = 0·0037 and P = 0·0021, respectively). Overall 8‐year PFS was 33·9%, 53·6% for first line and 29·6% for relapsed individuals. Overall 8‐year OS was 58·8%, 78·1% for first line and 54·5% for relapsed patients. Thirty‐five patients (12·5%) developed secondary malignancy and 16 patients (5·7%) experienced transformation into aggressive lymphoma. RIT is a safe and effective treatment option for follicular lymphoma, both at front line and relapse with an 8‐year PFS of 53·6% and 29·6%, respectively. [ABSTRACT FROM AUTHOR]

Standard conditioning regimens for autologous stem cell transplantation (ASCT) are often not tolerated by elderly patients, on one hand. Single high-dose melphalan, on the other hand, has been shown to be safe and active as a pretransplant preparative regimen in elderly patients. Y90 -Ibritumomab tiuxetan (Y90 -IT) is well tolerated and feasible in the transplantation setting. We therefore investigated the combination of high-dose melphalan and Y90 -IT as a conditioning regimen for patients ≥65 years of age. Patients with relapsed or resistant CD20-positive lymphoma in remission after salvage chemotherapy could be enrolled. High-dose therapy consisted of standard dose Y90 -IT (0.4-mCi/kg body weight) followed by melphalan at escalating doses (100, 140, 170 and 200 mg/m2 ) and ASCT. The primary objective was to identify the maximum tolerated dose; secondary end points were complete response (CR) rate 100 days after transplantation and toxicity. Twenty patients (median age 72 years) were included. No DLT occurred at any dose level. Thirteen patients completed the treatment, 11 were evaluable for response. Seven patients did not complete treatment because of mobilization failure (n = 3), progressive disease (n = 2), worsening of cardiac function (n = 1), and grade 3 dyspnea (n = 1). Seven patients achieved a CR/complete remission/unconfirmed (CRu) and 2 had stable disease. Five out of 7 responding patients were still alive more than 3 years after transplantation. The 2 patients with SD had a long-term survival of 3 and 5 years, respectively. Nonhematological grade 3 or higher treatment related adverse events (AEs) were infection (n = 6), including 2 cases of febrile neutropenia, diarrhea (n = 3), mucositis, anorexia, viral hepatitis, hypokalemia, dehydration, and multiorgan failure (n = 1 for each). The combination of Y90 -IT and high-dose melphalan is feasible before ASCT for elderly patients, with promising activity and manageable toxicity. [ABSTRACT FROM AUTHOR]

Purpose: The biokinetics and dosimetry of In-DOTA-NOC-ATE (NOCATE), a high-affinity ligand of SSTR-2 and SSTR-5, and In-DTPA-octreotide (Octreoscan™, OCTREO) were compared in the same patients. Methods: Seventeen patients (10 men, 7 women; mean age 60 years), referred for an OCTREO scan for imaging of a neuroendocrine tumour (15), thymoma (1) or medullary thyroid carcinoma (1), agreed to undergo a second study with NOCATE. Whole-body anterior-posterior scans were recorded 0.5 (100 % reference scan), 4, 24 and 48 h (17 patients) and 120 h (5 patients) after injection. In 16 patients the OCTREO scan (178 ± 15 MBq) was performed 16 ± 5 days before the NOCATE scan (108 ± 14 MBq) with identical timing; 1 patient had the NOCATE scan before the OCTREO scan. Blood samples were obtained from 14 patients 5 min to 48 h after injection. Activities expressed as percent of the initial (reference) activity in the whole body, lung, kidney, liver, spleen and blood were fitted to biexponential or single exponential functions. Dosimetry was performed using OLINDA/EXM. Results: Initial whole-body, lung and kidney activities were similar, but retention of NOCATE was higher than that of OCTREO. Liver and spleen uptakes of NOCATE were higher from the start ( p < 0.001) and remained so over time. Whole-body activity showed similar α and β half-lives, but the β fraction of NOCATE was double that of OCTREO. Blood Tβ for NOCATE was longer (19 vs. 6 h). As a result, the effective dose of NOCATE (105 μSv/MBq) exceeded that of OCTREO (52 μSv/MBq), and the latter result was similar to the ICRP 106 value of 54 μSv/MBq. Differential activity measurement in blood cells and plasma showed an average of <5 % of NOCATE and OCTREO attached to globular blood components. Conclusion: NOCATE showed a slower clearance from normal tissues and its effective dose was roughly double that of OCTREO. [ABSTRACT FROM AUTHOR]

Purpose: Quantification of myocardial blood flow (MBF) with generator-produced Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate Rb-measured MBF in relation to that measured using O-water, as a tracer 100% of which can be extracted from the circulation even at high flow rates, in healthy control subject and patients with mild coronary artery disease (CAD). Methods: MBF was measured at rest and during adenosine-induced hyperaemia with Rb and O-water PET in 33 participants (22 control subjects, aged 30 ± 13 years; 11 CAD patients without transmural infarction, aged 60 ± 13 years). A one-tissue compartment Rb model with ventricular spillover correction was used. The Rb flow-dependent extraction rate was derived from O-water measurements in a subset of 11 control subjects. Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson's correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin's concordance correlation ρ (measuring both precision and accuracy) were used. Results: Over the entire MBF range (0.66-4.7 ml/min/g), concordance was excellent for MBF ( r = 0.90, [Rb-O-water] mean difference ± SD = 0.04 ± 0.66 ml/min/g, LoA = −1.26 to 1.33 ml/min/g, ρ = 0.88) and MFR (range 1.79-5.81, r = 0.83, mean difference = 0.14 ± 0.58, LoA = −0.99 to 1.28, ρ = 0.82). Hyperaemic MBF was reduced in CAD patients compared with the subset of 11 control subjects (2.53 ± 0.74 vs. 3.62 ± 0.68 ml/min/g, p = 0.002, for O-water; 2.53 ± 1.01 vs. 3.82 ± 1.21 ml/min/g, p = 0.013, for Rb) and this was paralleled by a lower MFR (2.65 ± 0.62 vs. 3.79 ± 0.98, p = 0.004, for O-water; 2.85 ± 0.91 vs. 3.88 ± 0.91, p = 0.012, for Rb). Myocardial perfusion was homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in MBF among the coronary artery territories ( p > 0.31). Conclusion: Quantification of MBF with Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routine. [ABSTRACT FROM AUTHOR]

The aim of this document is to provide general information about mIBG scintigraphy in cancer patients. The guidelines describe the mIBG scintigraphy protocol currently used in clinical routine, but do not include all existing procedures for neuroendocrine tumours. The guidelines should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary from one country to another and from one medical institution to another. The present guidelines have been prepared for nuclear medicine physicians and intend to offer assistance in optimizing the diagnostic information that can currently be obtained from mIBG scintigraphy. The corresponding guidelines of the Society of Nuclear Medicine (SNM) and the Dosimetry, Therapy and Paediatric Committee of the EANM have been taken into consideration, and partially integrated into this text. The same has been done with the most relevant literature on this topic, and the final result has been discussed within a group of distinguished experts. [ABSTRACT FROM AUTHOR]

Non-Hodgkin's lymphoma (NHL) comprises both indolent forms, including follicular lymphoma (FL) and marginal zone lymphoma (MZL), and aggressive forms, including diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). FL and DLBCL are the most common subtypes of indolent and aggressive NHL, respectively. Although these lymphomas exhibit different clinical behaviors and outcomes, the prognosis is negatively affected in both DLBCL and FL by the lack of a complete response (CR) with standard treatment options. The aim of therapy should therefore be achievement of a CR, which is not only associated with longer progression-free survival (PFS) and overall survival times, but is also a prerequisite for a cure, particularly in DLBCL. Consolidation treatment with radioimmunotherapy (RIT) is an innovative treatment approach to increase CR rates. Phase II studies have indicated promising results with yttrium-90 (90Y)-ibritumomab tiuxetan and iodine-131 (131I)-tositumomab as consolidation following induction therapy for previously untreated patients with advanced FL. More recently, investigators reported a marked increase in CR rates and significant improvements in PFS using standard chemotherapy regimens followed by 90Y-ibritumomab tiuxetan in a phase III randomized trial in patients with previously untreated FL. Data also suggest that RIT may play a role in the treatment of high-risk DLBCL, with encouraging PFS results from a phase II trial of 90Y-ibritumomab tiuxetan consolidation following induction with rituximab plus chemotherapy in elderly patients with previously untreated DLBCL. With the higher CR rates and longer PFS times observed in patients with FL and DLBCL, as well as encouraging early data from MZL and MCL consolidation trials, RIT appears to have an important role in the treatment of patients with NHL. [ABSTRACT FROM AUTHOR]

Combined positron emission tomography and computed tomography (PET/CT) scanners play a major role in medicine for in vivo imaging in an increasing number of diseases in oncology, cardiology, neurology, and psychiatry. With the advent of short-lived radioisotopes other than 18F and newer scanners, there is a need to optimize radioisotope activity and acquisition protocols, as well as to compare scanner performances on an objective basis. The Discovery-LS (D-LS) was among the first clinical PET/CT scanners to be developed and has been extensively characterized with older National Electrical Manufacturer Association (NEMA) NU 2-1994 standards. At the time of publication of the latest version of the standards (NU 2-2001) that have been adapted for whole-body imaging under clinical conditions, more recent models from the same manufacturer, i.e., Discovery-ST (D-ST) and Discovery-STE (D-STE), were commercially available. We report on the full characterization both in the two- and three-dimensional acquisition mode of the D-LS according to latest NEMA NU 2-2001 standards (spatial resolution, sensitivity, count rate performance, accuracy of count losses, and random coincidence correction and image quality), as well as a detailed comparison with the newer D-ST widely used and whose characteristics are already published. [ABSTRACT FROM AUTHOR]

The first aim of the study was to investigate the diagnostic potential of 11C-acetate PET in the early detection of prostate cancer recurrence. A second aim was the evaluation of early and late PET in this context. The study population comprised 32 prostate cancer patients with early evidence of relapse after initial radiotherapy (group A) or radical surgery (group B). The median PSA of group A ( n=17) patients was 6 ng/ml (range 2.6–30.2) while that of group B ( n=15) was 0.4 ng/ml (range 0.08–4.8). Pelvic-abdominal-thoracic PET was started 2 min after injection of 11C-acetate and evaluated after fusion with CT. Group A: Taking a SUVmax≥2 as the cut-off, PET showed local recurrences in 14/17 patients and two equivocal results. Distant disease was observed in six patients and an equivocal result was obtained in one. Endorectal MRI was positive in 12/12 patients. Biopsy confirmed local recurrence in six of six (100%) patients. PET was positive in five of the six patients with biopsy-proven recurrences, the result in the remaining patient being equivocal. Group B: Among the 15 patients, visual interpretation was positive for local recurrences in five patients and equivocal in four. One obturator lymph node was positive. Endorectal MRI was positive in 11/15 patients and equivocal in two. Positional correlation of positive/equivocal results on PET and endorectal MRI was observed in seven of nine patients. PSA decreased significantly after salvage radiotherapy in 8/14 patients, providing strong evidence for local recurrence. PET of the eight patients responding to RT was positive in three and equivocal in two. 11C-acetate PET was found to be valuable in the early evaluation of prostate cancer relapse. Optimising scanning time and use of modern PET-CT equipment might allow further improvement. [ABSTRACT FROM AUTHOR]

Animal experiments have shown that short blocking of thymidine (dThd) synthesis with fluorodeoxyuridine (FdUrd) results in significantly increased DNA incorporation of [[sup 125]I]iododeoxyuridine ([[sup 125]I]IdUrd) in tumour and rapidly cycling tissues. Based on these results, we give an Auger and gamma radiation dosimetry estimate for a scintigraphy study in glioblastoma patients using [[sup 123]I]IdUrd. The Auger radiation dosimetry calculated for patients is based on measurement of DNA-incorporated [[sup 125]I]IdUrd in rapidly dividing tissues in nude mice xenografted with human glioblastoma. Further data obtained 0.5, 6 and 24 h after injection of [[sup 125]I]IdUrd allowed calculation of the additional gamma radiation exposure using MIRDOSE3.1. High gradients of radioactivity concentration between dividing and non-dividing tissues were observed 6 and 24 h after injection of [[sup 125]I]IdUrd combined with FdUrd pretreatment. While the estimated Auger radiation absorbed doses of [[sup 123]I]IdUrd in six rapidly cycling normal tissues in patients are low, the equivalent doses become significant with application of the recommended preliminary radiation weighting factor (W[sub R]) of 20 for stochastic effects of DNA-associated Auger radiation. Using the latter W[sub R], extrapolation of the animal results to the proposed patient injection with 300 MBq [[sup 123]I]IdUrd combined with FdUrd pretreatment indicates that the effective dose will be 5.42 mSv, including 1.67 mSv from Auger and 3.75 mSv from gamma radiation. The predicted Auger radiation effective dose for pa- tients undergoing [[sup 123]I]IdUrd scintigraphy will be significant if the enhancement of DNA incorporation that is achieved by means of FdUrd pretreatment is similar to that obtained in animals. [ABSTRACT FROM AUTHOR]

5-Iodo-2'-deoxyuridine (IdUrd), a thymidine (TdR) analogue, can be radiolabelled with iodine-125, an Auger radiation emitter, to provoke double-strand breaks once incorporated into DNA of cancer cells. We have previously shown that co-incubation of [[sup 125] I]IdUrd with unlabelled IdUrd provided an additive cytotoxicity in two human glioblastoma cell lines. This observation was unexpectedly correlated with an increase in the rate of DNA incorporation of [[sup 125] I]IdUrd. Here, we further evaluated the effects of unlabelled IdUrd on the uptake of [[sup 125] I]IdUrd in vitro and in vivo in mice xenografted with three human glioblastoma lines. The results showed that, in these three glioblastoma lines, unlabelled IdUrd increased the rate of uptake of [[sup 125] I]IdUrd in vitro by 2- to 4.4-fold and in vivo by 1.5- to 2.8-fold. The rate of uptake of [[sup 125] I]IdUrd in normal rapidly dividing tissues was also increased by 1.3- to 2.8-fold. TdR completely blocked [[sup 125] I]IdUrd uptake in tumours and tissues. Analogues of IdUrd, such as deoxyuridine and 5-iodo-1,3-dimethyuracil, did not reproduce the effect of IdUrd on the uptake of [[sup 125] I]IdUrd, suggesting that it is not related to protection against [[sup 125] I]IdUrd degradation. It is concluded that combined administration of unlabelled IdUrd may improve the use of radiolabelled IdUrd for cancer diagnosis or therapy. [ABSTRACT FROM AUTHOR]

In the etiological diagnosis of ACTH-dependent Cushing’s syndrome, it may be difficult to distinguish pituitary disease from ectopic ACTH production, specially when this is due to a benign neuroendocrine tumor. We describe a patient with partial dexamethasone suppression consistent with Cushing’s disease, an absent response to CRH suggesting ectopic ACTH production and an atypical, apparent circadian rhythm. Bilateral cavernous sinus catheterization suggested a nonpituitary source of ACTH and, in the search of an ectopic tumor, somatostatin receptor scintigraphy, abdominal CT scan, and duodenopancreatic endoscopic echography were performed and failed to reveal any abnormality. Thoracic CT scan disclosed a tiny right lung nodule that showed a definite tracer uptake on MIBG scintigraphy. After resection, the nodule proved to be an 8-mm typical pulmonary carcinoid, with positive immunostaining for the classical neuroendocrine markers and for ACTH, and showing tissue expression of the POMC gene. However, the CRH receptor gene was not expressed, explaining the absent CRH response in vivo, whereas the V3 vasopressin receptor gene was expressed in the tumor tissue. The latter feature appears to be characteristic of benign carcinoids and may contribute to explaining the CRH-independent circadian rhythm observed in this case. [ABSTRACT FROM AUTHOR]