Francesco Giammarile

FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0

The purpose of these guidelines is to assist physicians in recommending, performing, interpreting and reporting the results of FDG PET/CT for oncological imaging of adult patients. PET is a quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to maintain the accuracy and precision of quantitation. Repeatability and reproducibility are two essential requirements for any quantitative measurement and/or imaging biomarker. Repeatability relates to the uncertainty in obtaining the same result in the same patient when he or she is examined more than once on the same system. However, imaging biomarkers should also have adequate reproducibility, i.e. the ability to yield the same result in the same patient when that patient is examined on different systems and at different imaging sites. Adequate repeatability and reproducibility are essential for the clinical management of patients and the use of FDG PET/CT within multicentre trials. A common standardised imaging procedure will help promote the appropriate use of FDG PET/CT imaging and increase the value of publications and, therefore, their contribution to evidence-based medicine. Moreover, consistency in numerical values between platforms and institutes that acquire the data will potentially enhance the role of semiquantitative and quantitative image interpretation. Precision and accuracy are additionally important as FDG PET/CT is used to evaluate tumour response as well as for diagnosis, prognosis and staging. Therefore both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.

131I/123I-metaiodobenzylguanidine (mIBG) scintigraphy: procedure guidelines for tumour imaging.

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.

Clinical radionuclide therapy dosimetry: the quest for the "Holy Gray".

IntroductionRadionuclide therapy has distinct similarities to, but also profound differences from external radiotherapy.ReviewThis review discusses techniques and results of previously developed dosimetry methods in thyroid carcinoma, neuro-endocrine tumours, solid tumours and lymphoma. In each case, emphasis is placed on the level of evidence and practical applicability. Although dosimetry has been of enormous value in the preclinical phase of radiopharmaceutical development, its clinical use to optimise administered activity on an individual patient basis has been less evident. In phase I and II trials, dosimetry may be considered an inherent part of therapy to establish the maximum tolerated dose and dose-response relationship. To prove that dosimetry-based radionuclide therapy is of additional benefit over fixed dosing or dosing per kilogram body weight, prospective randomised phase III trials with appropriate end points have to be undertaken. Data in the literature which underscore the potential of dosimetry to avoid under- and overdosing and to standardise radionuclide therapy methods internationally are very scarce.DevelopmentsIn each section, particular developments and insights into these therapies are related to opportunities for dosimetry. The recent developments in PET and PET/CT imaging, including micro-devices for animal research, and molecular medicine provide major challenges for innovative therapy and dosimetry techniques. Furthermore, the increasing scientific interest in the radiobiological features specific to radionuclide therapy will advance our ability to administer this treatment modality optimally.

EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds

Primary liver cancers (i.e. hepatocellular carcinoma or cholangiocarcinoma) are worldwide some of the most frequent cancers, with rapidly fatal liver failure in a large majority of patients. Curative therapy consists of surgery (i.e. resection or liver transplantation), but only 10–20% of patients are candidates for this. In other patients, a variety of palliative treatments can be given, such as chemoembolization, radiofrequency ablation or recently introduced tyrosine kinase inhibitors, e.g. sorafenib. Colorectal cancer is the second most lethal cancer in Europe and liver metastases are prevalent either at diagnosis or in follow-up. These patients are usually treated by a sequence of surgery, chemotherapy and antibody therapy [Okuda et al. (Cancer 56:918–928, 1985); Schafer and Sorrell (Lancet 353:1253–1257, 1999); Leong et al. (Arnold, London, 1999)]. Radioembolization is an innovative therapeutic approach defined as the injection of micron-sized embolic particles loaded with a radioisotope by use of percutaneous intra-arterial techniques. Advantages of the use of these intra-arterial radioactive compounds are the ability to deliver high doses of radiation to small target volumes, the relatively low toxicity profile, the possibility to treat the whole liver including microscopic disease and the feasibility of combination with other therapy modalities. Disadvantages are mainly due to radioprotection constraints mainly for 131I-labelled agents, logistics and the possibility of inadvertent delivery or shunting [Novell et al. (Br J Surg 78:901–906, 1991)]. The Therapy, Oncology and Dosimetry Committees have worked together in order to revise the European Association of Nuclear Medicine (EANM) guidelines on the use of the radiopharmaceutical 131I-Lipiodol (Lipiocis®, IBA, Brussels, Belgium) and include the newer medical devices with 90Y-microspheres. 90Y is either bound to resin (SIR-Spheres®, Sirtex Medical, Lane Cove, Australia) or embedded in a glass matrix (TheraSphere®, MDS Nordion, Kanata, ON, Canada). Since 90Y-microspheres are not metabolized, they are not registered as unsealed sources. However, the microspheres are delivered in aqueous solution: radioactive contamination is a concern and microspheres should be handled, like other radiopharmaceuticals, as open sources. The purpose of this guideline is to assist the nuclear medicine physician in treating and managing patients undergoing such treatment.

EANM procedure guideline for treatment of refractory metastatic bone pain

IntroductionBone pain is a common symptom of metastatic disease in cancer, experienced with various intensities by about 30% of cancer patients, during the development of their disease, up to 60–90% in the latest phases.DiscussionIn addition to other therapies, such as analgesics, bisphosphonates, chemotherapy, hormonal therapy and external beam radiotherapy, bone-seeking radiopharmaceuticals are also used for the palliation of pain from bone metastases. Substantial advantages of bone palliation radionuclide therapy include the ability to simultaneously treat multiple sites of disease with a more probable therapeutic effect in earlier phases of metastatic disease, the ease of administration, the repeatability and the potential integration with the other treatments.ConclusionThe Therapy, Oncology and Dosimetry Committees have worked together to revise the EANM guidelines on the use of bone-seeking radiopharmaceuticals. The purpose of this guideline is to assist the nuclear medicine physician in treating and managing patients undergoing such treatment.

EANM procedure guidelines for 131I-meta-iodobenzylguanidine (131I-mIBG) therapy

Meta-iodobenzylguanidine, or Iobenguane, is an aralkylguanidine resulting from the combination of the benzyl group of bretylium and the guanidine group of guanethidine (an adrenergic neurone blocker). It is a noradrenaline (norepinephrine) analogue and so-called “false” neurotransmitter. This radiopharmaceutical, labeled with 131I, could be used as a radiotherapeutic metabolic agent in neuroectodermal tumours, that are derived from the primitive neural crest which develops to form the sympathetic nervous system. The neuroendocrine system is derived from a family of cells originating in the neural crest, characterized by an ability to incorporate amine precursors with subsequent decarboxylation. The purpose of this guideline is to assist nuclear medicine practitioners to evaluate patients who might be candidates for 131I-meta-iodobenzylguanidine to treat neuro-ectodermal tumours, to provide information for performing this treatment and to understand and evaluate the consequences of therapy.

Phase II Study of Temozolomide in Relapsed or Refractory High-Risk Neuroblastoma: A Joint Société Française des Cancers de l’Enfant and United Kingdom Children Cancer Study Group–New Agents Group Study

PURPOSE To determine the response rate (RR) of neuroblastoma (NB) in children to temozolomide (TMZ), and evaluate the duration of response and tolerance of the drug in this patient population. PATIENTS AND METHODS A multicenter, phase II evaluation of an oral, daily schedule of TMZ (200 mg/m2/d x 5 days every 28 days) was undertaken in children with refractory or relapsed high-risk NB (metastatic or localized with Myc-N amplification). Response assessment was based on imaging with two-dimentional measurement of disease and meta-iodobenzylguanidine (MIBG) score. Activity was defined by a reduction in lesion size or isotope uptake at anytime. Methodology included a two-step design using Flemings method with a first step of 15 patients and a second of 10 additional patients if two to four responses had been observed in the first cohort. All data was centrally reviewed by a panel. RESULTS Twenty-five assessable patients were recruited over a 14-month period in 14 centers and received 94 cycles of chemotherapy. Twenty-three patients had metastatic NB either refractory (n = 9) or in relapse (n = 14). Grade 3 or 4 thrombocytopenia was the most frequent toxicity (16% of cycles). Myelosuppression resulted in treatment delays and dose reductions (24% and 21% of cycles, respectively). Response (complete response, very good partial response, or partial response) was observed in five patients (RR = 20% +/- 8%) with a median duration of 6 months and an objective or mixed response in five additional patients. CONCLUSION Temozolomide shows activity in heavily pretreated patients with NB, and deserves further evaluation in combination with another drug.

EANM procedure guideline for radio-immunotherapy for B-cell lymphoma with (90)Y-radiolabelled ibritumomab tiuxetan (Zevalin).

BackgroundIn January 2004, EMEA approved 90Y-radiolabelled ibritumomab tiuxetan, Zevalin, in Europe for the treatment of adult patients with rituximab-relapsed or -refractory CD20+ follicular B-cell non-Hodgkin’s lymphoma. The number of European nuclear medicine departments using Zevalin is continuously increasing, since the therapy is often considered successful. The Therapy, Oncology and Dosimetry Committees have worked together in order to define some EANM guidelines on the use of Zevalin, paying particular attention to the problems related to nuclear medicine.PurposeThe purpose of this guideline is to assist the nuclear medicine physician in treating and managing patients who may be candidates for radio-immunotherapy. The guideline also stresses the need for close collaboration with the physician(s) treating the patient for the underlying disease.

High and Low Grade Oligodendrogliomas (ODG): Correlation of Amino-Acid and Glucose Uptakes Using PET and Histological Classifications

Classification and treatment strategy of Oligodendrogliomas (ODG) remain controversial. Imaging relies essentially on contrast enhancement using CT or MRI. The aim of our study was to use positron emission tomography (PET) using [18F]-flurodeoxyglucose (FDG) and [11C]-L-methyl-methionine (MET) to evaluate metabolic characteristics of (ODG). We studied 19 patients with proven ODG, comparing standardised uptake values (SUV) and maximal tumor/contralateral normal tissues ratios (T/N). Imaging findings were compared with WHO, Smith and Daumas—Duport classifications. Uptake of FDG was decreased only in 8 patients, independently of grading, while MET uptake was always increased. MET uptake was significantly higher for high grade tumors grouped according to Smith or Daumas—Duport classifications, while no significant difference in MET uptake was found when using WHO classification. A different correlation was found between FDG and MET uptakes in normal tissues and high grade tumors. A trend for improved progression free survival was found for tumors that lacked contrast enhancement on MRI or those showing low FDG or MET uptake.In conclusion, MET appeared more sensitive than FDG to detect proliferation in ODG. The preferential protein metabolism, already noticeable for low-grade tumor, correlated with glucose metabolism and helped to separate, in vivo, high and low grade tumors.

Additional Benefit of F-18 FDG PET/CT in the staging and follow-up of pediatric rhabdomyosarcoma.

Purpose: The therapeutic management of rhabdomyosarcoma (RMS) is strongly dependent on initial staging. This study aimed to evaluate F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) as an adjunct to conventional imaging (CI) in the staging and follow-up of pediatric RMS. Materials and Methods: A total of 13 consecutive children and adolescents (12 males, 1 female; mean age, 9.6 years) with histologically proven RMS (10 alveolar, 3 embryonal), in whom FDG PET/CT was performed at staging and follow-up, were retrospectively included. In total, 35 FDG PET/CT were compared with CI (MRI, CT, and bone scintigraphy) performed with a less than a 15-day interval. Histologic data, follow-up (mean, 27 months), and the final judgment of a multidisciplinary tumor board were considered as the standard of reference for result interpretation. Results: At staging, FDG PET/CT revealed 1 RMS of the prostate missed by CI, and found 19 true-positive lymph node territories in 4 patients and 11 bone metastases in 3 patients, versus 12 and 3, respectively, with CI. Conversely, FDG PET/CT was less sensitive for detecting infracentimetric lung nodules in 1 patient. On the whole analysis, FDG PET/CT modified lymph node staging in 4 of 13 patients, bone involvement in 2 patients, and led to treatment alteration in 2 children. Conclusions: FDG PET/CT can be useful in staging and restaging pediatric RMS, especially for assessing lymph nodes and bone involvement, and for detecting unknown primary sites of RMS, with potential therapeutic strategy alteration.