PET/TC con FDG y nuevos radiofármacos en pacientes con mieloma múltiple / FDG-PET/CT and new radiopharmaceuticals in patients with multiple myeloma

El mieloma múltiple es un trastorno proliferativo clonal de células plasmáticas, dentro del grupo de las gammapatías monoclonales, que producen una proteína llamada M o proteína de mieloma, generalmente IgG o IgA, en la médula ósea. Supone el 1% en las estadísticas generales del cáncer y el 13% en las series de neoplasias hematológicas, con una incidencia acumulada en España de aproximadamente 5 personas por 100.000 habitantes-año. Dicha incidencia aumenta con la edad, de forma que el 50% de los casos se diagnostican en pacientes de edades superiores a 75años, siendo infrecuente en la población menor de 40años. En esta publicación se detallan las indicaciones de la PET/TC con FDG para el diagnóstico de extensión y la valoración de respuesta en pacientes con mieloma múltiple, aceptadas por el grupo internacional de trabajo en mieloma, así como nuevos radiofármacos de imagen molecular con valor potencial para una medicina personalizada (AU)

Multiple myeloma is a monoclonal gammopathy, a clonal proliferative disorder of plasma cells that produces a protein called M or myeloma protein in the bone marrow, usually IgG or IgA. It accounts for 1% in the general cancer statistics and represents 10% of all hematologic tumours, with a cumulative incidence in Spain of about 5/100,000/year. The incidence increases with age, so that 50% of cases are diagnosed in patients over 75years of age, being infrequent in the population under 40years of age. This publication details the indications of FDG PET/CT for the staging and response assessment in patients with MM, accepted by the international working group on myeloma, as well as new molecular imaging radiopharmaceuticals with potential value for personalised medicine (AU)

Diagnostic accuracy of visual analysis versus dual time-point imaging with 18F-FDG PET/CT for the characterization of indeterminate pulmonary nodules with low uptake. / Precisión diagnóstica del análisis visual frente al protocolo de imagen tardía con 18F-FDG PET/TC para la caracterización de nódulos pulmonares indeterminados con baja captación.

OBJECTIVE: To determine the accuracy of visual analysis and the retention index (RI) with dual-time point 18F-FDG PET/CT for the characterization of indeterminate pulmonary nodules (IPN) with low FDG uptake. MATERIALS AND METHODS: A retrospective analysis was performed on 43 patients (28 men, 64 ± 11 years old, range 36-83 years) referred for IPN characterization with 18F-FDG-PET/CT and maximum standard uptake value ≤ 2.5 at 60 minutes post-injection (SUVmax1). Nodules were analyzed by size, visual score for FDG uptake on standard (OSEM 2,8) and high definition (HD) reconstructions, SUVmax1, SUVmax at 180 minutes post-injection (SUVmax2), and RI was calculated. The definitive diagnosis was based on histopathological confirmation (n = 28) or ≥ 2 years of follow-up. RESULTS: Twenty-four (56%) nodules were malignant. RI ≥ 10% on standard reconstruction detected 18 nodules that would have been considered negative using the standard SUVmax ≥ 2.5 criterion for malignancy. RI ≥ 10% had a sensitivity, specificity, PPV, NPV and accuracy of 75, 73.7, 78.3, 70, and 74.4%, respectively, while for FDG uptake > liver on HD these were 79.1, 63.2, 73.1, 70.6, and 72.1%, respectively. SUVmax1 ≥ 2, SUVmax2 > 2.5 and FDG uptake > liver on standard reconstruction had a PPV of 100%. FDG uptake > mediastinum on HD had a NPV of 100%. CONCLUSIONS: RI ≥ 10% was the most accurate criterion for malignancy, followed by FDG uptake > liver on HD reconstruction. On standard reconstruction, SUVmax1 ≥2 was highly predictive of malignancy, as well as SUVmax2 > 2.5 and FDG uptake > liver. FDG uptake < mediastinum on HD was highly predictive of benign nodules.

Immunotherapy, cancer and PET. / Inmunoterapia, cáncer y PET.

The treatment of cancer by immunotherapy has been a revolution, as it is the first strategy that manages to control the disease for prolonged periods of time. Its efficacy is associated with different imaging response patterns and the appearance of new toxicities. We would highlight two patterns of tumour response: pseudoprogression, or growth of tumour lesions after the start of immunotherapy treatment, followed by a significant reduction in lesions, and hyperprogression, acceleration of tumour progression and metastasis early after the start of treatment. The emergence of such patterns has generated new metabolic response criteria, such as PECRIT, PERCIMT, imPERCIST and IPERCIST. Of particular interest are the new immunoPET-specific biomarkers, as they allow the identification of patients presenting the tumour target and are useful for predicting response to immunotherapy.

A multidisciplinary consensus on the morphological and functional responses to immunotherapy treatment

The implementation of immunotherapy has radically changed the treatment of oncological patients. Currently, immunotherapy is indicated in the treatment of patients with head and neck tumors, melanoma, lung cancer, bladder tumors, colon cancer, cervical cancer, breast cancer, Merkel cell carcinoma, liver cancer, leukemia and lymphomas. However, its efficacy is restricted to a limited number of cases. The challenge is, therefore, to identify which subset of patients would benefit from immunotherapy. To this end, the establishment of immunotherapy response criteria and predictive and prognostic biomarkers is of paramount interest. In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues (AU)

A multidisciplinary consensus on the morphological and functional responses to immunotherapy treatment.

The implementation of immunotherapy has radically changed the treatment of oncological patients. Currently, immunotherapy is indicated in the treatment of patients with head and neck tumors, melanoma, lung cancer, bladder tumors, colon cancer, cervical cancer, breast cancer, Merkel cell carcinoma, liver cancer, leukemia and lymphomas. However, its efficacy is restricted to a limited number of cases. The challenge is, therefore, to identify which subset of patients would benefit from immunotherapy. To this end, the establishment of immunotherapy response criteria and predictive and prognostic biomarkers is of paramount interest. In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues.

FDG PET/CT in colorectal cancer. / FDG PET/TC en el cáncer colorrectal.

Colorectal cancer is the third most frequent cancer worldwide. Although its incidence is increasing, mainly in those aged under50, mortality has decreased by 50% in the more developed countries, principally due to the adoption of new practices in prevention, diagnosis and treatment. In particular, the various diagnostic imaging modalities allow improved therapeutic decision-making, evaluation of the response and early detection of recurrence. The aim of this paper is to review the available scientific evidence on the value of positron emission tomography with 18F-FDG (18F-FDG PET/CT) in the colorectal cancer, with special emphasis on the indications of the guidelines and recommendations of the main international scientific associations regarding this imaging technique.

18F-FDG PET/CT in locally advanced cervical cancer: A review. / PET/TC con 18F-FDG en cáncer de cérvix localmente avanzado.

Cervical cancer is the second most common gynecological cancer worldwide. In locally advanced cervical cancer, 18F-FDG PET/CT has become important in the initial staging, particularly in the detection of nodal and distant metastasis, aspects with treatment implications and prognostic value. The aims of this study were to review the role of 18F-FDG PET/CT in uterine cervical cancer, according to the guidelines of the main scientific institutions (FIGO, NCCN, SEGO, SEOM, ESGO, and ESMO) and its diagnostic accuracy compared to conventional radiological techniques, as well as to review the acquisition protocol and its utility in radiotherapy planning, response assessment and detection of recurrence.

Radium-223 in the treatment of bone metastasis in patients with castration-resistant prostate cancer. Review and procedure. / Radio-223 en el tratamiento de metástasis óseas en pacientes con cáncer de próstata resistente a la castración. Revisión de la literatura y procedimiento.

Bone metastatic disease is the main cause of morbidity / mortality in patients with prostate cancer, presenting frequently as bone pain, pathological fractures or spinal cord compression, which requires early and timely therapy. Although, for the moment, the therapeutic window for its use has not been definitively established, radium-223 (223Ra), an alpha particle emitter, has proved to be an effective therapeutic tool, pre or post-chemotherapy, in patients with castration-resistant prostate cancer with symptomatic bone metastases and absence of visceral metastases, significantly modifying the prognosis of the disease. It is therefore imperative to define the ideal scenarios and the correct protocol for the use of this therapy and thus offer the greatest possible clinical benefit to the patient.

68Ga-PSMA PET/CT in prostate cancer. / La PET/TC con 68Ga-PSMA en el cáncer de próstata.

Positron emission tomography/computed tomography (PET/CT) with 68Ga-PSMA is a non-invasive diagnostic technique to image prostate cancer with increased prostate-specific membrane antigen (PSMA) expression. PSMA is a transmembrane protein present in all prostatic tissues. Increased PSMA expression is seen in several malignancies, although prostate cancer is the tumour where it presents higher concentrations. Almost all prostate adenocarcinomas show PSMA expression in most of lesions, primary and metastatic. Immunohistochemistry has demonstrated that the expression of PSMA increases in patients with de-differentiated, metastatic or hormone-refractory tumours. Moreover, the expression level of PSMA has a prognostic value for disease outcome. PET measures the three-dimensional distribution of 68Ga-PSMA, producing semi-quantitative images that allow for non-invasive assessment of PSMA expression.

Impact of initial FDG PET/CT in the management plan of patients with locally advanced head and neck cancer.

OBJECTIVE: To determine the impact of initial FDG PET/CT staging on clinical stage and the management plan in patients with locally advanced head and neck cancer (LAHNC). MATERIALS AND METHODS: We retrospectively reviewed the records of 72 consecutive patients (2007-2010) staged with PET/CT and conventional CT with tumours of hypopharynx/larynx (26 patients, 36 %), oral cavity (17 patients, 24 %), oropharynx (16 patients, 22 %), nasopharynx (12 patients, 17 %), and others (2 %). The impact of PET/CT on management plans was considered high when PET/CT changed the planned treatment modality or treatment intent, and intramodality changes were considered as minor changes with low impact. RESULTS: FDG PET/CT changed the stage in 27 patients and had high impact on the management plan in 12 % of patients (detection of distant metastases in 6 patients and stage II in 2 patients). Intramodality changes were more frequent: FDG PET/CT altered the TNM stage in 18/72 (25 %) of patients, upstaging N stage in 90 % of patients with low impact. CONCLUSIONS: Initial FDG PET/CT staging not only improves stage but also affects the management plan in LAHNC patients.

[¹8F]fluorothymidine-positron emission tomography in patients with locally advanced breast cancer under bevacizumab treatment: usefulness of different quantitative methods of tumor proliferation.

OBJECTIVES: To investigate quantitative methods of tumor proliferation using 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT) PET in patients with breast cancer (BC), studied before and after one bevacizumab administration, and to correlate the [(18)F]FLT-PET uptake with the Ki67 index. MATERIAL AND METHODS: Thirty patients with newly diagnosed, untreated BC underwent a [(18)F]FLT-PET before and 14 days after bevacizumab treatment. A dynamic scan centered over the tumor began simultaneously with the injection of [(18)F]FLT (385 ± 56 MBq). Image derived input functions were obtained using regions of interest drawn on the left ventricle (LV) and descending aorta (DA). Metabolite corrected blood curves were used as input functions to obtain the kinetic Ki constant using the Patlak graphical analysis (time interval 10-60 min after injection). Maximum SUV values were derived for the intervals 40-60 min (SUV40) and 50-60 min (SUV50). PET parameters were correlated with the Ki67 index obtained staining tumor biopsies. RESULTS: [(18)F]FLT uptake parameters decreased significantly (p<0.001) after treatment: SUV50=3.09 ± 1.21 vs 2.22 ± 0.96; SUV40=3.00 ± 1.18 vs 2.14 ± 0.95, Ki_LV(10-3)=52[22-116] vs 38[13-80] and Ki_DA(10-3)=49[15-129] vs 33[11-98]. Consistency interclass correlation coefficients within SUV and within Ki were high. Changes of SUV50 and Ki_DA between baseline PET and after one bevacizumab dose PET correlated with changes in Ki67 index (r-Pearson=0.35 and 0.26, p=0.06 and 0.16, respectively). CONCLUSIONS: [(18)F]FLT-PET is useful to demonstrate proliferative changes after a dose of bevacizumab in patients with BC. Quantification of tumor proliferation by means of SUV and Ki has shown similar results, but SUV50 obtained better results. A correlation between [(18)F]FLT changes and Ki67 index was observed.

[Validation of segmentation techniques for positron emission tomography using ex-vivo images of oncological surgical specimens]. / Validación de técnicas de segmentación para la tomografía por emisión de positrones mediante imágenes ex-vivo de piezas quirúrgicas oncológicas.

OBJECTIVE: To design a novel ex-vivo acquisition technique to establish a common framework to validate different segmentation techniques for oncological PET images. To evaluate several automatic segmentation algorithms on this set of images. MATERIAL AND METHODS: In 15 patients with cancer, ex-vivo PET studies of surgical specimens removed during surgery were performed after injection of (18)F-FDG. Images were acquired in two scanners: a clinical PET/CT and a high-resolution PET scanner. Real tumor volume was determined in each patient, and a reference image was generated for segmentation of each tumor. Images were segmented with 12 automatic algorithms and with a standard method for PET (relative threshold at 42%) and results were evaluated by quantitative parameters. RESULTS: It has been possible to demonstrate by segmentation of PET images of surgical specimens that on high resolution PET images, 8 out of 12 evaluated segmentation techniques outperformed the standard method, whose value is 42%. However, none of the algorithms outperformed the standard method when applied on images from the clinical PET/CT. Due to the great interest of this set of PET images, all studies have been published on the Internet in order to provide a common framework for validation and comparison of different segmentation techniques. CONCLUSIONS: We have proposed a novel technique to validate segmentation techniques for oncological PET images, acquiring ex-vivo PET studies of surgical specimens. We have demonstrated the usefulness of this set of PET images by evaluating several automatic segmentation algorithms.

[Contribution of time of flight and point spread function modeling to the performance characteristics of the PET/CT Biograph mCT scanner]. / Aportación del tiempo de vuelo y de la modelización de la respuesta a una fuente puntual a las características de funcionamiento del tomógrafo PET/TAC Biograph mCT.

OBJECTIVE: To characterize the performance of the Biograph mCT PET/CT TrueV scanner with time of flight (TOF) and point spread function (PSF) modeling. MATERIAL AND METHODS: The PET/CT scanner combines a 64-slice CT and PET scanner that incorporates in the reconstruction the TOF and PSF information. PET operating characteristics were evaluated according to the standard NEMA NU 2-2007, expanding some tests. In addition, different reconstruction algorithms were included, and the intrinsic radiation and tomographic uniformity were also evaluated. RESULTS: The spatial resolution (FWHM) at 1 and 10cm was 4.4 and 5.3mm, improving to 2.6 and 2.5mm when PSF is introduced. Sensitivity was 10.9 and 10.2 Kcps/MBq at 0 and 10cm from the axis. Scatter fraction was less than 34% at low concentrations and the noise equivalent count rate (NECR) was maximal at 27.8 kBq/mL with 182 Kcps, the intrinsic radiation produced a rate of 4.42 true coincidences per second. Coefficient of variation of the volume and system uniformity were 4.7 and 0.8% respectively. The image quality test showed better results when PSF and TOF were included together. PSF improved the hot spheres contrast and background variability, while TOF improved the cold spheres contrast. CONCLUSIONS: The Biograph mCT TrueV scanner has good performance characteristics. The image quality improves when the information from the PSF and the TOF is incorporated in the reconstruction.

Mimotopes of mutalysin-II from Lachesis muta snake venom induce hemorrhage inhibitory antibodies upon vaccination of rabbits.

Mutalysin-II (mut-II) from Lachesis muta snake venom is an endopeptidase with hemorrhagic activity. A mAb against mutalysin-II that neutralized the hemorrhagic effect was produced previously. To identify the mAb epitopes, sets of 15-mer overlapping peptides covering the mut-II amino acid sequence were synthesized using the SPOT method and tested but failed to react with the mAb. Using a phage-display approach seventeen clones reactive with mAb were identified. Additional immunoassays with the peptides and mAb identified the QCTMDQGRLRCR, TCATDQGRLRCT, HCFHDQGRVRCA, HCTMDQGRLRCR and SCMLDQGRSRCR sequences as possible epitopes. Immunization of rabbits with these peptides induced antibodies that recognize mut-II and protected against the hemorrhagic effects of Lachesis venom.

Evaluation of spatial resolution of a PET scanner through the simulation and experimental measurement of the recovery coefficient.

PURPOSE: In order to measure spatial resolution of a PET tomograph in clinical conditions, this study describes and validates a method based on the recovery coefficient, a factor required to compensate underestimation in measured radioactivity concentration for small structures. METHODS: In a PET image, the recovery factors of radioactive spheres were measured and their comparison with simulated recovery coefficients yielded the tomographic spatial resolution. Following this methodology, resolution was determined in different surrounding media and several conditions for reconstruction, including clinical conditions for brain PET studies. All spatial resolution values were compared with those obtained using classical methods with point and line sources. RESULTS: In each considered condition, spatial resolution of the PET image estimated using the recovery coefficient showed good agreement with classical methods measurements, validating the procedure. CONCLUSION: Measurement of the recovery coefficient provides an assessment of tomographic spatial resolution, particularly in clinical studies conditions.