Prognostic value of functional tumor burden on 68Ga-DOTATOC PET/CT in patients with pancreatic neuro-endocrine tumors.

Despite their relative quiescence, pancreatic neuro-endocrine tumors (pNET) can correspond to various presentations and outcomes. Several prognostic factors have been identified, including maximal standardized uptake value of the most intense focus (maxSUVmax) on Positron Emission Tomography (PET) with a somatostatin analogue. Herein, we investigate the prognostic value on progression free-survival of the total functional tumor volume (TFTV) measured by 68Ga-DOTATOC PET. From patients who underwent 68Ga-DOTATOC PET from 2008 to 2014, we selected consecutive patients with G1 or G2 pNET (2010 World Health Organization classification), at least one abnormal focus on PET and available follow-up data. TFTV was computed by summing the volumes of all pathological foci, delineated use of 41% of its SUVmax for each threshold focus. Fifty patients were included. During the follow-up period, 33 patients had stable or responsive disease (66%; median duration 28.5 months; range 6.3-77.7 months) and 17 patients experienced disease progression (34%; median progression time 21 months; range 6.7-44.7 months). Median PFS was 43.5 months. The best TFTV cut-off for predicting progression within 24 months was 13.8 cm3. Multivariate analysis determined that TFTV greater than 13.8 cm3 was the only criterion considered a significant risk factor for tumor progression (HR 2.9; p=0.0003). A significant difference in PFS was observed for TFTV (<13.8 vs. ≥ 13.8 cm3: median not reached vs. 25 months; p=0.0001). Our study suggests that 68Ga-DOTATOC TFTV measured on PET images is a valuable prognostic biomarker in patients with well-differentiated pNETs of all stages.

Mejor rendimiento de la PET/TC con 18F-FDOPA para la detección de metástasis de un tumor neuroendocrino del íleon / Best sensitivity of 18F-FDOPA PET/CT to detect metastasis in one case of neuroendocrine tumour of the ileum

Los tumores neuroendocrinos (TNE) son un grupo de tumores muy heterogéneos y de distribución variable, lo que dificulta su localización anatómica. En medicina nuclear, durante décadas se han propuesto diferentes técnicas de imagen PET o SPECT con diversos radiotrazadores para el estudio de estos tumores, no existiendo consenso actualmente sobre la más adecuada, incluso al considerar solamente los TNE digestivos. Presentamos el caso de una mujer de 67 años con un TNE bien diferenciado del íleon en la que se sospechó una recidiva y ninguna técnica de imagen fue capaz de detectar la enfermedad, excepto la PET/TC con 18F-FDOPA. El seguimiento posterior mostró progresión de la enfermedad, confirmándose la positividad de este primer hallazgo. A raíz del caso se discuten y comparan los radiofármacos posibles para el diagnóstico de TNE digestivos, haciendo énfasis en los derivados embriológicamente del intestino medio (AU)

Neuroendocrine tumours (NET) are heterogeneous and frequently spread over the body, making their imaging difficult. With this aim, nuclear medicine imaging, using PET or SPECT with different tracers, has been proposed for decades, but there is currently no consensus on the most appropriate technique, even when only considering gastrointestinal NET. The case is presented of a 67year old woman with a well differentiated NET of the ileum with suspected recurrence, which was not detected by any imaging technique except 18F-FDOPA PET/CT. Subsequent follow up showed disease progression, which confirmed the true positivity of 18F-FDOPA. Using this case, we discuss and compare different radiotracers for the diagnosis of gastrointestinal NET, focusing on those embryologically originating from the mid-gut (AU)

Best sensitivity of 18F-FDOPA PET/CT to detect metastasis in one case of neuroendocrine tumour of the ileum. / Mejor rendimiento de la PET/TC con 18F-FDOPA para la detección de metástasis de un tumor neuroendocrino del íleon.

Neuroendocrine tumours (NET) are heterogeneous and frequently spread over the body, making their imaging difficult. With this aim, nuclear medicine imaging, using PET or SPECT with different tracers, has been proposed for decades, but there is currently no consensus on the most appropriate technique, even when only considering gastrointestinal NET. The case is presented of a 67year old woman with a well differentiated NET of the ileum with suspected recurrence, which was not detected by any imaging technique except 18F-FDOPA PET/CT. Subsequent follow up showed disease progression, which confirmed the true positivity of 18F-FDOPA. Using this case, we discuss and compare different radiotracers for the diagnosis of gastrointestinal NET, focusing on those embryologically originating from the mid-gut.

Current applications of PET imaging of sex hormone receptors with a fluorinated analogue of estradiol or of testosterone.

Currently, the most frequent approach in the oncologic applications of positron emission tomography (PET) is detecting the hypermetabolic activity of the cancer tissue. A more specific approach, which may be complementary, is detecting the overexpression of receptors. In this review article, we aim to evaluate the results that are currently available for PET imaging of the sex hormone receptors in clinical oncology. The indication of PET and now PET/CT has been more disputed in breast carcinoma than in many other primary cancers (e.g., lung, head and neck, colorectal, lymphoma). 18F-fluorodeoxyglucose (FDG), the glucose analogue for PET imaging, has a limited sensitivity to detect the primary breast tumors in case of lobular or in situ forms or small sized tumors localised on systematic mammography, and to identify minimal node invasion in the axilla. Using 16α-[¹8F]fluoro-17ß-estradiol (FES), a fluorinated estradiol analogue, PET is able to detect the over-expression of the oestrogen receptor (ER) in lesions, at a whole-body level. FES and FDG appear complementary for a better diagnostic performance in staging locally advanced breast cancer or restaging recurrent or metastatic breast cancer. Another potential indication is predicting the response to starting or resuming hormone therapy in patients with metastatic breast cancer, in relation with the ER status of all lesions revealed by FES PET. In two retrospective studies, FDG PET was also able to predict the response to hormone therapy, on basis of a metabolic flare, observed either after 7-10 days of treatment or during an estradiol challenge. A prospective comparison of those approaches is warranted. One study reported predicting response to neoadjuvant chemotherapy thanks to a low value of FES SUV(max) or FES/FDG SUV(max) ratio. The presence of ER in uterine tumors, including the benign ones, in ovarian cancers or even in meningiomas, may have therapeutic consequences and FES PET could have a clinical utility in those settings; only initial results are available. The indication of PET and PET/CT has been even more disputed in prostate carcinoma, due to the lack of significant FDG uptake in most cases, at least before the castration-resistant stage. Using FDHT, a fluorinated testosterone analogue, PET is able to detect the over-expression of the androgen receptor (AR) in lesions, at a whole-body level. At least partly due to the rather large number of alternative tracers that are in development or even routinely available in some countries, few FDHT studies have been published until now. From absorbed dose values previously published for FES by the team of University of Washington School of Medicine at Seattle, and for FDHT by the teams of Memorial Sloan-Kettering Cancer Center at New York and of Washington University at St. Louis, we applied the coefficients of ICRP publication 103 and calculated an effective dose per unit of injected activity of 0.023 mSv/MBq for FES and 0.018 mSv/MBq for FDHT. The radiation exposure is of the same order of magnitude as with FDG.

(68)Ga-AMBA and (18)F-FDG for preclinical PET imaging of breast cancer: effect of tamoxifen treatment on tracer uptake by tumor.

INTRODUCTION: AMBA is a bombesin analogue that binds to GRPr. In a mouse model of estrogen-dependent human breast cancer, we tested whether (68)Ga-AMBA can be used for PET detection of GRPr-expressing tumors and could be more accurate than (18)F-FDG to monitor tumor response to hormone therapy. METHODS: The radiolabeling of (68)Ga-AMBA was automated using a R&D Synchrom module. ZR75-1, a breast cancer cell line, was xenografted in nude mice. (68)Ga-AMBA tumor uptake was compared with that of (18)F-FDG before and after treatment with tamoxifen. RESULTS: AMBA was (68)Ga-radiolabelled in 30min with 95.3% yield and purity≥98%. Prior to treatment, (68)Ga-AMBA was highly concentrated into tumors (tumor to non-tumor ratio=2.4 vs. 1.3 with (18)F-FDG). With tamoxifen treatment (n=6) (68)Ga-AMBA uptake plateaued after 1week and decreased after 2weeks, with a significant reduction compared to controls (n=4). In contrast the effect of tamoxifen treatment could not be appreciated using (18)F-FDG. CONCLUSIONS: (68)Ga-AMBA appeared better than (18)F-FDG to visualize and monitor the response to hormone treatment in this breast cancer model.

What is currently the best radiopharmaceutical for the hybrid PET/CT detection of recurrent medullary thyroid carcinoma?

Among thyroid malignancies, medullary thyroid carcinoma (MTC) has some very specific features. Production and secretion of large amounts of peptides occur in malignant transformed C cells with few exceptions, leading to high serum levels of calcitonin (Ctn) and carcinoembryonic antigen (CEA), that act after thyroidectomy as tumour markers warning for the presence of persistent or metastatic MTC. The availability of those serum biomarkers with an excellent sensitivity challenges medical imaging to localise the recurrent cancer tissue, since surgery is a major therapeutic option. The aims of this article are (i) to review literature evidence about the efficacy and tolerance of radiopharmaceuticals for 3 targets of PET/CT imaging (glucose metabolism, bioamines metabolism and somatostatin receptors) and also bone scintigraphy which is recommended in the Guidelines of European Society for Medical Oncology (ESMO; (ii) to compare the availability and the costs in relation with those radiopharmaceuticals, (iii) and to discuss a possible sequence of those examinations, in order to optimise spending and to minimise the overall radiation dose. In this context of recurrent MTC suspected on rising tumour markers levels after thyroidectomy, this survey of literature confirms that FDOPA is the best radiopharmaceutical for PET/CT with significant diagnostic performance if Ctn>150 pg/mL; an early image acquisition starting during the first 15 min is advised. In negative cases, FDG should be the next PET radiopharmaceutical, in particular if Ctn and CEA levels are rapidly rising, and PET with a somatostatin analogue labelled with gallium-68 when neither FDOPA nor FDG PET are conclusive. Bone scintigraphy could complement FDG-PET/CT if FDOPA is not available.

18-F fluorodeoxyglucose positron emission tomography indicating unsuspected infections in two patients with dermatomyositis.

Dermatomyositis is an idiopathic inflammatory myopathy that may be associated with malignancies. The technique of 18-F fluorodeoxyglucose (FDG)-positron emission tomography (PET) is an important tool to investigate underlying malignancy in patients with a possible paraneoplastic syndrome. We report two consecutive patients with dermatomyositis in whom 18-F FDG-PET revealed unsuspected infections. Physicians should be aware that a positive 18-F FDG-PET is not specific for malignancy and may reveal other conditions including an infectious disorder.

Prospective comparison of FDG and FET PET/CT in patients with head and neck squamous cell carcinoma.

AIM: The clinical usefulness of 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography (FDG-PET) in head and neck squamous cell carcinoma (HNSCC) is now well-documented. However, its sensitivity is greater than its specificity due to false-positive results in inflammatory or infectious lesions, which are frequent in this area, in particular after treatment by surgery and/or radiotherapy. O-2-fluoro-(18F)-ethyl-L-thyrosine (FET) has been reported not to be taken up by such lesions, and a preliminary study indicated that this may be clinically useful in HNSCC. We performed a prospective study to compare the diagnostic performances of FDG and FET PET/CT in the different settings of HNSCC. MATERIALS AND METHODS: Twenty-seven patients (20 men and seven women, aged 48-76, among 30 patients included) and 69 suspected cancer sites are now evaluable on basis of postsurgical histology and/or follow-up greater than 6 months; 15 patients were referred for initial staging and 12 during posttherapy follow-up, a recurrence being suspected in eight of them. FDG and FET PET/CT were performed on two different days, the patient fasting for 6 h, 1 h after injection of 5 MBq/kg of body mass of each radiopharmaceutical. Both PET/CT examinations were blind read more than 6 months after the end of inclusions in a random order for each tracer and with a time interval greater than 1 month between FDG and FET PET/CT blind readings. RESULTS: Overall diagnostic performances, derived from blind reading: FDG PET/CT on a per patient basis: sensitivity 100%, specificity 71%, accuracy 93%; FDG PET/CT on a per site basis: sensitivity 95%, specificity 63%, accuracy 83%; FET PET/CT on a per patient basis: sensitivity 70%, specificity 100%, accuracy 78%; FET PET/CT on a per site basis: sensitivity 64%, specificity 100%, accuracy 78%. At site level, sensitivity was significantly greater with FDG (p<0.02) and specificity with FET (p<0.01). The statistical level of significance was not reached at patient level. CONCLUSION: Although its good specificity was confirmed, FET did not appear to be suited as a first-line PET tracer in HNSCC imaging and cannot replace FDG for staging due to insufficient sensitivity. However, it was useful in a few selected cases to favor a wait and see attitude when a FDG+ FET- focus was discovered in patients referred for systematic FDG PET during follow-up. In contrast, second primary cancers should not be ruled out if FDG was clearly positive in the lungs or the digestive tract.

[Imaging and PET-CT of adult and childhood lymphoma]. / Imagerie radiologique et TEP scanner des lymphomes de l'adulte et de l'enfant.

Malignant lymphomas are lymphoproliferative disorders arising in both lymphoid tissue and non-lymphoid organ systems. Treatment rarely is surgical, and currently relies on a combination of chemotherapy and radiation therapy. The role of imaging is to determine the spread of the disease, to identify targets and to assess therapeutic response. Imaging techniques mainly use morphological criteria, and may underestimate infiltrative disease, as observed in bones. The frequent presence of residual masses after treatment usually prevents classification of patients as complete response. Over time, positron emission tomography (PET) with F18-fluorodeoxyglucose (FDG) has become a prominent part of the workup at diagnosis and during follow-up. Recently, PET has been integrated in the revised response criteria for malignant lymphoma.

Early detection of recurrence by 18FDG-PET in the follow-up of patients with colorectal cancer.

We assessed the potential benefits of including systematic 18fluorodeoxyglucose positron emission tomography (FDG-PET) for detecting tumour recurrence in a prospective randomised trial. Patients (N=130) who had undergone curative therapy were randomised to undergo either conventional (Con) or FDG-PET procedures during follow-up. The two groups were matched at baseline. Recurrence was confirmed histologically. 'Intention-to-treat' analysis revealed a recurrence in 46 patients (25 in the FDG-PET group, and 21 in the Con group; P=0.50), whereas per protocol analysis revealed a recurrence in 44 out of 125 patients (23 and 21, respectively; P=0.60). In another three cases, PET revealed unexpected tumours (one gastric GIST, two primary pulmonary cancers). Three false-positive cases of FDG-PET led to no beneficial procedures (two laparoscopies and one liver MRI that were normal). We failed to identify peritoneal carcinomatosis in two of the patients undergoing FDG-PET. The overall time in detecting a recurrence from the baseline was not significantly different in the two groups. However, recurrences were detected after a shorter time (12.1 vs 15.4 months; P=0.01) in the PET group, in which recurrences were also more frequently (10 vs two patients) cured by surgery (R0). Regular FDG-PET monitoring in the follow up of colorectal cancer patients may permit the earlier detection of recurrence, and influence therapy strategies.

Pathology underrates colon cancer extranodal and nodal metastases; ex vivo radioimmunodetection helps staging.

PURPOSE: Colorectal carcinoma is frequently accompanied by small lymph nodes metastases that often escape pathologic examination. We evaluated whether ex vivo radioimmunodetection with the Affinity Enhancement System (AES) could improve detection of mesocolonic metastases. EXPERIMENTAL DESIGN: A bivalent 111In-labeled hapten was injected (16 patients) 4 days after a bispecific antibody (anticarcinoembryonic antigen, antihapten). Surgery was done 1 to 3 days later, and radioactive uptake in the mesocolon was recorded. Extensive pathologic examination of the mesocolon (reference method) was done after fat dissolution. This method visualizes all lymph nodes but is not in routine use. RESULTS: The reference method disclosed 705 nodes. There was no significant difference between the number of node metastases detected by AES or by the reference method (16 versus 17). Better detection would have been obtained by AES than by routine pathology (P<0.01). In addition 12 extranodal metastases were found in this study of which eight were detected by AES. The prognostic importance of such extranodal metastases has been underlined in the literature. Routine pathology combined with AES would have disclosed all node metastases and 86% of total metastases versus 35% by routine pathology alone. CONCLUSIONS: Ex vivo radioimmunodetection could improve nodal and extranodal metastases detection in patients with colorectal cancer. Its value for improving pathologic analysis, together with the effect of these small metastases on prognosis, should be further evaluated. The benefit of adjuvant chemotherapy for patients upstaged with radioimmunodection should also be assessed because adjuvant chemotherapy improves the 5-year survival of stage III patients.

[18F-FDG PET and bone scintigraphy to search for bone metastasis of lung cancer]. / TEP au FDG-(18F) et scintigraphie du squelette dans la recherche de métastases osseuses du cancer broncho-pulmonaire.

Initial staging of lung cancer is essential to determine the appropriate therapeutic strategy. 18F-FDG PET is currently considered to be the gold standard. 99mTc bisphonate bone scintigraphy has long been indicated to search for bone metastases but it is not know whether this exploration adds further information after an 18F-FDG PET scan. In order to answer this question, two observers unaware of the clinical situation reread PET scans and bone scintigraphies and results compared with other imaging findings. Between February 2001 and March 2004, 39 patients (13F, 26M, 62 +/- 11 yr) underwent 18FFDG PET and bone scintigraphy (mean interval 17 +/- 17 d). When the two explorations agreed for the diagnosis of bone extension, we considered that bone scintigraphy added nothing. When the two explorations were in disagreement, the other imaging examinations, the clinical features and laboratory results during the five-month minimal follow-up were used to establish the reference diagnosis. 18F-FDG PET and bone scintigraphy were in agreement in 29 patients (74%) with positive results in 12 (31%) and negative results in 17 (43%). The two explorations were in disagreement in 10 patients (26%). Among the five disagreement cases with positive bone scintigraphy and no bone anomaly on the 18F-FDG PET, the anomalies were benign and explained by clinical features (3 patients) or were not confirmed by the clinical course and laboratory results (2 patients). Among the 5 cases with a bone anomaly on the 18F FDG PET, no metastasis could be identified during clinical follow-up. Bone scintigraphy does not enable identification of any bone metastases which were not recognized on the PET scan and therefore should not be performed systematically. Using a computed tomography scan with the 18F-FDG PET could further limit the contribution of bone scintigraphy by providing more precision concerning foci identified on the PET scan.

[Impact of computed tomography (CT) and 18F-deoxyglucose-coincidence detection emission tomography (FDG-CDET) image fusion for optimisation of conformal radiotherapy in non-small-cell lung cancers]. / Tomographie par émission de positons et détection en coïncidence (TEDC) et recalage d'images de simulation virtuelle par tomodensitométrie. Impact sur la planification de la radiothérapie conformationnelle des cancers bronchiques non à petites cellules.

UNLABELLED: To report a retrospective study concerning the impact of fused 18F-fluorodeoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and computed tomography (CT) images on three-dimensional conformal radiation therapy (3D-CRT) planning for patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred and one patients consecutively treated for stages I-III NSCLC were studied. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same radiation treatment position. Images were coregistered using five fiducial markers. Target volume delineation was initially performed on the CT images and the corresponding FDG-PET data were subsequently used as an overlay to the CT data to define target volume. RESULTS: FDG-PET identified previously undetected distant metastatic disease in 8 patients making them ineligible for curative CRT (one patient presented some positive uptakes corresponding to concomitant pulmonary tuberculosis). Another patient was ineligible for curative treatment because fused CT/PET images demonstrated excessively extensive intrathoracic disease. The gross tumor volume (GTV) was decreased by CT/PET image fusion in 21 patients (23%) and was increased in 24 patients (26%). The GTV reduction was > or = 25% in 7 patients because CT/PET image fusion reduced pulmonary GTV in 6 patients (3 patients with atelectasis) and mediastinal nodal GTV in 1 patient. The GTV increase was > or = 25% in 14 patients due to an increase of the pulmonary GTV in 11 patients (4 patients with atelectasis) and detection of occult mediastinal lymph node involvement in 3 patients. Among 81 patients receiving a total dose > or = 60 Gy at ICRU point, after CT/PET image fusion, the percentage of total lung volume receiving more than 20 Gy (VL20) increased in 15 cases and decreased in 22 cases. The percentage of total heart volume receiving more than 36 Gy increased in 8 patients and decreased in 14 patients. The spinal cord volume receiving at least 45 Gy (2 patients) decreased. After multivariate analysis, one single independent factor made significant effect of FDG/PET on the modification of the size of the GTV: tumor with atelectasis (P = 0.0001). Conclusion. - Our study confirms that integrated hybrid PET/CT in the treatment position and coregistered images have an impact on treatment planning and management of patients with NSCLC. FDG images using dedicated PET scanners with modern image fusion techniques and respiration-gated acquisition protocols could improve CT/PET image coregistration. However, prospective studies with histological correlation are necessary and the impact on treatment outcome remains to be demonstrated.

6-[F-18]fluoro-L-DOPA positron emission tomography in the imaging of Merkel cell carcinoma: preliminary report of three cases with 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography or pentetreotide-(111In) SPECT data.

PURPOSE: Merkel cell carcinoma (MCC) is an uncommon and aggressive cutaneous neoplasm of neuroendocrine origin. Somatostatin receptor scintigraphy (SRS) and positron emission tomography (PET) using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) have been proposed to stage MCC and to detect early recurrences. As 6-[F-18]fluoro-L-DOPA (FDOPA) is taken up by other neuroendocrine tumors, we speculated that FDOPA-PET could image MCC. PROCEDURE: FDOPA-PET was performed together with FDG-PET (three patients) and SRS (two patients) in different clinical settings: localization of the primary tumor, staging, and suspicion of recurrence. RESULTS: Uptake of FDOPA-(18F) by MCC was observed in the two true-positive cases, with an agreement between the results of FDOPA-PET, FDG-PET, and SRS; however, the contrast was lower on FDOPA-PET than on FDG-PET images. In the last patient suspected of recurrence repeatedly on SRS and with inconclusive FDG-PET, FDOPA-PET was negative, and a 12-month follow-up demonstrated a true-negative result. CONCLUSION: MCC takes up FDOPA-(18F). The potential role of FDOPA-PET in its management warrants clarification.

[Impact of computed tomography (CT) and 18F-deoxyglucose positron emission tomography (FDG-PET) image fusion for conformal radiotherapy in esophageal carcinoma]. / Tomographie par émission de positons et fusion d'images de simulation virtuelle par tomodensitométrie. Impact sur la planification de la radiothérapie conformationnelle des cancers de l'oesophage.

PURPOSE: To study the impact of fused (18)F-fluoro-deoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and computed tomography (CT) images on conformal radiation therapy (CRT) planning for patients with esophageal carcinoma. PATIENTS AND METHODS: Thirty-four patients with esophageal carcinoma were referred for concomitant radiotherapy and chemotherapy with radical intent. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same radiation treatment position. PET-images were coregistered using five fiducial markers. Target delineation was initially performed on CT images and the corresponding PET data were subsequently used as an overlay to CT data to define the target volume. RESULTS: FDG-PET identified previously undetected distant metastatic disease in 2 patients, making them ineligible for curative CRT. The Gross Tumor Volume (GTV) was decreased by CT and FDG image fusion in 12 patients (35%) and was increased in 7 patients (20.5%). The GTV reduction was >or=25% in 4 patients due to reduction of the length of the esophageal tumor. The GTV increase was >or=25% with FDG-PET in 2 patients due to the detection of occult mediastinal lymph node involvement in one patient and an increased length of the esophageal tumor in the other patient. Modifications of the GTV affected the planning treatment volume (PTV) in 18 patients. Modifications of delineation of GTV and displacement of the isocenter of PTV by FDG-PET also affected the percentage of total lung volume receiving more than 20 Gy (VL20) in 25 patients (74%), with a dose reduction in 12 patients and a dose increase in 13 patients. CONCLUSION: In our study, CT and FDG-PET image fusion appeared to have an impact on treatment planning and management of patients with esophageal carcinoma related to modifications of GTV. The impact on treatment outcome remains to be demonstrated.