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.

Fluorocholine (18F) and sodium fluoride (18F) PET/CT in the detection of prostate cancer: prospective comparison of diagnostic performance determined by masked reading.

AIM: The aim of this paper was to compare the diagnostic performance of positron emission tomography/computed tomography (PET/CT) with fluorocholine (18F) (FCH) or fluoride(18F) (FNa) for the detection of bone metastasis in patients with prostate cancer complaining from osteoarticular pain, taking into account whether they were referred for initial staging or recurrence localization. The initial hypothesis was that FCH site-based specificity would be superior to that of F Na, with no loss in sensitivity. METHODS: Forty-two patients were enrolled in this prospective study, underwent both PET/CTs and were then followed-up for at least 6 months. The standard of truth (SOT) about the presence/absence and location of bone metastasis could be determined in 40 patients, by 2 independent medical assessors, blinded to the results of both PET/CTs. The comparison was performed according to the guideline of the European Medicines Agency, i.e. based on the results of blind reading with SOT as reference. RESULTS: Bone extension was present in 22 patients and absent in 18. Patient-based performance for FCH vs. FNa was 91% vs. 91% for sensitivity, 89% vs. 83% for specificity and 90% vs. 88% for accuracy (no significant difference). Of 360 skeletal sites, 68 were malignant and 292 non-invaded. There was no significant difference in site-based performance in the group of patients referred at initial staging, but in the group of patients referred for suspicion of recurrence, FCH was significantly more specific than FNa (96% vs. 91%, P=0.033 with Obuchowski's correction) while sensitivity was the same, 89%. CONCLUSION: Both radiopharmaceuticals, based on a very different metabolic approach, showed good diagnostic performance. If FCH is available, it should be preferred in patients after initial treatment.

[Fluoroethylthyrosine 18F PET in the detection of brain tumours]. / TEP à la fluoroéthyltyrosine (18F) pour la détection des tumeurs cérébrales.

UNLABELLED: PET with fluoroethylthyrosine (FET), amino-acid analogue, has been performed in Germany since the beginning of the decade for molecular and metabolic imaging of brain tumours, since FDG, the glucose analogue which is the reference tracer for clinical PET, has this drawback to be taken-up intensely by cerebral cortex. We report on our preliminary results on the comparison of PET/CT with FET and FDG in 10 evaluable patients presenting with a brain lesion either at diagnosis or after treatment. In an attempt to optimise specificity, FET PET/CT has been acquired as a static image 1h after injection, while the most current practice is a dynamic 40 min acquisition starting at FET injection. With our acquisition protocol, diagnostic performance of FET was 88% sensitivity and 80% accuracy vs 13% and 30% respectively for FDG. CONCLUSION: FET is a radiopharmaceutical with clinical usefulness for the diagnosis, delineation and monitoring of brain tumours. Association with FDG allows identification of high-grade lesions or components, but it could be avoided providing that acquisition and quantification procedures of FET PET/CT would have been better optimised and standardised.

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.

MRI and FDG PET/CT findings in a case of probable Heidenhain variant Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is a neurodegenerative disease caused by the accumulation of a pathogenic isoform of a prion protein in neurons that is responsible for subacute dementia. The Heidenhain variant is an atypical form of CJD in which visual signs are predominant. This is a report of the case of a 65-year-old man with probable CJD of the Heidenhain variant, with topographical concordance between findings on magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (FDG) photopenic areas on positron emission tomography (PET)/computed tomography (CT) for cortical parietooccipital lesions.

[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.

The sentinel lymph node procedure for patients with preoperative diagnosis of ductal carcinoma in situ: risk factors for unsuspected invasive disease and for metastatic sentinel lymph nodes.

BACKGROUND: Occult invasive disease could be found at definitive histology in patients initially diagnosed with large ductal carcinoma in situ (DCIS). Sentinel lymph node (SLN) biopsy is a reliable and minimally invasive procedure providing axillary information and avoiding a second operation in this particular group of patients. The aim of our study was to assess the value of SLN biopsy in patients with large DCIS who are at highest risk for being upstaged to invasive carcinoma. PATIENTS AND METHODS: The study included 195 patients diagnosed with DCIS upon initial core biopsy and undergoing SLN biopsy. Many features were correlated with the presence of unsuspected invasive disease and positive SLN biopsy using univariate and multivariate analyses. RESULTS: Of the 110 patients with pure DCIS, seven patients (6%) had a metastatic lymph node; 31 patients (16%) were found to have invasive disease upon final histology. Univariate analysis of predictors of unsuspected invasive carcinoma showed that patients having a preoperative biopsy that indicated DCIS with microinvasion (DCISM) or large DCIS were at a higher risk of invasive carcinoma after histological examination of the operative specimen. Of the 31 patients who were upstaged to invasive carcinoma at final histology, seven patients (22%) had a positive SLN biopsy. The analysis of predictors of positive SLN in our study shows that diffuse DCIS requiring mastectomy is the main risk factor for SLN metastasis. CONCLUSION: There are no real predictive factors for invasive disease in patients with an initial diagnosis of DCIS or DCISM. Our study supports the value of SLN biopsy in patients with a preoperative DCISM biopsy or patients with a large pure DCIS biopsy requiring mastectomy.

Impact of [18F]-fluorodeoxyglucose ([18F]-FDG) imaging in sarcoidosis: unsuspected neurosarcoidosis discovered by [18F]-FDG PET and early metabolic response to corticosteroid therapy.

A 46-year-old woman, with biopsy proven pulmonary sarcoidosis, was referred for an [18F]-FDG PET/CT scan that depicted multivisceral involvement and an unusual [18F]-FDG focus located in the pituitary fossa consistent with pituitary sarcoidosis. This was confirmed by decreased antidiuretic hormone blood levels and contrast-enhanced CT scan. This unsuspected neurosarcoidosis prompted corticosteroid therapy. A [18F]-FDG-PET/CT examination performed 10 weeks after initiation of treatment revealed complete recovery. It is suggested that the skull base should be included in the PET scanning of patients with sarcoidosis. [18F]-FDG imaging may be useful in the early evaluation of response to treatment.

[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.

[Assessment of tumor radiosensitivity using functional and metabolic nuclear imaging in research and clinical practice. A review]. / Evaluation de la radiosensibilité tumorale par l'imagerie fonctionnelle et métabolique : de la recherche à l'application clinique. Revue de la littérature.

During the last half of century considerable research on radiosensitivity biomarkers has been published. However, to date there is no non-invasive marker of cellular radiosensitivity identified for clinical routinely use. In this review, the main functional and metabolic imaging isotopic techniques for tumor radiosensitivity that have been explored over the last years are being described. This indirect evaluation fall into 3 topics associated with tumor proliferation rate or apoptosis, tumor hypoxic fraction, neoangiogenesis and the intrinsic radiosensitivity of clonogenic tumor cells. The final objective of the radiosensitivity monitoring during radiotherapy would be to adapt treatment strategy for overcoming the identified radioresistance mechanism such as hypoxia by the addition of radiosensitisers for example. This would allow better tumor control rather than continue inefficient and costly treatment delivery, which in addition could compromise outcome.

[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.