COVID-19 pneumonia: relationship between inflammation assessed by whole-body FDG PET/CT and short-term clinical outcome.

PURPOSE: [18F]-2-Fluoro-2-deoxy-D-glucose PET/CT (FDG PET/CT) is a sensitive and quantitative technic for detecting inflammatory process. Glucose uptake is correlated with an increased anaerobic glycolysis seen in activated inflammatory cells such as monocytes, lymphocytes, and granulocytes. The aim of the study was to assess the inflammatory status at the presumed peak of the inflammatory phase in non-critically ill patients requiring admission for COVID-19. METHODS: Patients admitted with COVID-19 were prospectively enrolled. FDG PET/CT was performed from day 6 to day 14 of the onset of symptoms. Depending on FDG PET/CT findings, patients' profiles were classified as "inflammatory" or "low inflammatory." FDG PET/CT data were compared with chest CT evolution and short-term clinical outcome. All inflammatory sites were reported to screen potential extra-pulmonary tropism. RESULTS: Thirteen patients were included. Maximum standardized uptake values ranged from 4.7 to 16.3 in lungs. All patients demonstrated increased mediastinal lymph nodes glucose uptake. Three patients (23%) presented mild nasopharyngeal, two patients (15%) bone marrow, and five patients (38%) splenic mild increase in glucose uptake. No patient had significant digestive focal or segmental glucose uptake. There was no significant physiological myocardial glucose uptake in all patients except one. There was no correlation between PET lung inflammatory status and chest CT evolution or short-term clinical outcome. CONCLUSION: Inflammatory process at the presumed peak of the inflammatory phase in COVID-19 patients is obvious in FDG PET/CT scans. Glucose uptake is heterogeneous and typically focused on lungs. TRIAL REGISTRATION: NCT04441489. Registered 22 June 2020 (retrospectively registered).

Diagnostic performance and impact on patient management of 68Ga-DOTA-TOC PET/CT for detecting osteomalacia-associated tumours.

PURPOSE: Oncogenic osteomalacia is an endocrine disorder induced by small benign tumours (TIO) producing excessive fibroblast growth factor-23 (FGF23). The only way of curing oncogenic osteomalacia is surgical resection of the culprit TIO, which is extremely difficult to detect using conventional imaging modalities due to its small size and variable location in the body. Since TIO frequently overexpress somatostatin receptors, a clinical utility of SPECT or PET with radiolabelled somatostatin analogues has been reported. Among them, 68Ga-DOTA-TOC has recently been granted a marketing authorization, facilitating its routine application. We report here the results of the first series evaluating the diagnostic performance of 68Ga-DOTA-TOC PET/CT in detecting TIO and its impact on patient management. METHODS: 68Ga-DOTA-TOC PET/CT and clinical and imaging data from 15 patients with clinical and biochemical signs of oncogenic osteomalacia were retrospectively reviewed. The 68Ga-DOTA-TOC PET/CT findings were compared with the results of post-surgical pathology and clinical and biochemical follow-up. RESULTS: 68Ga-DOTA-TOC PET/CT resulted in the detection of one focus suspicious for TIO in nine of 15 patients (60%), and a tumour was surgically removed in eight. Post-operative pathology confirmed a TIO in those eight patients whose symptoms diminished promptly and biochemical anomalies resolved. 68Ga-DOTA-TOC PET/CT sensitivity, specificity and accuracy were 73%, 67% and 71%, respectively. 68Ga-DOTA-TOC PET/CT findings affected patient management in 67% of cases. In particular, 68Ga-DOTA-TOC PET/CT was able to detect the TIO with a negative or a false-positive result of a previous 111In-pentetreotide SPECT/CT in 5/8 patients (63%) or a previous FDG PET/CT in 7/11 patients (64%). No close relationship was found between the positivity of 68Ga-DOTA-TOC PET/CT and the serum level of a biochemical marker. However, a true-positive result of 68Ga-DOTA-TOC PET/CT was obtained in only one patient with a non-elevated serum level of FGF23. CONCLUSION: 68Ga-DOTA-TOC PET/CT is an accurate imaging modality in the detection of TIO; in particular, it is worthwhile after failure of somatostatin receptor SPECT(/CT) or FDG PET/CT.

Vertebral metastases from neuroendocrine tumours: How to avoid false positives on 68Ga-DOTA-TOC PET using CT pattern analysis?

OBJECTIVES: To develop criteria to improve discrimination between vertebral metastases from neuroendocrine tumours (NETs) and benign bone lesions on PET combined with CT using DOTA-D-Phe1-Tyr3-octreotide labelled with gallium-68 (68Ga-DOTA-TOC). METHODS: In 535 NET patients, 68Ga-DOTA-TOC PET/CT examinations were reviewed retrospectively for vertebral CT lesions and/or PET foci. For each vertebral PET abnormality, appearance on CT, biological volume (BV), standardized uptake value (SUVmax) and ratios to those of reference organs were determined. All vertebral abnormalities were characterized as a metastasis, a typical vertebral haemangioma (VH) or other benign lesion. RESULTS: In 79 patients (14.8 %), we found 107 metastases, 34 VHs and 31 other benign lesions in the spine. The optimal cut-off values to differentiate metastases from benign lesions were BV ≥0.72 cm3, SUVmax ≥2, SUVmax ratio to a reference vertebra ≥2.1, to liver ≥0.28 and to spleen ≥0.14. They corresponded to lesion-based 68Ga-DOTA-TOC PET/CT sensitivity of 87 %, 98 %, 97 %, 99 % and 94 %, and specificity of 55 %, 100 %, 90 %, 97 %, 100 %, respectively. CONCLUSIONS: The high sensitivity of 68Ga-DOTA-TOC-PET/CT in detecting NET vertebral metastases was confirmed; this study showed that specificity could be improved by combining CT features and quantifying 68Ga-DOTA-TOC uptake. KEY POINTS: • Bone metastases in neuroendocrine tumours correlate with prognosis. • Benign bone lesions may mimic metastases on 68 Ga-DOTA-TOC PET/CT imaging. • The specific polka-dot CT pattern may be missing in some vertebral haemangiomas. • Lesion atypical for haemangiomas can be better characterized by quantifying 68 Ga-DOTA-TOC uptake.

Liposomes for PET and MR Imaging and for Dual Targeting (Magnetic Field/Glucose Moiety): Synthesis, Properties, and in Vivo Studies.

We describe the potentiality of a new liposomal formulation enabling positron emission tomography (PET) and magnetic resonance MR() imaging. The bimodality is achieved by coupling a 68Ga-based radiotracer on the bilayer of magnetic liposomes. In order to enhance the targeting properties obtained under a permanent magnetic field, a sugar moiety was added in the lipid formulation. Two new phospholipids were synthesized, one with a specific chelator of 68Ga (DSPE-PEG-NODAGA) and one with a glucose moiety (DSPE-PEG-glucose). The liposomes were produced according to a fast and safe process, with a high radiolabeling yield. MR and PET imaging were performed on mice bearing human glioblastoma tumors (U87MG) after iv injection. The accumulation of the liposomes in solid tumor is evidenced by MR imaging and the amount is evaluated in vivo and ex vivo according to PET imaging. An efficient magnetic targeting is achieved with these new magnetic liposomes.

18F-fluorocholine versus 18F-fluorodeoxyglucose for PET/CT imaging in patients with suspected relapsing or progressive multiple myeloma: a pilot study.

PURPOSE: Hybrid positron emission tomography/computed tomography (PET/CT) has now become available, as well as whole-body, low-dose multidetector row computed tomography (MDCT) or magnetic resonance imaging (MRI). The radioactive glucose analogue 18F-fluorodeoxyglucose (FDG) is the most widely used tracer but has a relatively low sensitivity in detecting multiple myeloma (MM). We compared FDG with a more recent metabolic tracer, 18F-fluorocholine (FCH), for the detection of MM lesions at time of disease relapse or progression. METHODS: We analyzed the results of FDG and FCH imaging in 21 MM patients undergoing PET/CT for suspected relapsing or progressive MM. For each patient and each tracer, an on-site reader and a masked reader independently determined the number of intraosseous and extraosseous foci of tracer and the intensity of uptake as measured by their SUVmax and the corresponding target/non-target ratio (T/NT). RESULTS: In the skeleton of 21 patients, no foci were found for two cases, uncountable foci were observed in four patients, including some mismatched FCH/FDG foci. In the 15 patients with countable bone foci, the on-site reader detected 72 FDG foci vs. 127 FCH foci (+76 %), whereas the masked reader detected 69 FDG foci vs. 121 FCH foci (+75 %), both differences being significant. Interobserver agreement on the total number of bone foci was very high, with a kappa coefficient of 0.81 for FDG and 0.89 for FCH. Measurement of uptake in the matched foci that took up both tracers revealed a significantly higher median SUVmax and T/NT for FCH vs. FDG. Almost all unmatched foci were FCH-positive FDG-negative (57/59 = 97 % on-site and 56/60 = 93 % on masked reading); they were more frequently observed than matched foci in the head and neck region. CONCLUSIONS: These findings suggest that PET/CT performed for suspected relapsing or progressive MM would reveal more lesions when using FCH rather than FDG.

Consequence of the introduction of routine FCH PET/CT imaging for patients with prostate cancer: a dual centre survey.

BACKGROUND: Fluorocholine(18F) (FCH) was introduced at the beginning of April 2010 in France, Slovenia and three other EU member states for the localisation of bone metastases of prostate cancer with PET. The aim of the study was to compare the evolution of diagnostic imaging in patients with prostate cancer using a new radiopharmaceutical FCH, observed in France and in Slovenia, and to quantify the consequence of the results of new imaging modality on the detection rate of abnormal metastases and recurrences of prostate cancer. PATIENTS AND METHODS: In two centres (France/Slovenia), a survey of the number of nuclear medicine examinations in patients with prostate cancer was performed, covering 5 quarters of the year since the introduction of FCH. For each examination, the clinical and biological circumstances were recorded, as well as the detection of bone or soft tissue foci. RESULTS: Six hundred and eighty-eight nuclear medicine examinations were performed impatients with prostate cancer. Nuclear medicine examinations were performed for therapy monitoring and follow-up in 23% of cases. The number of FCH PET/CT grew rapidly between the 1(st) and 5(th) period of the observation (+220%), while the number of bone scintigraphies (BS) and fluoride(18F) PET/CTs decreased (-42% and -23% respectively). Fluorodeoxyglucose(18F) (FDG) PET/CT remained limited to few cases of castrate-resistant or metastatic prostate cancer in Paris. The proportion of negative results was significantly lower with FCH PET/CT (14%) than with BS (49%) or fluoride(18F) PET/CT (54%). For bone metastases, the detection rate was similar, but FCH PET/CT was performed on average at lower prostate-specific antigen (PSA) levels and was less frequently doubtful (4% vs. 28% for BS). FCH PET/CT also showed foci in prostatic bed (53% of cases) or in soft tissue (35% of cases). CONCLUSIONS: A rapid development of FCH PET/CT was observed in both centres and led to a higher detection rate of prostate cancer lesions.

Incidental uptake of (18)F-fluorocholine (FCH) in the head or in the neck of patients with prostate cancer.

BACKGROUND: Positron emission tomography-computed tomography (PET/CT) with (18)F-fluorocholine (FCH) is routinely performed in patients with prostate cancer. In this clinical context, foci of FCH uptake in the head or in the neck were considered as incidentalomas, except for those suggestive of multiple bone metastases. RESULTS: In 8 patients the incidental focus corresponded to a benign tumour. The standard of truth was histology in two cases, correlative imaging with MRI in four cases, (99m)Tc-SestaMIBI scintigraphy, ultrasonography and biochemistry in one case and biochemistry including PTH assay in one case. The final diagnosis of benign tumours consisted in 3 pituitary adenomas, 2 meningiomas, 2 hyperfunctioning parathyroid glands and 1 thyroid adenoma. Malignancy was proven histologically in 2 other patients: 1 papillary carcinoma of the thyroid and 1 cerebellar metastasis. CONCLUSIONS: To the best of our knowledge, FCH uptake by pituitary adenomas or hyperfunctioning parathyroid glands has never been described previously. We thus discuss whether there might be a future indication for FCH PET/CT when one such tumour is already known or suspected: to detect a residual or recurrent pituitary adenoma after surgery, to guide surgery or radiotherapy of a meningioma or to localise a hyperfunctioning parathyroid gland. In these potential indications, comparative studies with reference PET tracers or with (99m)Tc-sestaMIBI in case of hyperparathyroidism could be undertaken.

18F-fluorodihydroxyphenylalanine vs other radiopharmaceuticals for imaging neuroendocrine tumours according to their type.

6-Fluoro-((18)F)-L-3,4-dihydroxyphenylalanine (FDOPA) is an amino acid analogue for positron emission tomography (PET) imaging which has been registered since 2006 in several European Union (EU) countries and by several pharmaceutical firms. Neuroendocrine tumour (NET) imaging is part of its registered indications. NET functional imaging is a very competitive niche, competitors of FDOPA being two well-established radiopharmaceuticals for scintigraphy, (123)I-metaiodobenzylguanidine (MIBG) and (111)In-pentetreotide, and even more radiopharmaceuticals for PET, including fluorodeoxyglucose (FDG) and somatostatin analogues. Nevertheless, there is no universal single photon emission computed tomography (SPECT) or PET tracer for NET imaging, at least for the moment. FDOPA, as the other PET tracers, is superior in diagnostic performance in a limited number of precise NET types which are currently medullary thyroid cancer, catecholamine-producing tumours with a low aggressiveness and well-differentiated carcinoid tumours of the midgut, and in cases of congenital hyperinsulinism. This article reports on diagnostic performance and impact on management of FDOPA according to the NET type, emphasising the results of comparative studies with other radiopharmaceuticals. By pooling the results of the published studies with a defined standard of truth, patient-based sensitivity to detect recurrent medullary thyroid cancer was 70 % [95 % confidence interval (CI) 62.1-77.6] for FDOPA vs 44 % (95 % CI 35-53.4) for FDG; patient-based sensitivity to detect phaeochromocytoma/paraganglioma was 94 % (95 % CI 91.4-97.1) for FDOPA vs 69 % (95 % CI 60.2-77.1) for (123)I-MIBG; and patient-based sensitivity to detect midgut NET was 89 % (95 % CI 80.3-95.3) for FDOPA vs 80 % (95 % CI 69.2-88.4) for somatostatin receptor scintigraphy with a larger gap in lesion-based sensitivity (97 vs 49 %). Previously unpublished FDOPA results from our team are reported in some rare NET, such as small cell prostate cancer, or in emerging indications, such as metastatic NET of unknown primary (CUP-NET) or adrenocorticotropic hormone (ACTH) ectopic production. An evidence-based strategy in NET functional imaging is as yet affected by a low number of comparative studies. Then the suggested diagnostic trees, being a consequence of the analysis of present data, could be modified, for some indications, by a wider experience mainly involving face-to-face studies comparing FDOPA and (68)Ga-labelled peptides.

Quantitative analysis of 99mTc-pertechnetate thyroid uptake with a large-field CZT gamma camera: feasibility and comparison between SPECT/CT and planar acquisitions.

PURPOSE: The main objective of this study was to evaluate the ability of a large field Cadmium Zinc Telluride (CZT) camera to estimate thyroid uptake (TU) on single photon emission computed tomography (SPECT) images with and without attenuation correction (Tomo-AC and Tomo-NoAC) compared with Planar acquisition in a series of 23 consecutive patients. The secondary objective was to determine radiation doses for the tracer administration and for the additional Computed Tomography (CT) scan. METHODS: Cross-calibration factors were determined using a thyroid phantom, for Planar, Tomo-AC and Tomo-NoAC images. Then Planar and SPECT/CT acquisitions centered on the thyroid were performed on 5 anthropomorphic phantoms with activity ranging from 0.4 to 10 MBq, and 23 patients after administration of 79.2 ± 3.7 MBq of [99mTc]-pertechnetate. We estimated the absolute thyroid activity (AThA) for the anthropomorphic phantoms and the TU for the patients. Radiation dose was also determined using International Commission on Radiological Protection (ICRP) reports and VirtualDoseTMCT software. RESULTS: Cross-calibration factors were 66.2 ± 4.9, 60.7 ± 0.7 and 26.5 ± 0.3 counts/(MBq s), respectively, for Planar, Tomo-AC and Tomo-NoAC images. Theoretical and estimated AThA for Planar, Tomo-AC and Tomo-NoAC images were statistically highly correlated (r < 0.99; P < 10-4) and the average of the relative percentage difference between theoretical and estimated AThA were (8.6 ± 17.8), (- 1.3 ± 5.2) and (12.8 ± 5.7) %, respectively. Comparisons between TU based on different pairs of images (Planar vs Tomo-AC, Planar vs Tomo-NoAC and Tomo-AC vs Tomo-NoAC) showed statistically significant correlation (r = 0.972, 0.961 and 0.935, respectively; P < 10-3). Effective and thyroid absorbed doses were, respectively (0.34CT + 0.95NM) mSv, and (3.88CT + 1.74NM) mGy. CONCLUSION: AThA estimation using Planar and SPECT/CT acquisitions on a new generation of CZT large-field cameras is feasible. In addition, TU on SPECT/CT was as accurate as conventional planar acquisition, but the CT induced additional thyroid exposure. Trial registration Name of the registry: Thyroid Uptake Quantification on a New Generation of Gamma Camera (QUANTHYC). TRIAL NUMBER: NCT05049551. Registered September 20, 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT05049551?cntry=MC&draw=2&rank=4 .

Microvascular injuries, secondary edema, and inconsistencies in lung vascularization between affected and nonaffected pulmonary segments of non-critically ill hospitalized COVID-19 patients presenting with clinical deterioration.

PURPOSE: We aimed to better understand the pathophysiology of SARS-CoV-2 pneumonia in non-critically ill hospitalized patients secondarily presenting with clinical deterioration and increase in oxygen requirement without any identified worsening factors. METHODS: We consecutively enrolled patients without clinical or biological evidence for superinfection, without left ventricular dysfunction and for whom a pulmonary embolism was discarded by computed tomography (CT) pulmonary angiography. We investigated lung ventilation and perfusion (LVP) by LVP scintigraphy, and, 24 h later, left and right ventricular function by Tc-99m-labeled albumin-gated blood-pool scintigraphy with late (60 mn) tomographic albumin images on the lungs to evaluate lung albumin retention that could indicate microvascular injuries with secondary edema. RESULTS: We included 20 patients with confirmed SARS-CoV-2 pneumonia. All had CT evidence of organizing pneumonia and normal left ventricular ejection fraction. No patient demonstrated preserved ventilation with perfusion defect (mismatch), which may discard a distal lung thrombosis. Patterns of ventilation and perfusion were heterogeneous in seven patients (35%) with healthy lung segments presenting a relative paradoxical hypoperfusion and hypoventilation compared with segments with organizing pneumonia presenting a relative enhancement in perfusion and preserved ventilation. Lung albumin retention in area of organizing pneumonia was observed in 12 patients (60%), indicating microvascular injuries, increase in vessel permeability, and secondary edema. CONCLUSION: In hospitalized non-critically ill patients without evidence of superinfection, pulmonary embolism, or cardiac dysfunction, various types of damage may contribute to clinical deterioration including microvascular injuries and secondary edema, inconsistencies in lung segments vascularization suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others. SUMMARY STATEMENT: Microvascular injuries and dysregulation of the balance in perfusion between segments affected by COVID-19 and others are present in non-critically ill patients without other known aggravating factors. KEY RESULTS: In non-critically ill patients without evidence of superinfection, pulmonary embolism, macroscopic distal thrombosis or cardiac dysfunction, various types of damage may contribute to clinical deterioration including 1/ microvascular injuries and secondary edema, 2/ inconsistencies in lung segments vascularization with hypervascularization of consolidated segments contrasting with hypoperfusion of not affected segments, suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others.

An Intravenous 100-mL Lipid Emulsion Infusion Dramatically Improves Myocardial Glucose Metabolism Extinction in Cardiac FDG PET Clinical Practice.

PURPOSE: Physiological myocardial accumulation of FDG impairs the diagnosis of inflammatory/infectious or tumoral myocardial detection by FDG PET/CT. We prospectively evaluated the addition, 3 hours before imaging, of an intravenous 100-mL lipid emulsion infusion (Intralipid) to a high-fat, low-carbohydrate diet (HFLCD) for at least 2 meals followed by a fast of at least 6 to 12 hours in patients referred for the diagnosis of myocardial inflammation, endocarditis, cardiac or paracardiac masses, intracardiac device, or prosthetic valve infections. METHODS: Data of 58 patients consecutively included (28 Intralipid patients, 30 controls with HFLCD alone) were compared. FDG uptake in normal myocardium was scored from 0 (complete myocardial suppression) to 3 (high diffuse uptake). Myocardial maximal, peak, and mean SUV and the rate of interpretable images according to the clinical indication were measured. RESULTS: Compared with controls, Intralipid infusion significantly improved the rate of score 0 (89% vs 63%, P = 0.021), of interpretable images according to the clinical indication (100% vs 72%, P = 0.0047) and decreased all myocardial SUV values (eg, SUVmax median, 1.9 [interquartile range, 1.7-2.5] vs 3.1 [interquartile range, 2.3-4.1]; P < 0.001). CONCLUSIONS: A lipid emulsion infusion in addition to HFLCD better suppresses cardiac glucose metabolism than HFLCD alone.

In vivo monitoring of the therapeutic efficacy of a CXCR1/2 inhibitor with 18F-FDG PET/CT imaging in experimental head and neck carcinoma: A feasibility study.

The chemokine receptors CXCR1/2 play a key role in the aggressiveness of several types of cancers including head and neck squamous cell carcinomas (HNSCCs). In HNSCCs, CXCR1/2 signaling promotes cell proliferation and angiogenesis leading to tumor growth and metastasis. The competitive inhibitor of CXCR1/2, C29, inhibits the growth of experimental HNSCCs in mice. However, a non-invasive tool to monitor treatment response is essential to implement the use of C29 in clinical practices. 18F-FDG PET/CT is a gold-standard tool for the staging and the post-therapy follow-up of HNSCCs patients. Our study aimed to perform the first in vivo monitoring of C29 efficacy by non-invasive 18F-FDG PET/CT imaging. Mice bearing experimental HNSCCs (CAL33) were injected with 18F-FDG (T0) and thereafter treated (n = 7 mice, 9 tumors, 50 mg/kg by gavage) or not (n = 7 mice, 10 tumors) with C29 for 4 consecutive days. Final 18F-FDG-tumor uptake was determined at day 4 (TF). The average relative change (TF-T0) in 18F-FDG tumor uptake was +25.85 ± 10.93 % in the control group vs -5.72 ± 10.07 % in the C29-treated group (p < 0.01). These results were consistent with the decrease of the tumor burden and with the decrease of tumor proliferating Ki67+ cells. These results paved the way for the use of 18F-FDG to monitor tumor response following C29 treatment.

68Ga-DOTATOC PET/CT in detecting neuroendocrine tumours responsible for initial or recurrent paraneoplastic Cushing's syndrome.

PURPOSE: Paraneoplastic Cushing's syndrome (PCS) is frequently caused by neuroendocrine tumours (NETs). Approximately 20% of tumours are still occult years later. Gallium-68 somatostatin receptor-PET/CT is promising for the detection of the causal primary NET, but its role in case of recurrent PCS is rarely reported. We report our experience with DOTATOC PET/CT in localising the causal NET in cases of initial but also recurrent PCS, and its clinical impact. METHODS: A retrospective review of all DOTATOC PET/CTs performed in consecutive patients referred for PCS to our centre, between January 2011 and June 2017, was done. Nineteen patients underwent 26 PET/CTs, 13 for detection of a primary NET, seven for persistent or recurrent PCS after resection, and six for surveillance after resection of NETs previously detected on a DOTATOC PET/CT in our centre. RESULTS: Among the 13 PET/CTs performed to search for primary NET, five were positive: four carcinoid lung tumours were confirmed after resection and one lung focus was not confirmed since surgery would have carried a high risk. Clinical impact was 23% (3/13). Among the seven PET/CTs performed for persistent or recurrent PCS, six were true-positive, with confirmation of metastatic lymph nodes after resection. Clinical impact was 57% (4/7). All PET/CTs performed for surveillance were true-negative. CONCLUSIONS: DOTATOC PET/CT seems to be a valuable tool for detection of the NET responsible for persistent or recurrent PCS after surgery. In this context, DOTATOC PET/CT was more effective than for the detection of the causal tumour in initial PCS.

Early evaluation of the effects of chemotherapy with longitudinal FDG small-animal PET in human testicular cancer xenografts: early flare response does not reflect refractory disease.

AIM: We aimed to evaluate the usefulness of FDG PET in the early prediction of the effects of chemotherapy on human testicular cancer xenografts. MATERIAL AND METHODS: Nude rats bearing subcutaneous human embryonal carcinoma xenografts received either cisplatin (5 mg/kg) or saline serum. Small-animal PET studies were performed on days 0, 2, 4 and 7 and compared to immunochemistry studies, flow cytometry studies and hexokinase assays. RESULTS: Cisplatin treatment resulted in biphasic FDG uptake evolution: a peak was observed on day 2, followed by a marked decrease on day 7 despite an insignificant change in tumour volume. Similarly, a peak in cyclin A immunostaining was observed on days 2 and 4), followed by a significant decrease on day 7. Flow cytometry showed that the cyclin A peak was not related to increased cell proliferation but was due to a transient S and G(2)/M cell cycle arrest. A marked increase in cell apoptosis was observed from day 2 to day 7. GLUT-1 showed a significant decrease on day 7. Macrophagic infiltrate remained stable except for an increase observed on day 7. In control tumours, continuous growth was observed, all immunostaining markers remaining stable over time. Hexokinase activity was significantly lower on day 7 in treated tumours than in controls. CONCLUSION: FDG PET may be useful in the early evaluation of treatment in patients with testicular cancer. In our model, a very early increased [(18)F]-FDG uptake was related to a transient cell cycle arrest and early stage apoptosis but did not reveal refractory disease.

[68Ga]RGD Versus [18F]FDG PET Imaging in Monitoring Treatment Response of a Mouse Model of Human Glioblastoma Tumor with Bevacizumab and/or Temozolomide.

PURPOSE: The aim of this study was to evaluate positron emission tomography (PET) imaging with [68Ga]NODAGA-c(RGDfK) ([68Ga]RGD), in comparison with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), for early monitoring of the efficacy of an antiangiogenic agent associated or not with chemotherapy, in a mouse model of glioblastoma (GB). PROCEDURES: Mice bearing U87MG human GB cells line were parted into five groups of five mice each. One group was imaged at baseline before the treatment phase; another group was treated with bevacizumab (BVZ), another group with temozolomide (TMZ), another group with both agents, and the last one was the control group. Tumors growth and biological properties were evaluated by caliper measurements and PET imaging at three time points (baseline, during treatment t1 = 4-6 days and t2 = 10-12 days). At the end of the study, tumors were counted and analyzed by immunohistochemistry (CD31 to evaluate microvessel density). RESULTS: The tumor volume assessed by caliper measurements was significantly greater at t1 in the control group than in the TMZ + BVZ-treated group or in the BVZ-treated group. At t2, tumor volume of all treated groups was significantly smaller than that of the control group. [18F]FDG PET failed to reflect this efficacy of treatment. In contrast, at t1, the [68Ga]RGD tumor uptake was concordant with tumor growth in controls and in treated groups. At t2, a significant increase in tumor uptake of [68Ga]RGD vs. t1 was only observed in the TMZ-treated group, reflecting a lack of angiogenesis inhibition, whereas TMZ + BVZ resulted in a dramatic tumor arrest, reduction in microvessel density and stable tumor [68Ga]RGD uptake. CONCLUSIONS: [68Ga]RGD is a useful PET agent for in vivo angiogenesis imaging and can be useful for monitoring antiangiogenic treatment associated or not with chemotherapy.

18F-fluorocholine PET/CT in patients with occult biochemical recurrence of prostate cancer: Detection rate, impact on management and adequacy of impact. A prospective multicentre study.

AIM: To prospectively evaluate the clinical impact and the diagnostic performance of FCH-PET/CT in patients with occult biochemical recurrence of prostate cancer (PCa). MATERIALS AND METHODS: Results of 179 patients (mean PSA = 7.5ng/mL) with negative/inconclusive results of pelvic-MRI and of bone-scintigraphy were analysed. To determine the impact of FCH-PET/CT on diagnostic thinking and on patient management, the referring physicians prospectively filled-in a 1st and 2nd questionnaire related to patient's planned management before and after FCH-PET/CT. Based on data from a 6-month follow-up after FCH-PET/CT, an independent assessor blinded to results of FCH-PET/CT determined the adequacy of management changes motivated by FCH-PET/CT. RESULTS: FCH-PET/CT localised foci evocative of recurrent PCa in 59% (105/179) of patients. Results of FCH-PET/CT motivated a change in scheduled patient management in 56% (100/179) of patients; which was considered as adequate in 89% (89/100) of patients. FCH-PET/CT also led to the detection of lung cancer in two patients. CONCLUSION: FCH PET/CT is a powerful tool to localise the sites of occult biochemical recurrence of PCa, leading to an adequate management change in half of patients.

Comparison and evaluation of two RGD peptides labelled with 68Ga or 18F for PET imaging of angiogenesis in animal models of human glioblastoma or lung carcinoma.

The aim of this study was to evaluate two RGD radiotracers radiolabelled with fluorine-18 or gallium-68, in detecting angiogenesis in grafted human tumours and monitoring their treatment with the anti-angiogenic agent bevacizumab. Sixteen mice bearing an U87MG tumour in one flank and a contralateral A549 tumour were treated with intravenous injections of bevacizumab twice a week for 3 weeks. PET images with 18F-RGD-K5 and 68Ga-RGD were acquired before treatment (baseline), after three bevacizumab injections (t1) and after seven bevacizumab injections (t2). In A549 tumours, the treatment stopped the tumour growth, with a tumour volume measured by calliper remaining between 0.28 and 0.40 cm3. The decrease in tumour uptake of both RGD tracers was non-significant. Therefore it was not possible to predict this efficacy on tumour growth based on RGD PET results, whereas ex vivo measurements showed a significantly lower tumour uptake of both tracers in mice sacrificed at t2 vs. at baseline. In U87MG tumours, the uptake measured on PET decreased during treatment, reflecting the partial therapeutic effect observed on tumour volume, consisting in a decrease in the slope of tumour growth. Using 18F-RGD-K5, this decrease in tumour SUVmax became significant at t1, whereas it was also observed with the 68Ga-RGD tracer, but only at t2. 18F-RGD-K5 appeared more efficient than 68Ga-RGD in the visualisation and follow-up of U87MG tumours. The comparison of those results with those of immunohistochemistry at baseline and at t2 favoured the hypothesis that tumour RGD uptake reflects other cancer properties than just its angiogenic capacity.

Improvement of semi-quantitative small-animal PET data with recovery coefficients: a phantom and rat study.

AIM: To evaluate the accuracy of semi-quantitative small-animal PET data, uncorrected for attenuation, and then of the same semi-quantitative data corrected by means of recovery coefficients (RCs) based on phantom studies. MATERIALS AND METHODS: A phantom containing six fillable spheres (diameter range: 4.4-14 mm) was filled with an 18F-FDG solution (spheres/background activity=10.1, 5.1 and 2.5). RCs, defined as measured activity/expected activity, were calculated. Nude rats harbouring tumours (n=50) were imaged after injection of 18F-FDG and sacrificed. The standardized uptake value (SUV) in tumours was determined with small-animal PET and compared to ex-vivo counting (ex-vivo SUV). Small-animal PET SUVs were corrected with RCs based on the greatest tumour diameter. Tumour proliferation was assessed with cyclin A immunostaining and correlated to the SUV. RESULTS: RCs ranged from 0.33 for the smallest sphere to 0.72 for the largest. A sigmoidal correlation was found between RCs and sphere diameters (r(2)=0.99). Small-animal PET SUVs were well correlated with ex-vivo SUVs (y=0.48x-0.2; r(2)=0.71) and the use of RCs based on the greatest tumour diameter significantly improved regression (y=0.84x-0.81; r(2)=0.77), except for tumours with important necrosis. Similar results were obtained without sacrificing animals, by using PET images to estimate tumour dimensions. RC-based corrections improved correlation between small-animal PET SUVs and tumour proliferation (uncorrected data: Rho=0.79; corrected data: Rho=0.83). CONCLUSION: Recovery correction significantly improves both accuracy of small-animal PET semi-quantitative data in rat studies and their correlation with tumour proliferation, except for largely necrotic tumours.

Equivalent Dose Rate 1 Meter from Neuroendocrine Tumor Patients Exiting the Nuclear Medicine Department After Undergoing Imaging.

123I-metaiodobenzylguanidine (MIBG) and 111In-pentetrotide SPECT have been used for functional imaging of neuroendocrine tumors (NETs) for the last 2 decades. More recently, PET/CT imaging with 18F-FDG, 18F-fluorodihydroxyphenylalanine (FDOPA), and 68Ga somatostatin-receptor ligands in NETs has been expanding. A literature search could find no direct measurements of the dose rate from NET patients exiting the nuclear medicine department after undergoing PET/CT with 18F-FDOPA or 68Ga-DOTATOC, a somatostatin analog. Methods: We measured the dose rates from 93 NET patients on leaving the department after undergoing PET/CT or SPECT/CT in our centers. In total, 103 paired measurements of equivalent dose rate at 1 m (EDR-1m) from the sternum and urinary bladder were obtained. The detector faced the sternum or bladder and was 1 m away from and directly in front of the patient. The practice for exiting the department differed according to whether the patient had been referred for PET/CT or for SPECT/CT. PET/CT patients were discharged after imaging, whereas SPECT/CT patients left the department earlier, just after radiopharmaceutical injection. Results: The median administered activity was 122 MBq in 53 68Ga-DOTATOC PET/CT studies, 198 MBq in 15 18F-FDOPA PET/CT studies, and 176 MBq in 13 18F-FDG PET/CT studies. The corresponding median EDR-1m was 4.8, 9.5, and 8.8 µSv/h, respectively, facing the sternum, and 5.1, 10.1, and 9.5 µSv/h, respectively, facing the bladder. The median administered activity was 170 MBq in 12 111In-pentetreotide SPECT/CT studies and 186 MBq in 10 123I-MIBG SPECT/CT studies. The corresponding median EDR-1m was 9.4, and 4.9 µSv/h, respectively, at the level of the sternum, and 9.3 and 4.7 µSv/h, respectively, at the level of the bladder. The EDR-1m was less than 20 µSv/h in all patients. Thus, when exiting the nuclear medicine department, the NET patients injected with 68Ga-DOTATOC or 123I MIBG emitted an average EDR-1m roughly half that of patients injected with other radiopharmaceuticals. This finding is a complementary argument for replacing SPECT by PET somatostatin-receptor imaging. Conclusion: Our current practice of allowing patients to exit after PET/CT imaging or just after SPECT radiopharmaceutical injection appears to be safe from a radiation protection point of view. Restrictive advice is unnecessary for NET patients being discharged from the department.

[Basics of PET and PET/CT imaging: instrumentation and radiopharmaceuticals for clinical diagnosis]. / Bases de la TEP et de la TEP/TDM: machines et médicaments radiopharmaceutiques pour le diagnostic clinique.

Positron emission tomography (PET), like scintigraphy, is a type of functional and molecular imaging. Image resolution is better than with scintigraphy, and tomographic slices are obtained, as with CT and MRI. Modern PET machines are coupled with CT (PET/CT) and yield fused images that combine metabolic and anatomic approaches. Fludeoxyglucose (FDG), a radiolabeled glucose analog, is the most widely used radiopharmaceutical for clinical PET, but several other molecules are proposed for routine use. Clinical trials will determine which are of clinical interest. FDG imaging necessarily involves PET but clinical PET is not only FDG imaging.