Confrontation des données de la TEP/TDM au 18FDG initiale aux statuts p16 (INK4a) et HPV des cancers des VADS localement avancés traités par radiochimiothérapie

PurposeThe overexpression of p16 and HPV status are now well established as independent prognostic factors in head and neck squamous cell carcinoma (HNSCC). It was suggested that some parameters derived from initial 18F-FDG PET are also independent prognostic factors. Our purpose was to study the correlation between virology and pretreatment PET/CT in locally advanced HNSCC treated by radio-chemotherapy.MethodsForty HNSCC patients with tumor volumes > 3 cm³ were prospectively recruited. All patients underwent initial 18F-FDG PET/CT, from which metabolic volume, intensity (SUV), overall activity, heterogeneity and shape parameters were extracted. The correlation of these parameters with virological data extracted from pre treatment biopsy, including p16 expression, DNA HPV 16 and HPV status (p16 + DNA HPV 16) was subsequently studied.ResultsP16 + tumors exhibited higher SUV_max (P = 0.028) and SUV_mean (P = 0.02). P16+ tumors were also more heterogeneous, albeit with a lower correlation (P = 0.004 for local heterogeneity). In addition, P16+ and HPV+ tumors were characterized by less complex shapes (P = 0.03).ConclusionLocally advanced HNSCC show specific PET characteristics in case of P16+ tumors. The relationship between those different biological characterization approaches and overall patient outcome needs to be investigated.     

Valeur pronostique de la TEP/TDM dans le bilan initial du cancer du col utérin : SUVmax de la tumeur primitive et stadification ganglionnaire

PurposeWe investigated the prognostic significance of F-18 fluorodeoxyglucose (FDG) uptake measured as maximum Standardized Uptake Value (SUV_max) in primary tumor by positron emission tomography/computed tomography (PET/CT) in cervical cancer. The secondary objective was to determine the accuracy of the PET/CT for detecting pelvic lymph node (PLN) and para-aortic lymph node (PALN) metastases.MethodsThis retrospective study included 49 consecutive patients with stage IB1 to IVB cervical cancer. Univariate analysis was performed to determine the relationships between SUV_max value and pathological prognostics factors. Survival was estimated by Kaplan-Meier method. The gold standard of LN metastases was histologic.ResultsA significant difference in SUV_max was observed between stage I and stage II, stage I and stage IV and tumor size ≤ 4 cm and > 4 cm (P = 0.0001). There was a significant correlation between the SUV_max and tumor maximal size (r = 0.597) (P < 0.0001). PLN metastasis was found to be predictive of progression-free survival (P = 0.0007). The negative predictive value (NPV) of the PET/CT for PALN was 100% for locally advanced cervical carcinoma in 24 patients. The specificity and NPV of the PET/CT for PLN in eight early-stage cervical cancer were 100% and 87.5% (7/8) respectively. The PET/CT false-negative PLN measured less than 2 mm.ConclusionOur results demonstrate a correlation between SUV_max and tumor maximal size, which represents an indicator of tumor aggressiveness. PET/CT is effective to predict the absence of PALN in locally advanced cervical carcinoma. PET/CT is not sufficient to predict PLN in early-stage cancer without lymphadenectomy.     

Intérêt pronostique et prédictif de la TEP-TDM au 18F-FDG au bilan initial des mélanomes de stade IIIB-C-D et IV avant traitement par anti-PD-1

PurposeThe advent of immunotherapy by checkpoint inhibitor has profoundly changed the prognosis of patients with metastatic melanoma. The objective of our study was to evaluate the prognostic and predictive performance of 18F-FDG PET/CT of the initial extension assessment of stage IIIB-C-D and IV melanomas.MethodsWe retrospectively included 57 patients who had 18F-FDG PET/CT prior to the introduction of anti-PD-1 immunotherapy. The parameters extracted were SUVmax, SUV peak, MTV and TLG of the lesion with highest uptake (MTV LM, TLG LM), as well as MTV total and TLG total, obtained by adaptive segmentation. The18F-FDG PET/CT were dichotomized using the optimal threshold measured according to the area under the curve in the ROC (Receiver Operation Characteristic) curves. These parameters were evaluated using a Cox model. Overall survival and progression-free survival analyses were performed using the Kaplan Meier model.ResultsThe median follow-up was 25.4 months, 38 patients had progressed or recurred, and 20 patients had died. TLG LM > 132.59 (P = 0.0011), MTV total > 12 cm³ (P = 0.0139), and TLG > 94.17 (P = 0.0084) were significantly associated with a shorter progression-free survival. TLG LM > 145.92 (P = 0.0062), MTV total > 10.16 cm³ (P = 0.0051), and a metastatic spread > 2 organs (P = 0.0001) were associated with a shorter overall survival.ConclusionWe confirm the potential prognostic interest of PET-TDM at 18FDG before immunotherapy of stage IIIB-C-D and IV melanomas on progression-free survival and overall survival. The combination of these metabolic markers reflecting tumor burden with clinical and biological prognostic factors could allow early identification of patients at high risk of anti-PD-1 failure.     

Comparison of 68GA-FAPI-04 PET/CT and 18F-FDG PET/CT in detection of metastatic bone disease in various cancers

ObjectiveOur aim in this retrospective study was to compare the diagnostic accuracy of ⁶⁸Ga-FAPI-04 PET/CT and ¹⁸F-FDG PET/CT in detecting bone metastases of various cancers and to evaluate the potential usefulness of ⁶⁸Ga-FAPI-04 PET/CT in detecting metastatic bone disease.Material and methodOur retrospective study included 44 patients diagnosed with bone metastases due to various cancers between January 2021 and February 2022. All patients underwent ⁶⁸Ga-FAPI-04 PET/CT and ¹⁸F-FDG PET/CT imaging within 14 days. In the semi-quantitative analysis of the skeletal system, all regions with higher uptake than background activity were considered pathological. SUVmax and Metastasis-to-background ratio (TBR) values were calculated from metastatic sites.ResultsA total of 827 bone metastases were detected in our study. The diagnostic accuracies of FAPI PET/CT and ¹⁸F-FDG PET/CT were 91.8% and 81.5%, respectively (P < 0.001). When all bone metastases were compared, the SUVmax of ⁶⁸Ga-FAPI-04 PET/CT was statistically significantly higher than that of ¹⁸F-FDG PET/CT (median 6.15 vs. 5.2; P < 0.001). When FDG and FAPI SUVmax values were compared according to metastasis types, FAPI SUVmax and TBR values in osteolytic, medullary and mixed type bone metastases were found to be statistically significantly higher than FDG (P-values: < 0.001, < 0.001, < 0.001, respectively). There was no statistically significant difference between FDG and FAPI SUVmax values in osteoblastic bone metastases (P = 0.26).ConclusionIt has been shown that ⁶⁸Ga-FAPI-04 PET/CT is superior to ¹⁸F-FDG PET/CT in detecting metastatic bone disease and may have more clinical impact on disease management.     

TEP/TDM 18F-choline dans les récidives biologiques des cancers de la prostate traites par radiothérapie externe ou curiethérapie : impact du PSA et de sa cinétique

AimTo determine the impact of PSA and its kinetics on ¹⁸F-Choline PET/CT (FCH PET) ability to detect site of relapse in prostate cancer initially treated with external beam radiotherapy (EBRT) or brachytherapy (IBT).MethodsWe retrospectively enrolled PET FCH performed for suspicion of biochemical relapse after EBRT/IBT from January 2010 to January 2017 at Institut Curie. PSA_trigger, ΔPSA_nadir (PSA_trigger-PSA_nadir), PSA doubling time (PSA_dt) and velocity (PSA_vel) were compared between positive and negative results. Logistic regression analysis was used to determine the relationship between these parameters and PET ability to detect True Positives (TP).ResultsIn all, 271 FCH PET met the inclusion criteria: 169 after treatment with EBRT and 102 after IBT. Positivity rate was 67.9%, and 63.4% of TP were local relapses. Overall sensitivity and specificity were 81.2% and 71.0%. PSA_trigger was 3.32 ng/mL (interquartile space: IQS 2.28–5.77) when PET was negative and 5.15 ng/mL (IQS 3.16–10.17) when positive, ΔPSAnadir was respectively 2.76 ng/mL (IQS 1.84–4.69) and 4.57 ng/mL (IQS 2.48–8.85), PSA_dt 10.78 months (IQS 5.46–20.07) and 7.23 months (EI 2.58–14.14), and PSA_vel 2.16 ng/mL/year (EI 1.02–4.80) et 4.92 ng/mL/year (1.89–16.02) (P < 0.001). Positivity rate increased with PSA_trigger and ΔPSA_nadir. We found PSA_dt ≤ 9 months (P = 0.029; OR = 2.97, IC_95% [1.12–7.88]) and ΔPSA_nadir ≥ 3 ng/mL (P = 0.03; OR = 2.56, IC_95% [1.37–4.77]) to be independent predictive factors of PET sensitivity.ConclusionDetection of relapse after EBRT or IBT with PET FCH is influenced by PSA and its kinetics. In our study, PSA_dt and ΔPSA_nadir were independant predictors of PET performance, but initial treatment and tumor characteristics were not.     

TEP au 18-FDG et carcinose péritonéale d’origine ovarienne : valeurs diagnostique et pronostique avant chimio-hyperthermie intra-péritonéale (CHIP)

AimEvaluate 18-FDG PET/CT diagnostic and prognostic value before HIPEC.Materials and methodsThis retrospective monocentric study included 38 patients with recurrent (n = 27) or primary (n = 11) ovarian cancer who were blinded reviewed for the presence of peritoneal lesions on PET/CT before HIPEC treatment. The results were compared to surgical and histopathological findings, and to survival curves.ResultsThirty-two patients had peritoneal carcinomatosis based on surgical and histopathological findings, and 19 based on PET. There was no suspicious site of abnormal FGD uptake in the supradiaphragmatic regions. The sensitivity and specificity were respectively 56.2 and 100%. Among the 14 false negative patients, 11 had infracentimetric peritoneal implants, and most of them (n = 13) had chemotherapy before HIPEC. There was significantly more patients treated by chemotherapy in the negative PET group (P = 0.02). Even if the event rate observed was higher in the positive PET group for both event free and overall survival (respectively 68% vs. 64% and 26.3% vs. 17.6%), no significant difference was observed using the survival curves (respectively P = 0.62 and 0.59).ConclusionFDG PET/CT before HIPEC showed excellent specificity and lower sensitivity, due to small peritoneal implants and probably to chemotherapy before HIPEC. No significant prognostic value of FDG PET was observed in our study. FDG PET could be considered as a useful tool for detecting distant metastasis with an impact on therapeutic management.     

Radiosynthesis of N-(4-chloro-3-[11C]methoxyphenyl)-2-picolinamide ([11C]ML128) as a PET radiotracer for metabotropic glutamate receptor subtype 4 (mGlu4)

N-(Chloro-3-methoxyphenyl)-2-picolinamide (3, ML128, VU0361737) is an mGlu₄ positive allosteric modulator (PAM), which is potent and centrally penetrating. 3 is also the first mGlu₄ PAM to show efficacy in a preclinical Parkinson disease model upon systemic dosing. As a noninvasive medical imaging technique and a powerful tool in neurological research, positron emission tomography (PET) offers a possibility to investigate mGlu₄ expression in vivo under physiologic and pathological conditions. We synthesized a carbon-11 labeled ML128 ([¹¹C]3) as a PET radiotracer for mGlu₄, and characterized its biological properties in Sprague Dawley rats. [¹¹C]3 was synthesized from N-(4-chloro-3-hydroxyphenyl)-2-picolinamide (2) using [¹¹C]CH₃I. Total synthesis time was 38 ± 2.2 min (n = 7) from the end of bombardment to the formulation. The radioligand [¹¹C]3 was obtained in 27.7 ± 5.3% (n = 5) decay corrected radiochemical yield based on the radioactivity of [¹¹C]CO₂. The radiochemical purity of [¹¹C]3 was >99%. Specific activity was 188.7 ± 88.8 GBq/mol (n = 4) at the end of synthesis (EOS).PET images were conducted in 20 normal male Sprague Dawley rats including 11 control studies, 6 studies blocking with an mGlu₄ modulator (4) to investigate specificity and 3 studies blocking with an mGlu₅ modulator (MTEP) to investigate selectivity. These studies showed fast accumulation of [¹¹C]3 (peak activity between 1–3 min) in several brain areas including striatum, thalamus, hippocampus, cerebellum, and olfactory bulb following with fast washout. Blocking studies with the mGlu₄ modulator 4 showed 22–28% decrease of [¹¹C]3 accumulation while studies of selectivity showed only minor decrease supporting good selectivity over mGlu₅. Biodistribution studies and blood analyses support fast metabolism. Altogether this is the first PET imaging ligand for mGlu₄, in which the labeled ML128 was used for imaging its in vivo distribution and pharmacokinetics in brain.     

Synthesis and evaluation of copper-64 labeled benzofuran derivatives targeting β-amyloid aggregates

In vivo imaging of β-amyloid (Aβ) aggregates consisting of Aβ(1–40) and Aβ(1–42) peptides by positron emission tomography (PET) contributes to the diagnosis and therapy for Alzheimer’s disease (AD). Because ⁶⁴Cu (t_1/2 = 12.7 h) is a radionuclide for PET with a longer physical half-life than ¹¹C (t_1/2 = 20 min) and ¹⁸F (t_1/2 = 110 min), it is an attractive radionuclide for the development of Aβ imaging probes that are suitable for routine use. In the present study, we designed and synthesized two novel ⁶⁴Cu labeled benzofuran derivatives and evaluated their utility as PET imaging probes for Aβ aggregates. In an in vitro binding assay, 6 and 8 showed binding affinity for Aβ(1–42) aggregates with a K_i value of 33 and 243 nM, respectively. In addition, these probes bound to Aβ plaques deposited in the brain of an AD model mouse in vitro. In a biodistribution experiment using normal mice, these probes showed low brain uptake (0.33% and 0.36% ID/g) at 2 min post-injection. Although refinement to enhance brain uptake is needed, [⁶⁴Cu]6 and [⁶⁴Cu]8 demonstrated the feasibility of developing novel PET probes for imaging Aβ aggregates.     

A 68Ga complex based on benzofuran scaffold for the detection of β-amyloid plaques

Since the imaging of β-amyloid (Aβ) plaques in the brain is believed to be a useful tool for the early diagnosis of Alzheimer’s disease (AD), a number of imaging probes to detect Aβ plaques have been developed. Because the radionuclide ⁶⁸Ga (t_1/2 = 68 min) for PET imaging could become an attractive alternative to ¹¹C and ¹⁸F, we designed and synthesized a benzofuran derivative conjugated with a ⁶⁸Ga complex (⁶⁸Ga-DOTA-C3-BF) as a novel Aβ imaging probe. In an in vitro binding assay, Ga-DOTA-C3-BF showed high affinity for Aβ(1-42) aggregates (K_i = 10.8 nM). The Ga-DOTA-C3-BF clearly stained Aβ plaques in a section of Tg2576 mouse, reflecting the affinity for Aβ(1-42) aggregates in vitro. In a biodistribution study in normal mice, ⁶⁸Ga-DOTA-C3-BF displayed low initial uptake (0.45% ID/g) in the brain at 2 min post-injection. While improvement of the brain uptake of ⁶⁸Ga complexes appears to be essential, these results suggest that novel PET imaging probes that include ⁶⁸Ga as the radionuclide for PET may be feasible.     

Performances de la TEP au 18F-FDG dans la caractérisation initiale de la lésion primitive du cancer du sein

Objective¹⁸F-FDG PET/CT is for the moment not recommended for stage T of the TNM classification of breast cancer. The aim of our study was to evaluate the performance of ¹⁸F-FDG PET/CT in the initial staging of breast tumors. Tumor size, skin involvement and inflammation as well as the relationship between primary tumor maximum standardized uptake value (SUVmax) and histopathological grade (SBR), molecular tumor subtypes (luminal A and B, Her2 enriched, triple negative), estrogen receptors (ER), progesterone receptors (PR) and focality were evaluated.MethodsHistological reports of patients operated for breast cancer, without neoadjuvant chemotherapy, were compared to preoperative ¹⁸F-FDG PET/CT.ResultsSeventy-four patients who underwent surgery in 2016 were included. ¹⁸F-FDG PET/CT was able to visualize primary tumors in 91% and to correctly classify the T stage of the TNM classification in 81% of the cases, to detect multifocality in 73% and cutaneous and inflammatory breast cancers in 100%. The uptake intensity of ¹⁸F-FDG (SUVmax) was significantly correlated with histo-prognostic factors such as SBR grade (P = 0.02), lack of expression of estrogen receptors (ER) (P = 0.01) and progesterone (PR) (P = 0.02), positive HER2 status (P = 0.01) or triple negative subtype tumors (P = 0.02).Conclusion¹⁸F-FDG PET/CT provides relevant elements for local assessment, in particular, tumor focality and inflammatory character in addition to ensuring the regional and extension assessment.     

Synthesis and in vivo evaluation of [18F]2-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)-dione ([18F]FECUMI-101) as an imaging probe for 5-HT1A receptor agonist in nonhuman primates

The 5-HT_1AR partial agonist PET radiotracer, [¹¹C]CUMI-101, has advantages over an antagonist radiotracer as it binds preferentially to the high affinity state of the receptor and thereby provides more functionally meaningful information. The major drawback of C-11 tracers is the lack of cyclotron facility in many health care centers thereby limiting widespread clinical or research use. We identified the fluoroethyl derivative, 2-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)dione (FECUMI-101) (K_i = 0.1 nM; E_max = 77%; EC₅₀ = 0.65 nM) as a partial agonist 5-HT_1AR ligand of the parent ligand CUMI-101. FECUMI-101 is radiolabeled with F-18 by O-fluoroethylation of the corresponding desmethyl analogue (1) with [¹⁸F]fluoroethyltosylate in DMSO in the presence of 1.6 equiv of K₂CO₃ in 45 ± 5% yield (EOS). PET shows [¹⁸F]FECUMI-101 binds specifically to 5-HT_1AR enriched brain regions of baboon. The specificity of [¹⁸F]FECUMI-101 binding to 5-HT_1AR was confirmed by challenge studies with the known 5-HT_1AR ligand WAY100635. These findings indicate that [¹⁸F]FECUMI-101 can be a viable agonist ligand for the in vivo quantification of high affinity 5-HT_1AR with PET.     

Synthesis and evaluation of 1-[2-(4-[11C]methoxyphenyl)phenyl]piperazine for imaging of the serotonin 5-HT7 receptor in the rat brain

1-[2-(4-Methoxyphenyl)phenyl]piperazine (4) is a potent serotonin 5-HT₇ receptor antagonist (K_i = 2.6 nM) with a low binding affinity for the 5-HT_1A receptor (K_i = 476 nM). As a potential positron emission tomography (PET) radiotracer for the 5-HT₇ receptor, [¹¹C]4 was synthesized at high radiochemical yield and specific activity, by O-[¹¹C]methylation of 2′-(piperazin-1-yl)-[1,1′-biphenyl]-4-ol (6) with [¹¹C]methyl iodide. Autoradiography revealed that [¹¹C]4 showed in vitro specific binding with 5-HT₇ in the rat brain regions, such as the thalamus which is a region with high 5-HT₇ expression. Metabolite analysis indicated that intact [¹¹C]4 in the brain exceeded 90% of the radioactive components at 15 min after the radiotracer injection, although two radiolabeled metabolites were found in the rat plasma. The PET study of rats showed moderated uptake of [¹¹C]4 in the brain (1.2 SUV), but no significant regional difference in radioactivity in the brain. Pretreatment with 5-HT₇-selective antagonist SB269970 (3) did not decrease the uptake of [¹¹C]4 in the rat brain. Further studies are warranted that focus on the development of PET ligand candidates with higher binding affinity for 5-HT₇ and higher in vivo stability in brain than 4.     

Synthesis and biological evaluation of 18F-labled 2-phenylindole derivatives as PET imaging probes for β-amyloid plaques

A novel series of fluorinated 2-phenylindole derivatives were synthesized and evaluated as β-amyloid imaging probes for PET. The in vitro inhibition assay demonstrated that their binding affinities for Aβ_1–42 aggregates ranged from 28.4 to 1097.8 nM. One ligand was labeled with ¹⁸F ([¹⁸F]1a) for its high affinity (K_i = 28.4 nM), which was also confirmed by in vitro autoradiography experiments on brain sections of transgenic mouse (C57BL6, APPswe/PSEN1, 11 months old, male). In vivo biodistribution experiments in normal mice showed that this radiotracer displayed high initial uptake (5.82 ± 0.51% ID/g at 2 min) into and moderate washout (2.77 ± 0.31% ID/g at 60 min) from the brain. [¹⁸F]1a could be developed as a promising new PET imaging probe for Aβ plaques although necessary modifications are still needed.     

N-(3,4-Dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[11C]methylphenyl)thiazol-2-yl]-1-carboxamide: A promising positron emission tomography ligand for fatty acid amide hydrolase

To visualize fatty acid amide hydrolase (FAAH) in brain in vivo, we developed a novel positron emission tomography (PET) ligand N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[¹¹C]methylphenyl)thiazol-2-yl]-1-carboxamide ([¹¹C]DFMC, [¹¹C]1). DFMC (1) was shown to have high binding affinity (IC₅₀: 6.1 nM) for FAAH. [¹¹C]1 was synthesized by C–¹¹C coupling reaction of arylboronic ester 2 with [¹¹C]methyl iodide in the presence of Pd catalyst. At the end of synthesis, [¹¹C]1 was obtained with a radiochemical yield of 20 ± 10% (based on [¹¹C]CO₂, decay-corrected, n = 5) and specific activity of 48–166 GBq/μmol. After the injection of [¹¹C]1 in mice, high uptake of radioactivity (>2% ID/g) was distributed in the lung, liver, kidney, and brain, organs with high FAAH expression. PET images of rat brains for [¹¹C]1 revealed high uptakes in the cerebellar nucleus (SUV = 2.4) and frontal cortex (SUV = 2.0), two known brain regions with high FAAH expression. Pretreatment with the FAAH-selective inhibitor URB597 reduced the brain uptake. Higher than 90% of the total radioactivity in the rat brain was irreversible at 30 min after the radioligand injection. The present results indicate that [¹¹C]1 is a promising PET ligand for imaging of FAAH in living brain.     

Synthesis and preclinical characterization of 1-(6′-deoxy-6′-[18F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-6′-[18F]FAZAL) as a positron emission tomography radiotracer to assess tumor hypoxia

Positron emission tomography (PET) using fluorine-18 (¹⁸F)-labeled 2-nitroimidazole radiotracers has proven useful for assessment of tumor oxygenation. However, the passive diffusion-driven cellular uptake of currently available radiotracers results in slow kinetics and low tumor-to-background ratios. With the aim to develop a compound that is actively transported into cells, 1-(6′-deoxy-6′-[¹⁸F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-[¹⁸F]1), a putative nucleoside transporter substrate, was synthetized by nucleophilic [¹⁸F]fluoride substitution of an acetyl protected labeling precursor with a tosylate leaving group (β-6) in a final radiochemical yield of 12 ± 8% (n = 10, based on [¹⁸F]fluoride starting activity) in a total synthesis time of 60 min with a specific activity at end of synthesis of 218 ± 58 GBq/μmol (n = 10). Both radiolabeling precursor β-6 and unlabeled reference compound β-1 were prepared in multistep syntheses starting from 1,2:5,6-di-O-isopropylidene-α-d-allofuranose. In vitro experiments demonstrated an interaction of β-1 with SLC29A1 and SLC28A1/2/3 nucleoside transporter as well as hypoxia specific retention of β-[¹⁸F]1 in tumor cell lines. In biodistribution studies in healthy mice β-[¹⁸F]1 showed homogenous tissue distribution and excellent metabolic stability, which was unaffected by tissue oxygenation. PET studies in tumor bearing mice showed tumor-to-muscle ratios of 2.13 ± 0.22 (n = 4) at 2 h after administration of β-[¹⁸F]1. In ex vivo autoradiography experiments β-[¹⁸F]1 distribution closely matched staining with the hypoxia marker pimonidazole. In conclusion, β-[¹⁸F]1 shows potential as PET hypoxia radiotracer which merits further investigation.     

Quantification and monitoring of PET/CT data in multicentre trials: The Swiss SAKK 56/07 trial experience

AimTo outline the importance of continuous monitoring of quantitative positron emission tomography (PET) data in multicentre trials to minimize quantitative bias in longitudinal intra-patient PET studies in light of the multicentre SAKK 56/07 experience in quantification and monitoring ¹⁸F-FDG PET/CT data.Patients and methodsWe collected 64 uniform phantom ¹⁸F-FDG PET acquisitions periodically at the enrolling centres (12 European institutions). A core-laboratory analysed them for standard uptake value (SUV) accuracy (desired 1.00 ± 10%) and acceptable image noise was defined by a coefficient of variation (COV) less than 15%. In total, 151 patients ¹⁸F-FDG PET acquisitions (baseline and follow-up) were also collected and analysed to verify longitudinal coherence of main acquisition/reconstruction parameters (DICOM tags verification) and patient preparation, in particular the uptake time (desired uptake time [UT] = 60 ± 10 min).ResultsUniform phantom PET acquisition satisfied the inclusion criteria in 58/64 (89%) examinations. All PET scanner exhibited comparable SUV quantification, but we found large dispersion in terms of noise, with COV ranging 3–15%. Only 1 phantom PET acquisition was out of range with COV = 21.5%. Patient data exhibited important variation in uptake time with UT = 65 ± 10 min (mean ± SD), with only 111/151 (74%) patients’ examinations satisfying inclusion criteria while 26% were out of range.ConclusionsRegular monitoring of PET data in multicentre trials is capital to ensure longitudinal intra-patient PET data consistence and minimize quantitative bias while it helps to spread the culture of quality in participating centre. Recent EARL (EANM Research Ltd) standardization and unification of procedures is a welcome step in this direction.     

Comparaison de deux méthodes de mesure des TLG en TEP au 18-FDG dans le mélanome métastatique

IntroductionThere are many automated segmentation softwares in PET-CT, but none of them is used as gold standard. The aim of this study is to compare two segmentation softwares, one based on maximum intensity projection (MIP-based) and the second: PETVCAR^®, to measure TLG in patients with metastatic melanoma treated by vemurafenib.Materials and methodsSixteen patients were assessed by PET using 18-fluorodesoxyglucose (18-FDG) before and during the treatment with vemurafenib. TLG were measured by MIP-based and PETVCAR^® and then analysed in initial PET, all PET, by organ and added for each PET.ResultsThere is a good correlation between TLG in each method (r = 0.96 with P = 0 on 439 lesions on all PET). The mean difference between TLG PETVCAR^® and TLG MIP-based is negative. Segmentations are larger with MIP-based than with PETVCAR^® with discrepancies observed for larger and heterogeneous lesions. SUV_max doesn’t seem to be the factor causing these discrepancies. Correlation between the difference of TLG and their mean is also strong especially in bones, nodes and subcutaneous lesions.ConclusionBoth methods have a good correlation in spite of discrepancies observed for large or heterogeneous lesions. These lesions segmentations are larger with the method based on MIP than with PETVCAR^®.     

Segmentation d’images de lésions cérébrales primitives en TEP FET : influence du volume de travail

Purpose(1) Evaluate the reproducibility of segmentation methods depending on the preselection region for tumour volume determination on ¹⁸F-fluoro-ethyl-tyrosine (FET) PET. (2) Evaluate the intra and inter-operator reproducibility of the manual delineation. (3) Compare this delineation with the segmentation methods.Materials and methodsEighteen FET PET of patients with glioblastoma were analysed. Preselection regions were determined prior to any segmentation. Two physicians delineated the tumour volume manually. The tumour volume was also delineated with a threshold method (40 and 70% of SUV_max), and a random walk based method. Pearson coefficient (r) (P < 0.05 for r > 0.468) and Jaccard indices (JI) were used to compare the volumes.ResultsManual delineation was reproducible with r = 0.97 and IJ = 0.65 for intra-operator, and r = 0.76 and IJ = 0.45 for inter-operator reproducibility. The preselection regions for a given lesion were different and the segmentation varied with the preselection region: r = 0.55 JI = 0.58; r = 0.85 JI = 0.83; r = 0.70 JI = 0.39 respectively for the threshold of 40%, 70% and the random walk. The segmentation differed form de manual delineation with r = 0.37 and JI = 0.16; r = 0.54 and JI = 0.42; r = 0.43 and JI = 0.37 respectively for the threshold of 40%, 70% and the random walk.ConclusionThe reproducibility of the segmentation methods depends extensively on the preselection region. The intra-operator reproducibility of cerebral lesion delineation on FET PET is satisfactory. The inter-operator reproducibility could be improved.     

Découverte fortuite de fixations colorectales focales du FDG en TEP/TDM : corrélation aux données de la coloscopie

PurposeFDG-PET is an established tool for the diagnosis of recurrent or metastatic colorectal carcinoma. Several case series suggest that FDG-PET often detects incidental adenomatous polyps or colorectal adenocarcinomas. The aim of this study was to correlate unexpected colorectal foci of FDG uptake to pathology findings after systematic colonoscopy.Patients and methodsWe reviewed the records of 3541 patients who underwent FDG PET/CT in our institution over a 30-month period for the assessment of a known or suspected malignancy. In 85 of them, incidental, nodular shaped and well-circumscribed foci of abnormal uptake were identified in the area of the colon or rectum. Patients with segmental or diffuse abnormal colorectal uptake were excluded, as well as patients with known benign or malignant colorectal disease. Colonoscopy and complete pathology report was available in 29 patients. Maximal standardized uptake value (SUV_max) was measured in all lesions.ResultsUnexpected colorectal foci of FDG uptake were associated with colonoscopic abnormalities in 23 patients (true positive rate: 79 %). Adenocarcinomas were found in six patients (SUV_max = 7.3 ± 2.6), tubulous adenomas in four patients (SUV_max = 7.3 ± 4.9) and tubulovillous adenomas in 12 patients (SUV_max = 4.2 ± 1.1). Hyperplasic polyps with no sign of dysplasia were found in the last patient (SUV_max = 3.3). Concomitant CT abnormalities were found on PET/CT fusion in eight patients and consisted of wall thickening (n = 5) or nodular mass (n = 3). Conversely, PET was falsely positive in six patients (21 %), with no concomitant CT abnormalities and no abnormal findings at endoscopy (SUV_max = 6.2 ± 2.8, no significant difference with true positive lesions).ConclusionOur findings emphasize the need to perform a colonoscopy in front of incidental nodular colorectal foci of FDG uptake because malignant or pre-malignant neoplasms, which are not clinically apparent, are found in more than three-quarter of cases.     

Intégration des critères métaboliques de la TEP au 18FDG pour le choix des lésions cibles en imagerie onco-hématologique

IntroductionMalignant lymphoma is a heterogeneous and widespread disease. The morphological response assessment is currently based on the choice of target lesions at baseline, defined by size criteria on enhanced CT (eCT). FDG PET/CT is now commonly used at staging and the aim of this study was to evaluate the relevance of using metabolic criteria rather than size criteria to define the target lesions.Patients and methodsFifty-nine patients with aggressive lymphoma were retrospectively included. Target lesions were chosen by two radiologists on eCT and by two nuclear physicians on PET/CT. Response assessment, based on the sum of the products of the greatest diameters of up to six target lesions chosen either by size or metabolic criteria, was computed and compared to a clinical gold standard (GS) for each patient. Interobserver agreement and comparison to the GS were assessed with kappa (κ) and intraclass correlation (ICC) statistics.ResultsThe spatial distribution of target nodal areas was equivalent among eCT and PET/CT readers with a maximum of target lesions in cervical and mediastinal areas. Choosing with PET/CT led to significant heterogeneity in the size of target lesions when compared with eCT alone (P = 0.03). Interobserver agreement for quantifying the response rate was equivalent in both groups. However, there was a greater correlation to the response of the GS when using PET/CT to target the patient (κ = 0.64 vs. 0.47) and an increased rate of complete responses.ConclusionsMetabolic criteria can replace current size criteria to define target lesions on FDG PET/CT. The morphological response rate appears accurate with an increased rate of complete responses after therapy and a better correlation to the haematological standard of reference.