Abstract
With the emergence of disease modifying osteoarthritis drugs (DMOAD), imaging methods to quantitatively demonstrate their efficacy and to monitor osteoarthritis progression at the functional ...level are urgently needed. Our group showed that articular cartilage can be quantitatively assessed in nuclear medicine imaging by our radiotracer
99m
Tc-NTP 15-5 targeting cartilage proteoglycans. In this work, surgically induced DMM mice were treated with sprifermin or saline. We investigated cartilage remodelling in the mice knees by
99m
Tc-NTP 15-5 SPECT-CT imaging over 24 weeks after surgery, as wells as proteoglycan biochemical assays. OA alterations were scored by histology according to OARSI guidelines. A specific accumulation of
99m
Tc-NTP 15-5 in cartilage joints was evidenced in vivo by SPECT-CT imaging as early as 30 min post-iv injection. In DMM,
99m
Tc-NTP 15-5 accumulation in cartilage within the operated joints, relative to contralateral ones, was observed to initially increase then decrease as pathology progressed. Under sprifermin,
99m
Tc-NTP 15-5 uptake in pathological knees was significantly increased compared to controls, at 7-, 12- and 24-weeks, and consistent with proteoglycan increase measured 5 weeks post-surgery, as a sign of cartilage matrix remodelling. Our work highlights the potential of
99m
Tc-NTP 15-5 as an imaging-based companion to monitor cartilage remodelling in OA and DMOAD response.
Differentiated thyroid cancer (DTC) is the most common of endocrine cancers. Many studies have focused on recurrence-free survival of DTC patients, however, few studies have addressed overall ...survival rates. Given its very good prognosis, estimating overall or long-term survival in patients with DTC seems rational. So far, neither the impact of pre- and post-ablation thyroglobulin, nor that of initial American Thyroid Association (ATA) risk stratification on long-term disease-specific survival, have been sufficiently studied.
The aim of this study was to determine the factors that influence long-term disease-specific survival and thyroglobulin levels in patients with DTC who have been previously treated with thyroidectomy and radioactive iodine (RAI) remnant ablation.
This observational retrospective study included 1093 patients who were treated for DTC between 1995 and 2010 and are still monitored in our tertiary center. Only patients who needed RAI ablation after thyroidectomy were included in this study. Patients who were treated with RAI following rhTSH stimulation, patients who presented positive anti-thyroglobulin antibodies, and patients who had micro-cancers were excluded. Pre-ablation stimulated thyroglobulin (Pre-ablation sTg) was measured after thyroid hormone withdrawal (THW), just before RAI.
According to ATA standards, 29 patients (2.7%) were classified as high-risk patients. Initial ATA high-recurrence risk rating (HR 21.9; 95% CI: 8.5-56.3), age>55 years (HR 23.8; 95%-CI: 7.5-75.3) and pre-ablation sTg≥30 μg/l (HR 8.4; 95% CI: 4.6-15.3) significantly impacted ten-year survival. Moreover, age over 45 years, ATA moderate-risk and follicular DTC were also significant. Ten-year survival was lower in ATA high-risk patients (51% vs 95% and 93% for the low and intermediate risk; p<10-7), patients older than 55 years (82% vs 98%; p<10-7), and in patients with pre-ablation sTg≥30 (78% vs 95%; p<10-7). Three rates of long-term survival were distinguished: excellent (survival rate of 99% in patients<55 years with pre-ablation sTg <30μg/l) representing 59% of the cohort, moderate (survival rate of 94.5% in patients <55 years with pre-ablation sTg ≥30μg/l or ≥55 years with pre-ablation sTg <30 μg/l) representing 38% of the cohort, and low (survival rate of 49% in patients ≥55 years with pre-ablation sTg ≥30μg/l) representing 3% of the cohort.
Initial ATA high-risk classification, age over 55 years old and pre-ablation sTg ≥30 μg/l are the main negative factors that influence the ten-year survival in DTC. We suggest three categories of overall survival rates. Patients older than 55 years with pre-ablation sTg ≥30 μg/l have the worst survival rate.
Benzamide-based radioligands targeting melanin were first developed for imaging melanoma and then for therapeutic purpose with targeted radionuclide therapy (TRT).
IICF01012 presents a highly ...favorable pharmacokinetics profile in vivo for therapy. Tumour growth reduction and increase survival have been established in preclinical models of melanoma. According the these preclinical results, we initiate a first-in-human study aimed to determine the recommended dose of
IICF01012 to administer for the treatment of patients with pigmented metastatic melanoma.
The MELRIV-1 trial is an open-label, multicentric, dose-escalation phase I trial. The study is divided in 2 steps, a selection part with an IV injection of low activity of
IICF01012 (185 MBq at D0) to select patients who might benefit from
IICF01012 TRT in therapeutic part, i.e. patient presenting at least one tumour lesion with
IICF01012 uptake and an acceptable personalized dosimetry to critical organs (liver, kidney, lung and retina). According to dose escalation scheme driven by a Continual Reassessment Method (CRM) design, a single therapeutic injection of 800 MBq/m
, or 1600 MBq/m
, or 2700 MBq/m
or 4000 MBq/m
of
IICF01012 will be administered at D11 (± 4 days). The primary endpoint is the recommended therapeutic dose of
IICF01012, with DLT defined as any grade 3-4 NCI-CT toxicity during the 6 weeks following therapeutic dose. Safety, pharmacokinetic, biodistribution (using planar whole body and SPECT-CT acquisitions), sensitivity / specificity of
IICF01012, and therapeutic efficacy will be assessed as secondary objectives. Patients who received therapeutic injection will be followed until 3 months after TRT. Since 6 to 18 patients are needed for the therapeutic part, up to 36 patients will be enrolled in the selection part.
This study is a first-in-human trial evaluating the
IICF01012 TRT in metastatic malignant melanomas with a diagnostic dose of the
IICF01012 to select the patients who may benefit from a therapeutic dose of
IICF01012, with at least one tumor lesion with
IICF01012 uptake and an acceptable AD to healthy organ.
Clinicaltrials.gov : NCT03784625 . Registered on December 24, 2018. Identifier in French National Agency for the Safety of Medicines and Health Products (ANSM): N°EudraCT 2016-002444-17.
One of the current challenges in oncology is to develop imaging tools to early detect the response to conventional chemotherapy and adjust treatment strategies when necessary. Several studies ...evaluating PET imaging with 2-deoxy-2-
Ffluoro-D-glucose (
FFDG) as a predictive tool of therapeutic response highlighted its insufficient specificity and sensitivity. The
FFDG uptake reflects only tumor metabolic activity and not treatment-induced cell death, which seems to be relevant for therapeutic evaluation. Therefore, to evaluate this parameter
, several cell death radiotracers have been developed in the last years. However, few of them have reached the clinical trials. This systematic review focuses on the use of
FML-10 (2-(5-
Ffluoropentyl)-2-methylmalonic acid) as radiotracer of apoptosis and especially as a measure of tumor response to treatment. A comprehensive literature review concerning the preclinical and clinical investigations conducted with
FML-10 was performed. The abilities and applications of this radiotracer as well as its clinical relevance and limitations were discussed. Most studies highlighted a good ability of the radiotracer to target apoptotic cells. However, the increase in apoptosis during treatment did not correlate with the radiotracer tumoral uptake, even using more advanced image analysis (voxel-based analysis).
FML-10 PET imaging does not meet current clinical expectations for early detection of the therapeutic response to conventional chemotherapy. This review has pointed out the challenges of applying various apoptosis imaging strategies in clinical trials, the current methodologies available for image analysis and the future of molecular imaging to assess this therapeutic response.
Background
68
Ga-PSMA PET is the leading prostate cancer imaging technique, but the image quality remains noisy and could be further improved using an artificial intelligence-based denoising ...algorithm. To address this issue, we analyzed the overall quality of reprocessed images compared to standard reconstructions. We also analyzed the diagnostic performances of the different sequences and the impact of the algorithm on lesion intensity and background measures.
Methods
We retrospectively included 30 patients with biochemical recurrence of prostate cancer who had undergone
68
Ga-PSMA-11 PET-CT. We simulated images produced using only a quarter, half, three-quarters, or all of the acquired data material reprocessed using the SubtlePET® denoising algorithm. Three physicians with different levels of experience blindly analyzed every sequence and then used a 5-level Likert scale to assess the series. The binary criterion of lesion detectability was compared between series. We also compared lesion SUV, background uptake, and diagnostic performances of the series (sensitivity, specificity, accuracy).
Results
VPFX-derived series were classified differently but better than standard reconstructions (
p
< 0.001) using half the data. Q.Clear series were not classified differently using half the signal. Some series were noisy but had no significant effect on lesion detectability (
p
> 0.05). The SubtlePET® algorithm significantly decreased lesion SUV (
p
< 0.005) and increased liver background (
p
< 0.005) and had no substantial effect on the diagnostic performance of each reader.
Conclusion
We show that the SubtlePET® can be used for
68
Ga-PSMA scans using half the signal with similar image quality to Q.Clear series and superior quality to VPFX series. However, it significantly modifies quantitative measurements and should not be used for comparative examinations if standard algorithm is applied during follow-up.
Telomere length appears to correlate with survival in early non-small-cell lung cancer (NSCLC), but the prognostic impact of telomere status in advanced NSCLC remains undetermined. Our purpose was to ...evaluate telomere parameters as prognostic and predictive biomarkers in advanced NSCLC. In 79 biopsies obtained before treatment, we analyzed the telomere length and expression of
and shelterin complex genes (
,
,
,
,
, and
), using quantitative PCR. Non-responders to first-line chemotherapy were characterized by shorter telomeres and low
expression (
= 0.0035 and
= 0.0069), and tended to show higher
levels (
= 0.058). In multivariate analysis, short telomeres were associated with reduced event-free (EFS,
= 0.0023) and overall survival (OS,
= 0.00041).
and
overexpression correlated with poor EFS (
= 0.0069 and
= 0.00041) and OS (
= 0.0051 and
= 0.007). Low
and
expression-levels were linked to reduced EFS (
= 0.00032 and
= 0.0069) and OS (
= 0.000051 and
= 0.02). Short telomeres were also associated with decreased survival after nivolumab therapy (
= 0.097). Evaluation of telomere status in advanced NSCLC emerges as a useful biomarker that allows for the selection of patient groups with different clinical evolutions, to establish personalized treatment.
For more than a decade, DNA and histone methylations have been the focus of extensive work, although their relationship with methyl group metabolism was overlooked. Recently, it has emerged that ...epigenetic methylations are influenced by methyl donor nutrient availability, cellular levels of S-adenosyl-methionine (SAM), and cytoplasmic methyltransferase activities. SAM-dependent methyltransferases methylate a wide range of targets, from small molecules to proteins and nucleic acids. However, few investigations of the global methylome of tumors have been performed. Here, untargeted NMR metabolomics of two mouse tumor models labeled with 13C-methylmethionine were used to search for the NMR-visible set of cellular methyl acceptors denoted the global methylome. Tumor models were B16 melanoma cell cultures and B16 melanoma tumors, which may be considered as two stages of B16 tumor development. Based on 2D 1H–13C NMR spectra and orthogonal partial least squares discriminant analysis of spectra, our study revealed markedly different global methylomes for melanoma models. The methylome of B16 melanoma cell cultures was dominated by histone methylations, whereas that of B16 melanoma tumors was dominated by cytoplasmic small-molecule methylations. Overall, the technique gave access to the non-DNA methylome. Comparison of tumor models also exhibiting differential expression of aerobic glycolysis provided clues to a methyl metabolism shift during tumor progression.
(1) Background: As outcome of patients with metastatic melanoma treated with anti-PD1 immunotherapy can vary in success, predictors are needed. We aimed to predict at the patients' levels, overall ...survival (OS) and progression-free survival (PFS) after one year of immunotherapy, based on their pre-treatment 18F-FDG PET; (2) Methods: Fifty-six metastatic melanoma patients-without prior systemic treatment-were retrospectively included. Forty-five 18F-FDG PET-based radiomic features were computed and the top five features associated with the patient's outcome were selected. The analyzed machine learning classifiers were random forest (RF), neural network, naive Bayes, logistic regression and support vector machine. The receiver operating characteristic curve was used to compare model performances, which were validated by cross-validation; (3) Results: The RF model obtained the best performance after validation to predict OS and PFS and presented AUC, sensitivities and specificities (IC95%) of 0.87 ± 0.1, 0.79 ± 0.11 and 0.95 ± 0.06 for OS and 0.9 ± 0.07, 0.88 ± 0.09 and 0.91 ± 0.08 for PFS, respectively. (4) Conclusion: A RF classifier, based on pretreatment 18F-FDG PET radiomic features may be useful for predicting the survival status for melanoma patients, after one year of a first line systemic treatment by immunotherapy.
Introduction: Loco regional persistence or recurrence of differentiated thyroid cancer (DTC) is frequent despite initial thyroidectomy and radioactive iodine therapy (RAI). The aim of this study was ...to analyze the impact of a complementary adjuvant RAI (Ad-RAI) on disease recurrence following re-operation on patients with locally persistent or recurrent DTC. Patients and Methods: A retrospective study of 85 patients with DTC was conducted. All patients were initially treated with total thyroidectomy and RAI, and re-operated for a locally persistent or recurrent disease. Propensity score was calculated to predict the impact of Ad-RAI on survival after reoperation, and to reduce the bias of the limited sample size and the prognostic tests. Results: 49 (58%) patients were re-treated with Ad-RAI after re-operation while 36 (42%) were only followed up. Disease recurrence after re-treatment (re-operation ± Ad-RAI) was detected in 31 patients (36.5%). In multivariate analysis, age >55 years (HR: 3.9 1.6; 9.5; p < 0.00001) was the main poor prognostic factor for recurrence-free survival. Three parameters independently influenced the decision to administer ad-RAI: low number of previous RAI administrations, Nx before re-operation, and pTg > 30 μg/l. These parameters were incorporated in the Propensity score calculation. If ad-RAI tended to improve recurrence-free survival (median survival 17.4 vs. 10.9 months), adjustment using the Propensity score removed any difference between the groups (p = 0.54), confirming the limited value of ad-RAI. Conclusion: In patients with locally persistent or recurrent DTC, age is the main independent prognostic factor. Adjuvant RAI does not improve recurrence-free survival of DTC patients.
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