Cédric Mathieu

Tumor Immunotargeting Using Innovative Radionuclides

This paper reviews some aspects and recent developments in the use of antibodies to target radionuclides for tumor imaging and therapy. While radiolabeled antibodies have been considered for many years in this context, only a few have reached the level of routine clinical use. However, alternative radionuclides, with more appropriate physical properties, such as lutetium-177 or copper-67, as well as alpha-emitting radionuclides, including astatine-211, bismuth-213, actinium-225, and others are currently reviving hopes in cancer treatments, both in hematological diseases and solid tumors. At the same time, PET imaging, with short-lived radionuclides, such as gallium-68, fluorine-18 or copper-64, or long half-life ones, particularly iodine-124 and zirconium-89 now offers new perspectives in immuno-specific phenotype tumor imaging. New antibody analogues and pretargeting strategies have also considerably improved the performances of tumor immunotargeting and completely renewed the interest in these approaches for imaging and therapy by providing theranostics, companion diagnostics and news tools to make personalized medicine a reality.

Laparoscopic Sentinel Lymph Node Versus Hyperextensive Pelvic Dissection for Staging Clinically Localized Prostate Carcinoma: A Prospective Study of 200 Patients

Lymph node metastasis is an important prognostic factor in prostate cancer (PC). The aim of this prospective study was to validate, through laparoscopic surgery, the accuracy of the isotopic sentinel lymph node (SLN) technique correlated with hyperextensive pelvic resection (extended pelvic lymphadenectomy dissection) in patients with localized PC, candidates for local curative treatment. Methods: A transrectal ultrasound-guided injection of 99mTc-sulfur rhenium colloid (0.3 mL/100 MBq) in each prostatic lobe was performed the day before surgery. Detection was performed intraoperatively with a laparoscopic probe, followed by extensive resection. SLN counts were performed in vivo and confirmed ex vivo. Histologic analysis was performed by hematoxylin-phloxine-safran staining, followed by immunohistochemistry if the SLN was free of metastasis. Results: Two hundred three patients with PC at intermediate or high risk of lymph node metastases were included. The intraoperative detection rate was 96% (195/203). Thirty-five patients had lymph node metastases, 19 only in the SLN. The false-negative rate was 8.5% (3/35). Unilateral surgical SLN detection did not validate bilateral pelvic lymph node status, and extended pelvic lymphadenectomy dissection was necessary on the opposite side of detection to minimize the false-negative rate (2.8% [1/35]). A significant metastatic sentinel invasion in the common iliac region existed (9.3%) but was always associated with other metastatic node areas. The internal iliac region was the primary metastatic site (40.7%). Finally, this series invalidated any justification for a standard or limited dissection, which would have missed 51.9% and 74.1% of lymph node metastases, respectively. Conclusion: The radioisotope SLN identification method up to the common iliac region is successful to identify sentinel nodes during laparoscopic surgery per hemipelvis to be acceptably considered as an isolated procedure and should be validated for intermediate- and high-risk patients.

Characterization of 18F-Fluorodeoxyglucose Uptake Pattern in Noninfected Prosthetic Heart ValvesCLINICAL PERSPECTIVE

Background— 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has been recently acknowledged as a diagnostic tool for prosthetic valve endocarditis, but its specificity is limited by uptake on noninfected valves. The objective of this study was to outline the main features of FDG uptake on PET/CT in patients with noninfected prosthetic heart valve (PHV). Methods and Results— Our institution’s PET/CT database was reviewed to identify patients with PHV, excluding those suspected of infection or who had received antibiotic treatment. PET indication, valve location, and type (biological/mechanical) and time from implantation were collected for each patient. Images with and without attenuation correction were considered for interpretation. The pattern of FDG uptake (absent, homogeneous, or heterogeneous) was recorded. Fifty-four PHVs (51 patients) were identified, including 32 biological valves. Indications for PET were oncology (n=26), suspicion of prosthetic valve endocarditis subsequently excluded (n=17), and history of vasculitis (n=11). A periprosthetic FDG uptake was present in 47 (87%) and 30 (56%) PHVs with and without attenuation correction, respectively, and the pattern was homogeneous in all but 4 (7%) and 3 (6%) PHVs, respectively. On quantitative analysis, maximum standardized uptake values was greater in mechanical than in biological valves (4.0 [2.4–8.0] versus 3.3 [2.1–6.1]; P=0.01) and in patients with vasculitis than in those referred for other indications. The uptake intensity did not differ before and 3 months after valve replacement. Conclusions— Noninfected PHVs frequently display homogeneous FDG uptake, which remains steady over time. Caution is, therefore, needed when interpreting FDG PET/CT in suspected prosthetic valve endocarditis, with specific attention to uptake pattern.

Story of Rubidium-82 and Advantages for Myocardial Perfusion PET Imaging.

Rubidium-82 has a long story, starting in 1954. After preclinical studies in dogs showing that myocardial uptake of this radionuclide was directly proportional to myocardial blood flow (MBF), clinical studies were performed in the 80s leading to an approval in the USA in 1989. From that time, thousands of patients have been tested and their results have been reported in three meta-analyses. Pooled patient-based sensitivity and specificity were, respectively, 0.91 and 0.90. By comparison with 99mTc-SPECT, 82Rb PET had a much better diagnostic accuracy, especially in obese patients with body mass index ≥30 kg/m2 (85 versus 67% with SPECT) and in women with large breasts. A great advantage of 82Rb PET is its capacity to accurately quantify MBF. Quite importantly, it has been recently shown that coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity. Moreover, coronary flow reserve is a functional parameter particularly useful in the estimate of microvascular dysfunction, such as in diabetes mellitus. Due to the very short half-life of rubidium-82, the effective dose calculated for a rest/stress test is roughly equivalent to the annual natural exposure and even less when stress-only is performed with a low activity compatible with a good image quality with the last generation 3D PET scanners. There is still some debate on the relative advantages of 82Rb PET with regard to 99mTc-SPECT. For the last 10 years, great technological advances substantially improved performances of SPECT with its accuracy getting closer to this of 82Rb/PET. Currently, the main advantages of PET are its capacity to accurately quantify MBF and to deliver a low radiation exposure.

Assessment of Lymph Nodes and Prostate Status Using Early Dynamic Curves with 18F-Choline PET/CT in Prostate Cancer

Introduction Dynamic image acquisition with 18F-Choline [fluorocholine (FCH)] PET/CT in prostate cancer is mostly used to overcome the bladder repletion, which could obstruct the loco-regional analysis. The aim of our study was to analyze early dynamic FCH acquisitions to define pelvic lymph node or prostate pathological status. Material and methods Retrospective analysis was performed on 39 patients for initial staging (n = 18), or after initial treatment (n = 21). Patients underwent 10-min dynamic acquisitions centered on the pelvis, after injection of 3–4 MBq/kg of FCH. Whole-body images were acquired about 1 h after injection using a PET/CT GE Discovery LS (GE-LS) or Siemens Biograph mCT (mCT). Maximum and mean SUV according to time were measured on nodal and prostatic lesions. SUVmean was corrected for partial volume effect (PVEC) with suitable recovery coefficients. The status of each lesion was based on histological results or patient follow-up (>6 months). A Mann–Whitney test and ANOVA were used to compare mean and receiver operating characteristic (ROC) curve analysis. Results The median PSA was 8.46 ng/mL and the median Gleason score was 3 + 4. Ninety-two lesions (43 lymph nodes and 49 prostate lesions) were analyzed, including 63 malignant lesions. In early dynamic acquisitions, the maximum and mean SUV were significantly higher, respectively, on mCT and GE-LS, in malignant versus benign lesions (p < 0.001, p < 0.001). Mean SUV without PVEC, allowed better discrimination of benign from malignant lesions, in comparison with maximum and mean SUV (with PVEC), for both early and late acquisitions. For patients acquired on mCT, area under the ROC curve showed a trend to better sensitivity and specificity for early acquisitions, compared with late acquisitions (SUVmax AUC 0.92 versus 0.85, respectively). Conclusion Assessment of lymph nodes and prostate pathological status with early dynamic imaging using PET/CT FCH allowed prostate cancer detection in situations where proof of malignancy is difficult to obtain.

Response by Mathieu et al to Letter Regarding Article, “Characterization of 18 F-Fluorodeoxyglucose Uptake Pattern in Noninfected Prosthetic Heart Valves”

We thank Scholtens et al for their comments on our article.1 They rightly noticed that in Figure 3, the highest Standardized Uptake Value was observed in 2 patients with a history of vasculitis. Among factors potentially promoting inflammation in the vicinity of the sewing rings, they questioned the role of active disease and the presence of surgical material, such as bioadhesive. Reconstruction procedures were all performed in agreement with EANM Research Ltd accreditation recommendations. Although the results were expressed as Standardized Uptake Value max instead …

0049: FDG-PET imaging for the management of suspected inflammatory cardiomyopathies beyond cardiac sarcoidosis: a single center initial experience

Purpose FDG-positron emission tomography (PET) has high diagnostic accuracy in cardiac sarcoidosis (CS). Beyond CS, the non invasive diagnosis of inflammatory cardiomyopathies (IC) is challenged by a lower diagnostic performance of usual tools as magnetic resonance imaging (MRI). Methods 17 consecutive patients with suspected IC had a FDG-PET to detect myocardial inflammation. From all clinical data including PET, we classified patients in either CS or non-CS and respective PET data were compared. The clinical impact of adding PET in the non-CS group was evaluated by comparing diagnosis and management proposed by an expert blind to PET with final diagnosis and management actually held in practice. Results 6 patients had CS, all with positive PET. In the 11 non-CS patients, 7 had a positive PET. All had MRI late gadolinium enhancement in FDG uptake areas, suggesting a true positivity of PET for the presence of inflammation. PET data were all significantly different between CS and nonCS patients with positive PET, particularly the coefficient of variation of cardiac SUV which is an index of heterogeneity of FDG uptake was significantly greater in CS patients (0,4 vs 0,17 p Conclusion Some patients with suspected IC had a positive FDG-PET in favour of myocardial inflammation, with a different pattern from that observed in CS. Adding PET to usual diagnostic tools led to a decrease of possible IC diagnosis that turned in excluded IC. These preliminary data suggest a potential role of PET for the non-invasive diagnosis of IC that will need further investigations. Download : Download high-res image (89KB) Download : Download full-size image Abstract 0049 – Figure: FDG uptake concordant with MRI-LGE