Purpose: The therapeutic management of rhabdomyosarcoma (RMS) is strongly dependent on initial staging. This study aimed to evaluate F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) as an adjunct to conventional imaging (CI) in the staging and follow-up of pediatric RMS. Materials and Methods: A total of 13 consecutive children and adolescents (12 males, 1 female; mean age, 9.6 years) with histologically proven RMS (10 alveolar, 3 embryonal), in whom FDG PET/CT was performed at staging and follow-up, were retrospectively included. In total, 35 FDG PET/CT were compared with CI (MRI, CT, and bone scintigraphy) performed with a less than a 15-day interval. Histologic data, follow-up (mean, 27 months), and the final judgment of a multidisciplinary tumor board were considered as the standard of reference for result interpretation. Results: At staging, FDG PET/CT revealed 1 RMS of the prostate missed by CI, and found 19 true-positive lymph node territories in 4 patients and 11 bone metastases in 3 patients, versus 12 and 3, respectively, with CI. Conversely, FDG PET/CT was less sensitive for detecting infracentimetric lung nodules in 1 patient. On the whole analysis, FDG PET/CT modified lymph node staging in 4 of 13 patients, bone involvement in 2 patients, and led to treatment alteration in 2 children. Conclusions: FDG PET/CT can be useful in staging and restaging pediatric RMS, especially for assessing lymph nodes and bone involvement, and for detecting unknown primary sites of RMS, with potential therapeutic strategy alteration.

Background: The aim of this study was to compare a commercial dosimetry workstation (PLANET® Dose) and the dosimetry approach (GE Dosimetry Toolkit® and OLINDA/EXM® V1.0) currently used in our department for quantification of the absorbed dose (AD) to organs at risk after peptide receptor radionuclide therapy with [¹⁷⁷Lu]Lu-DOTA-TATE. Methods: An evaluation on phantom was performed to determine the SPECT calibration factor variations over time and to compare the Time Integrated Activity Coefficients (TIACs) obtained with the two approaches. Then, dosimetry was carried out with the two tools in 21 patients with neuroendocrine tumours after the first and second injection of 7.2 ± 0.2 GBq of [¹⁷⁷Lu]Lu-DOTA-TATE (40 dosimetry analyses with each software). SPECT/CT images were acquired at 4 h, 24 h, 72 h and 192 h post-injection and were reconstructed using the Xeleris software (General Electric). The liver, spleen and kidneys masses and TIACs were determined using Dosimetry Toolkit® (DTK) and PLANET® Dose. The ADs were calculated using OLINDA/EXM® V1.0 and the Local Deposition Method (LDM) or Dose voxel-Kernel convolution (DK) on PLANET® Dose. Results: With the phantom, the 3D calibration factors showed a slight variation (0.8% and 3.3%) over time, and TIACs of 225.19 h and 217.52 h were obtained with DTK and PLANET® Dose, respectively. In patients, the root mean square deviation value was 8.9% for the organ masses, 8.1% for the TIACs, and 9.1% and 7.8% for the ADs calculated with LDM and DK, respectively. The Lin’s concordance correlation coefficient was 0.99 and the Bland–Altman plot analysis estimated that the AD value difference between methods ranged from − 0.75 to 0.49 Gy, from − 0.20 to 0.64 Gy, and from − 0.43 to 1.03 Gy for 95% of the 40 liver, kidneys and spleen dosimetry analyses. The dosimetry method had a minor influence on AD differences compared with the image registration and organ segmentation steps. Conclusions: The ADs to organs at risk obtained with the new workstation PLANET® Dose are concordant with those calculated with the currently used software and in agreement with the literature. These results validate the use of PLANET® Dose in clinical routine for patient dosimetry after targeted radiotherapy with [¹⁷⁷Lu]Lu-DOTA-TATE.

[¹⁷⁷Lu]Lu-DOTATATE has been approved for progressive and inoperable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that overexpress somatostatin receptors. The absorbed doses by limiting organs and tumors can be quantified by serial postinfusion scintigraphy measurements of the γ-emissions from ¹⁷⁷Lu. The objective of this work was to explore how postinfusion [¹⁷⁷Lu]Lu-DOTATATE dosimetry could influence clinical management by predicting treatment efficacy (tumor shrinkage and survival) and toxicity. Methods: Patients with GEP-NETs treated with [¹⁷⁷Lu]Lu-DOTATATE between 2016 and 2022 and who underwent dosimetry were included. Absorbed doses were calculated for healthy organs (liver, kidneys, bone marrow, and spleen) and tumors using PLANET Dose and the local energy deposition method based on serial posttreatment SPECT/CT. Up to 5 lesions per site were selected and measured on images collected at baseline and 3 mo after treatment end (measurement masked to the somatostatin receptor imaging uptake). For toxicity assessment, laboratory parameters were regularly monitored. Clinical data, including time to death or progression, were collected from the patients’ health records. Correlations between absorbed doses by organs and toxicity and between absorbed doses by lesions and tumor volume variation were studied using regression models. Results: In total, 35 dosimetric studies were performed in patients with mostly grade 2 (77%) tumors and metastases in liver (89%), lymph nodes (77%), and bone (34%), and 146 lesions were analyzed: 1–9 lesions per patient, mostly liver metastases (65%) and lymph nodes (25%). The median total absorbed dose by tumors was 94.4 Gy. The absorbed doses by tumors significantly decreased between cycles. The absorbed dose by tumors was significantly associated with tumor volume variation (P < 0.001) 3 mo after treatment end, and it was a significant prognostic factor for survival. Toxicity analysis showed a correlation between the decrease of hematologic parameters such as lymphocytes or platelet concentrations and the absorbed doses by the spleen or bone marrow. The mean absorbed dose by the kidneys was not correlated with nephrotoxicity during the studied period. Conclusion: In patients treated with [¹⁷⁷Lu]Lu-DOTATATE for GEP-NETs, tumor and healthy organ dosimetry can predict survival and toxicities, thus influencing clinical management. Visual Abstract

Purpose: For the development of new anti-cancer therapeutic radiopharmaceuticals, including alpha particle emitters, it is important to determine the contribution of targeted effects in irradiated cells, and also of non-targeted effects in non-irradiated neighboring cells because they may affect the therapeutic efficacy and contribute to side effects. Experimental Design: Here, we investigated the contribution of non-targeted cytotoxic and genotoxic effects in vitro and in vivo in (xenografted mice) during alpha (²¹²Pb/²¹²Bi, ²¹³Bi) and Auger (¹²⁵I) radioimmunotherapy (RIT). Results: Between 67 and 94% (alpha RIT) and 8 and 15% (Auger RIT) of cancer cells were killed by targeted effects, whereas 7-36% (alpha RIT) and 27-29% (Auger RIT) of cells were killed by non-targeted effects. We then demonstrated that the non-targeted cell response to alpha and Auger RIT was partly driven by lipid raft-mediated activation of p38 kinase and c-JUN N-terminal kinases (JNK). Reactive oxygen species also played a significant role in these non-targeted effects, as demonstrated by NF-kB activation and the inhibitory effects of antioxidant enzymes and radical scavengers. Compared with RIT alone, the use of RIT with ASMase inhibitor (imipramine) or with a lipid raft disruptor (e.g., methyl-beta-cyclodextrin or filipin) led to an increase in clonogenic cell survival in vitro and to larger tumors and less tissue DNA damage in vivo. These results were supported by an inhibitory effect of pravastatin on Auger RIT. Conclusions: Cell membrane-mediated non-targeted effects play a significant role during Auger and alpha RIT, and drugs that modulate cholesterol level, such as statins, could interfere with RIT efficacy.

This study’s aim was to develop our dosimetric methodology using a commercial workstation for the routine evaluation of the organs at risk during peptide receptor radionuclide therapy (PRRT) with 177Lu. First, planar and SPECT sensitivity factors were determined on phantoms. The reconstruction parameters were optimized by SPECT/CT image acquisition using a NEMA IEC phantom containing a 500 ml bottle of 177Lu, to simulate a kidney. The recovery coefficients were determined on various phantoms. For the red marrow, this was calculated using a NEMA IEC phantom that contained a centrally placed bottle of 80 ml of 177Lu (to model the L2-L4 red marrow) flanked by two 200 ml bottles with 177Lu to simulate the kidneys. Then, SPECT/CT images were acquired at 4, 24, 72, and 192 h after injection in 12 patients with neuroendocrine tumors who underwent PRRT with 177Lu-DOTATATE. SPECT data were reconstructed using the iterative ordered subset expectation maximization (OSEM) method, with six iterations and ten subsets, attenuation, scatter, recovery resolution corrections, and a Gaussian post-filter of 0.11 cm. The liver, spleen, kidneys, and red marrow dose per administered activity (AD/A admin) values were calculated with the Medical Internal Radiation Dose (MIRD) formalism and the residence times (Dosimetry toolkit® application) using standard and CT imaging-based organ masses (OLINDA/EXM® V1.0 software). Sensitivity factors of 6.11 ± 0.01 and 5.67 ± 0.08 counts/s/MBq were obtained with planar and SPECT/CT acquisitions, respectively. A recovery coefficient of 0.78 was obtained for the modeled L2–L4 red marrow. The mean AD/A admin values were 0.43 ± 0.13 mGy/MBq [0.27–0.91] for kidneys, 0.54 ± 0.58 mGy/MBq [0.12–2.26] for liver, 0.61 ± 0.13 mGy/MBq [0.42–0.89] for spleen, and 0.04 ± 0.02 mGy/MBq [0.01–0.09] for red marrow. The AD/A admin values varied when calculated using the personalized and standard organ mass, particularly for kidneys (p = 1 × 10−7), spleen (p = 0.0069), and red marrow (p = 0.0027). Intra-patient differences were observed especially in organs close to or including tumor cells or metastases. The obtained AD/A admin values were in agreement with the literature data. This study shows the technical feasibility of patient dosimetry in clinical practice and the need to obtain patient-specific information.

Aims To assess specific clinical criteria in patients with uveitis that are related to signs of sarcoidosis on ¹⁸F-labelled fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET). Methods Retrospective study of 54 consecutive patients with chronic uveitis for whom a PET scan was done because of suspected sarcoidosis, between July 2004 and December 2009. All the patients underwent a clinical examination, biological tests and a high-resolution CT of the chest. Results 17 of the 54 patients (31.5%) presented hypermetabolic foci on ¹⁸F-FDG-PET scan consistent with sarcoidosis. Among them eight patients (14.8%) underwent biopsy showing non-caseating granuloma. At the end of the study, 10 patients (18.5%) were considered as having a presumed sarcoidosis and seven patients (12.9%) as having indeterminate sarcoidosis. The increasing age at the diagnosis of uveitis (p=0.01), the presence of posterior synechiae (p=0.01) and a positive high-resolution CT of the chest (p=0.01) were significantly related to an abnormal PET scan. Conclusions Increasing age at the diagnosis of uveitis, the presence of posterior synechiae and the positivity of high-resolution chest CT are associated with ¹⁸F-FDG PET scan signs consistent with sarcoidosis.