Preoperative 11 C-Methionine PET-MRI in Pediatric Infratentorial Tumors.

PURPOSE: MRI is the main imaging modality for pediatric brain tumors, but amino acid PET can provide additional information. Simultaneous PET-MRI acquisition allows to fully assess the tumor and lower the radiation exposure. Although symptomatic posterior fossa tumors are typically resected, the patient management is evolving and will benefit from an improved preoperative tumor characterization. We aimed to explore, in children with newly diagnosed posterior fossa tumor, the complementarity of the information provided by amino acid PET and MRI parameters and the correlation to histopathological results. PATIENTS AND METHODS: Children with a newly diagnosed posterior fossa tumor prospectively underwent a preoperative 11 C-methionine (MET) PET-MRI. Images were assessed visually and semiquantitatively. Using correlation, minimum apparent diffusion coefficient (ADC min ) and contrast enhancement were compared with MET SUV max . The diameter of the enhancing lesions was compared with metabolic tumoral volume. Lesions were classified according to the 2021 World Health Organization (WHO) classification. RESULTS: Ten children were included 4 pilocytic astrocytomas, 2 medulloblastomas, 1 ganglioglioma, 1 central nervous system embryonal tumor, and 1 schwannoma. All lesions showed visually increased MET uptake. A negative moderate correlation was found between ADC min and SUV max values ( r = -0.39). Mean SUV max was 3.8 (range, 3.3-4.2) in WHO grade 4 versus 2.5 (range, 1.7-3.0) in WHO grade 1 lesions. A positive moderate correlation was found between metabolic tumoral volume and diameter values ( r = 0.34). There was no correlation between SUV max and contrast enhancement intensity ( r = -0.15). CONCLUSIONS: Preoperative 11 C-MET PET and MRI could provide complementary information to characterize pediatric infratentorial tumors.

Granulocyte Colony-Stimulating Factor Nanocarriers for Stimulation of the Immune System (Part I): Synthesis and Biodistribution Studies.

In the field of cancer immunotherapy, an original approach consists of using granulocyte colony-stimulating factor (G-CSF) to target and activate neutrophils, cells of the innate immune system. G-CSF is a leukocyte stimulating molecule which is commonly used in cancer patients to prevent or reduce neutropenia. We focused herein on developing a G-CSF nanocarrier which could increase the in vivo circulation time of this cytokine, keeping it active for targeting the spleen, an important reservoir of neutrophils. G-CSF-functionalized silica and gold nanoparticles were developed. Silica nanoparticles of 50 nm diameter were functionalized by a solid phase synthesis approach. The technology enabled us to incorporate multiple functionalities on the surface such as a PEG as hydrophilic polymer, DTPA as 111In chelating agent and G-CSF. The gold nanocarrier consisted of nanoparticles of 2-3 nm diameter elaborated with DTPA groups on the surface and functionalized with G-CSF. We studied the particle biodistribution in mice with special attention to organs involved in the immune system. The two nanocarriers with similar functionalization of surface showed different pathways in mice, probably due to their difference in size. Considering the biodistribution after G-CSF functionalization, we confirmed that the protein was capable of modifying the pharmacokinetics by increasing the nanocarrier concentration in the spleen, a reservoir of G-CSF receptor expressing cells.

Granulocyte-Colony Stimulating Factor Nanocarriers for Stimulation of the Immune System (Part II): Dose-Dependent Biodistribution and In Vivo Antitumor Efficacy in Combination with Rituximab.

The purpose of immuno-modulation is to increase or restore the action of immunocompetent cells against tumors with or without the use of monoclonal antibodies. The innate immune system is a key player in various pathological situations, but cells of this system appear to be inhibited or insufficiently active in malignancy or severe infectious diseases. The present study was designed to investigate therapeutic value of nanoparticles (NPs) coupled with bioactive hematopoietic growth factors acting on the innate immune system. The use of nanoparticles (NPs) allowing multimodal detection and multifunctional grafting are currently of great interest for theranostic purposes. In the present work, we have evaluated the impact of the number of granulocyte-colony stimulating factor (G-CSF) grafted on the surface on the NPs on the biodistribution in mice thanks to indium 111 radiolabeling. Furthermore, we have investigated whether grafted G-CSF NPs could stimulate the immune innate system and enhance the therapeutic efficacy of the monoclonal antibody rituximab in mice bearing human lymphoma xenografts. Following intravenous (i.v.) administration of NP-DTPA and NP-DTPA/G-CSF-X high levels of radioactivity were observed in the liver. Furthermore, spleen uptake was correlated with the number of G-CSF molecules grafted on the surface of the NPs. Combining NP-DTPA/G-CSF-34 with rituximab strongly reduced RL tumor growth compared to rituximab alone or in combination with conventional G-CSF + rituximab. The use of highly loaded G-CSF NPs as immune adjuvants could enhance the antitumor activity of therapeutic monoclonal antibodies by amplifying tumor cell destruction by innate immune cells.

Is [18F]-2-fluoro-2-deoxy-d-glucose (FDG) scintigraphy with non-dedicated positron emission tomography useful in the diagnostic management of suspected metastatic thyroid carcinoma in patients with no detectable radioiodine uptake?

OBJECTIVE: Dedifferentiation of thyroid cancer leads to an inability of thyroid cells to concentrate iodine. In these cases, imaging methods that allow an accurate detection of recurrence and/or metastases at an early stage are essential for an adequate management of patients. Positron emission tomography using [18F]-2-fluoro-2-deoxy-d-glucose and a dedicated (dPET-FDG) or non-dedicated (nPET-FDG) camera has been suggested as a potential tool for the detection of tumour foci. DESIGN AND METHODS: This prospective study was undertaken to evaluate nPET-FDG in 51 consecutive patients (18 men, 33 women) with differentiated thyroid cancer (33 papillary, 11 follicular, four insular and three oncocytic (Hurthle-cell) thyroid carcinomas). Selection criteria were high thyroglobulin (Tg) levels (>10 ng/ml off-levothyroxine treatment) and no detectable radioiodine uptake, on a whole body scan performed with a high dose, in the absence of iodine contamination. RESULTS: Results were interpreted in terms of assumed presence of tumoral tIssue. Sensitivity of nPET-FDG was similar to that of conventional imaging modalities (67%). False negative nPET-FDG (n=16) were observed mostly in cases of micro-lesions (lymph nodes or lung metastases). Conversely, nPET-FDG identified new tumoral sites in 11 cases. Better sensitivity was found for nPET-FDG in patients with Tg levels higher than 15 microg/l (P<0.05). On a patient basis, results of nPET-FDG were equivalent to that of dPET-FDG. Finally, nPET-FDG changed treatment strategy in seven patients. CONCLUSIONS: nPET-FDG has a high sensitivity for the detection of tumour sites in patients when pathological iodine uptake cannot be demonstrated and appears to be a useful method in patients with elevated Tg levels, especially when dedicated PET is either unavailable or impractical.