Anna Nardelli

F-18 FDG PET/CT quantization parameters as predictors of outcome in patients with diffuse large B-cell lymphoma

We evaluated the prognostic significance of standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) obtained by F‐18 FDG PET/CT (PET/CT) in patients with diffuse large B‐cell Lymphomas (DLBCL) presenting intermediate IPI score.

Assessment of Metabolic Response to Radioimmunotherapy with 90Y–Ibritumomab Tiuxetan in Patients with Relapsed or Refractory B-Cell Non–Hodgkin Lymphoma

PURPOSE To prospectively compare the assessment of metabolic response to yttrium 90 ((90)Y)-ibritumomab tiuxetan radioimmunotherapy (RIT) by using fluorine 18 ((18)F) fluorodeoxyglucose (FDG) combined positron emission tomographic-computed tomographic (PET/CT) imaging at 2 and 6 months to determine the most appropriate time to detect therapeutic response in refractory non-Hodgkin lymphoma (NHL) patients treated with RIT. MATERIALS AND METHODS The ethical committee of the university approved the protocol and all patients signed informed consent. Twenty-three consecutive patients (10 women, 13 men; mean age, 51.8 years +/-7.3 [standard deviation]) treated by using RIT for relapsed or refractory follicular NHL were enrolled. For all patients, (18)F FDG PET/CT scanning was performed at baseline and at 2 and 6 months after RIT. Response was assessed by using the International Workshop Criteria (IWC) and revised criteria (IWC + PET) as well as the criteria of the European Organization for Research and Treatment of Cancer. One-way analysis of variance for repeated measures, receiver operator curve analysis, and Kaplan-Meier curves were used for statistical analysis. RESULTS PET/CT performed at 2 months revealed complete (n = 12) or partial (n = 4) metabolic response in 16 of 23 patients with complete or partial clinical response. These findings were all confirmed at 6-month scanning. PET/CT indicated refractory or persistent disease at 2 and 6 months in the remaining seven patients. Better overall survival was observed for patients with a reduction in the maximum standard uptake value of 49% or higher (both at 2 and 6 months after RIT) when compared with those with a decrease of less than 49% (P < .05). CONCLUSION Early assessment of response to RIT by using PET/CT might be useful in the identification of patients needing additional therapeutic strategies.

Assessment of metabolic activity by PET-CT with F-18-FDG in patients with T-cell lymphoma

Complete List of Authors: Storto, Giovanni; IRCCS CROB, Nuclear Medicine Di Giorgio, Eugenio; Instituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche (CNR), Nuclear Medicine De Renzo, Amalia; Universita “Federico II”, Dipartimento di Biochimica e Biotecnologie Mediche Micol, Laura; Fondazione Istituto di Diagnostica Nucleare (SDN), Radiology Cerciello, Giuseppe; Universita “Federico II”, Dipartimento di Biochimica e Biotecnologie Mediche Nardelli, Anna; Instituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche (CNR), Nuclear Medicine Capacchione, Daniela; IRCCS CROB, Nuclear Medicine Castaldi, Elena; Instituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche (CNR), Nuclear Medicine Ortosecco, Giovanni; Instituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche (CNR), Nuclear Medicine pace, leonardo; universita Federico II, Radiology

Fully automated synthesis procedure of 4-[18F]fluorobenzaldehyde by commercial synthesizer: Amino-oxi peptide labelling prosthetic group

Automatic synthesis of 4-[18F]fluorobenzaldehyde has been developed by a commercially available TRACERlab FX(F-N) synthesis module to be used as prosthetic group for amino-oxy functionalized peptide labelling in clinical routine application. In addition a handmade purification device (HPD) has been setup to perform automatic cartridge purification as well as to back-up the reactor where one-pot synthesis is not applicable. Cartridges for solid phase extraction such as C18, C8, phenyl has been tested to best perform purification as well as activity recovery. Radiochemical yield (RCY) at end of synthesis (EOS) was in average 67% after about 45 min (90% decay corrected at EOB). The RCY of the entire procedure was 54% with a radiochemical purity above 99%.

Inhibition of AQP1 Hampers Osteosarcoma and Hepatocellular Carcinoma Progression Mediated by Bone Marrow-Derived Mesenchymal Stem Cells.

The complex cross-talk between tumor cells and their surrounding stromal environment plays a key role in the pathogenesis of cancer. Among several cell types that constitute the tumor stroma, bone marrow-derived mesenchymal stem cells (BM-MSCs) selectively migrate toward the tumor microenvironment and contribute to the active formation of tumor-associated stroma. Therefore, here we elucidate the involvement of BM-MSCs to promote osteosarcoma (OS) and hepatocellular carcinoma (HCC) cells migration and invasion and deepening the role of specific pathways. We analyzed the function of aquaporin 1 (AQP1), a water channel known to promote metastasis and neoangiogenes. AQP1 protein levels were analyzed in OS (U2OS) and HCC (SNU-398) cells exposed to conditioned medium from BM-MSCs. Tumor cell migration and invasion in response to BM-MSC conditioned medium were evaluated through a wound healing assay and Boyden chamber, respectively. The results showed that the AQP1 level was increased in both tumor cell lines after treatment with BM-MSC conditioned medium. Moreover, BM-MSCs-mediated tumor cell migration and invasion were hampered after treatment with AQP1 inhibitor. These data suggest that the recruitment of human BM-MSCs into the tumor microenvironment might cause OS and HCC cell migration and invasion through involvement of AQP1.

[F-18] FDG-PET/CT parameters as predictors of outcome in inoperable NSCLC patients.

Abstract Background. We evaluated the prognostic significance of standardized uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) in [F-18] FDG PET/CT findings in patients with inoperable non-small-cell lung cancer (NSCLC). Patients and methods. One hundred and three patients (mean age, 65.6 ± 16 years) underwent [F-18] FDG PET/CT before the chemotherapy. The SUVmax value, the MTV (cm3; 42% threshold) and the TLG (g) were registered. The patients were followed up to 18 months thereafter (range 12-55 months). Failure to respond without progression, progression and/or disease-related death constituted surrogate end-points. The optimal SUVmax, MTV and TLG cut-off to predict the patients’ outcome were estimated. PET/CT results were then related to disease outcome (progression free survival; PFS). Results. The Kaplan-Meier survival analysis for SUVmax showed a significant shorter PFS in patients presenting with lower values as compared to those with higher (p < 0.05, log-rank test). MTV and TLG were not suitable for predicting PFS apart from the subset of patients with mediastinal nodal involvement. Conclusions. Despite the availability of new tools for the quantitative assessment of disease activity on PET/CT, the SUVmax rather than MTV and TLG remains the only predictor for PFS in NSCLC patients. MTV holds a value only when concomitant nodal involvement occurs.

Therapeutic Strategies in HCC: Radiation Modalities

Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with 131I Lipiodol or 90Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment.

Impact of 18F-fluoride PET-CT on implementing early treatment of painful bone metastases with Sm-153 EDTMP

UNLABELLED This study evaluated the diagnostic impact of using skeletal (18)F-fluoride PET/CT on patients with painful bone metastases to schedule an early palliative radionuclide treatment. METHODS The skeletal involvement from prostate cancer metastases was assessed by both (99m)Tc-diphosphonate bone scan (BS) and (18)F-fluoride PET/CT within four weeks in 24 patients (67.7 ± 5.1 years) suffering from a borderline degree of bone pain for which radionuclide palliation was not shortly planned for administration. The BS and (18)F-fluoride PET/CT results were compared, assessing the number and extension of the skeletal sites involved. Afterward, the patients were randomly assigned either to the study group (N=12) receiving radionuclide therapy (Samarium-153 EDTMP) or to the control group (N=12) not receiving radionuclide therapy. The short-term results from the radionuclide palliation group (evaluated with a visual analogue scale) were compared with the controls. RESULTS Overall, at BS, 7.6 ± 1.4 sites were considered metastatic, involving at least 5 ± 1 body regions. At (18)F-fluoride PET/CT, 116 ± 19 sites presented metastatic involvement with 12/12 body regions concerned. No differences were found in regards to either the number of metastatic sites or regions at both BS and (18)F-fluoride PET/CT between the study group and controls (p=ns). At CT, 88 blastic metastases were identified, whereas 110 were mainly lytic. Most of mainly lytic lesions were not detectable at BS. The reduction in total discomfort and bone pain in the study group was significantly greater than in the controls (p<0.0001). CONCLUSION Sm-153 EDTMP therapy should be considered for patients with early bone pain from prostate cancer even if their BS only indicates a few metastases before the initiation of a severe pain syndrome. (18)F-fluoride PET/CT may be helpful in deciding if the implementation of bone pain palliation using bone-seeking radionuclides at pain onset is necessary.

F-18 FDG PET/CT metabolic tumor volume predicts overall survival in patients with disseminated epithelial ovarian cancer

OBJECTIVE We evaluated the prognostic impact of quantitative assessment by maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG) on [F-18] FDG PET/CT for patients with peritoneal carcinomatosis from epithelial ovarian cancer (EOC). METHODS Thirty-one patients with EOC underwent PET/CT for an early restaging after cytoreductive surgery, having been diagnosed with carcinomatosis (before chemotherapy). The SUVmax, MTV (cm3; 42% threshold) and TLG (g) were registered on residual peritoneal lesions. The patients were followed up 20±12months thereafter. The PET/CT results were compared to overall survival (OS). RESULTS The Kaplan-Meier survival analysis for the SUVmax did not reveal significant differences in OS (p=0.48). The MTV survival analysis showed a significant higher OS in patients presenting with a higher tumour burden than those with less tumour burden (p=0.01; 26 vs. 14 months), whereas TLG exhibited a similar trend though not significant (p=0.06). Apart from chemo-resistance, the higher the MTV, the better will be the response to chemotherapy. CONCLUSIONS Quantitative assessment by MTV rather than by SUVmax and TLG on PET/CT may be helpful for stratifying patients who present with peritoneal carcinomatosis from EOC, in order to implement the appropriate therapeutic regimen.

Enhancement of reaction conditions for the radiolabelling of DOTA-peptides with high activities of yttrium-90

UNLABELLED Peptide receptor radionuclide therapy (PRRT) has recently expanded due to radiolabelling of DOTA-peptides, such as the somatostatin analogues [DOTA(0), Tyr(3)]octreotate (DOTATATE). The achievement of high specific activities during procedures has been indicated as the critical factor to consent effective therapy. Several radiochemical factors may negatively impact reaction procedures such as pH, temperature and time of reaction. Our study was undertaken to explore the influence of radiochemical parameters, such as time of incubation, on reaction kinetics during the radiolabelling of DOTATATE with (90)Y. METHODS Forty-five radiolabelling procedures were carried out using small volumes of yttrium-90, typically 60-78 μL. At nearly constant pH and temperature two different settings of radiolabelling procedures were implemented, removing the products from the heating water bath approximately after 30 min (group E, early; n=20) and after 39 min (group L, later; n=25). Quality controls were performed by means of both high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). RESULTS Reaction kinetics for (90)Y were found to a provide suitable percentage of incorporation at pH 4.5 for both groups. Reaction temperature was not different between groups E and L. A significant difference was found between the two groups in radiochemical yield, which was 95.6% ± 0.8 for group E and 98.2% ± 1.1 for group L (p<0.0001). The specific activity of the final product was 46.9 MBq/nmol. CONCLUSION In order to achieve optimal specific activities, pH, temperature and time of reaction necessitate careful evaluation and setting. A statistically significant difference in labelling yield was found between a set of procedures completed at 39 min as compared to that executed at 30 min, keep the reaction pH and temperature constant.