18F-FET and 18F-choline PET-CT in patients with MRI-suspected low-grade gliomas: a pilot study.

AIM: To investigate the diagnostic accuracy of O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) and fluoromethyl-(18F)-dimethyl-2-hydroxyethyl-ammonium chloride (18F-FCH) computed tomography (CT) in patients with primary low-grade gliomas (LGG). METHODS: The study enrolled patients with magnetic resonance imaging (MRI)-suspected LGG. Patients underwent both 18F-FET and 18F-FCH positron emission tomography (PET)-CT. Brain PET-CT was performed according to standard protocol - 20 minutes after intravenous injection of 185 MBq of 18F-FET and 185 MBq of 18F-FCH PET. Surgery and pathohistological diagnosis were performed in the next two weeks. RESULTS: We observed significantly better concordance between tumor histology and 18F-FET PET (weighted Kappa 0.74) compared with both 18F-FCH (weighted Kappa 0.15) and MRI (weighted Kappa 0.00). Tumor histology was significantly associated with 18F-FET (odds ratio 12.87; 95% confidence interval [CI], 0.49-333.70; P=0.013, logistic regression analysis). Receiver operating characteristic curve analysis comparing 18F-FCH (area under the curve [AUC] 0.625, 95% CI 0.298-0.884) and 18F-FET (AUC 0.833, 95% CI 0.499-0.982) showed better diagnostic properties of 18F-FET (AUC difference 0.208, 95% CI -0.145 to 0.562, P=0.248). CONCLUSION: Performing PET-CT in patients with newly diagnosed LGG should be preceded by a selection of an appropriate radiopharmaceutical. 18F-FET seems to be more accurate than 18F-FCH in the LGG diagnosis.

Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice.

PURPOSE: Iron overload accelerates bone loss in mice lacking the bone morphogenetic protein 6 (Bmp6) gene, which is the key endogenous regulator of hepcidin, iron homeostasis gene. We investigated involvement of other BMPs in preventing haemochromatosis and subsequent osteopenia in Bmp6-/- mice. METHODS: Iron-treated wild-type (WT) and Bmp6-/- mice were analysed for hepcidin messenger RNA (mRNA) and tissue and blood BMP levels by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), immunohistochemistry, Western blot, enzyme-linked immunosorbent assay (ELISA) and proximity extension assay. BMPs labeled with technetium-99m were used in pharmacokinetic studies. RESULTS: In WT mice, 4 h following iron challenge, liver Bmp6 and hepcidin expression were increased, while expression of other Bmps was not affected. In parallel, we provided the first evidence that BMP6 circulates in WT mice and that iron increased the BMP6 serum level and the specific liver uptake of (99m)Tc-BMP6. In Bmp6-/- mice, iron challenge led to blunted activation of liver Smad signaling and hepcidin expression with a delay of 24 h, associated with increased Bmp5 and Bmp7 expression and increased Bmp2, 4, 5 and 9 expression in the duodenum. Liver Bmp7 expression and increased circulating BMP9 eventually contributed to the late hepcidin response. This was further supported by exogenous BMP7 therapy resulting in an effective hepcidin expression followed by a rapid normalisation of plasma iron values and restored osteopenia in Bmp6-/- mice. CONCLUSION: In Bmp6-/- mice, iron activated endogenous compensatory mechanisms of other BMPs that were not sufficient for preventing hemochromatosis and bone loss. Administration of exogenous BMP7 was effective in correcting the plasma iron level and bone loss, indicating that BMP6 is an essential but not exclusive in vivo regulator of iron homeostasis.

Clinical utility of [68Ga]Ga-PSMA-11 PET/CT in initial staging of patients with prostate cancer and importance of intraprostatic SUVmax values.

BACKGROUND: As in disease recurrence, providing clinicians with the exact extent of the disease at the time of initial diagnosis is key in the management and individual treatment of prostate cancer (PC) patients. Intending to examine the usefulness of gallium- 68 PSMA-11 positron emission tomography/computed tomography ([68Ga]Ga-PSMA-11 PET/CT) and to determine if there is a correlation between prostate-specific antigen (PSA) serum values, WHO/ISUP (World Health Organization/International Society of Urological Pathology's) grade group of the tumor and SUVmax (maximized standardized uptake value) values we retrospectively analyzed PET/CT studies performed for initial staging of the disease. PATIENTS AND METHODS: We retrospectively evaluated 34 studies of patients who underwent [68Ga]Ga-PSMA-11 PET/CT as part of the initial staging of prostate cancer. All patients had prostate cancer confirmed by histological assessment after biopsy and had Gleason score and PSA serum values obtained. The mean PSA value was 33.8 ± 40.9 nmol/L (range 2.2-232). RESULTS: Nineteen patients had extended disease (55.9%). The mean SUVmax in prostate lesions was 19.5 ± 12.6. The mean value of SUVmax of PET studies in the high-risk group was significantly higher than those of low risk (23.5 ± 13.2 and 10.6 ± 5.4, p < 0.05). A positive correlation was observed between the ISUP group and SUVmax value of prostate lesions (Pearson's r = 0.557, p < 0.01). A positive correlation was also found in the comparison between PSA values and SUVmax (Pearson's r = 0.34, p < 0.05). CONCLUSIONS: In our study, [68Ga]Ga-PSMA-11 PET/CT scans detected the extended disease in more than half of the patients. Locating disease beyond the prostate gland allowed better informed clinical decisions and modified treatment. A positive correlation was found between intraprostatic SUVmax values and the ISUP group of prostate cancer. High-risk patients had SUVmax values that were significantly higher than those of low-risk patients. The correlation between the Gleason score and SUVmax value can be explained by the increased intensity of PSMA expression as the tumor grade increases.

The value of 18F-DOPA PET/CT in patients with medullary thyroid carcinoma and increased calcitonin values.

AIM: The aim of this prospective observational study was to examine the benefit of a fluorine-18-L-dihydroxyphenylalanine (F-DOPA) PET/computed tomography (CT) scan in patients with medullary thyroid carcinoma (MTC) in terms of increased calcitonin levels. PATIENTS AND METHODS: Twenty-eight MTC patients after initial total thyreoidectomy with increasing follow-up calcitonin levels suggestive for active disease after negative conventional imaging findings (neck ultrasound or thorax, abdomen, pelvis multislice computed tomography as standard imaging) were scanned using F-DOPA PET/CT from November 2012 to April 2016. The mean calcitonin level was 108.5 (range: 6.7-290) pmol/l and the mean carcinoembryonic antigen level was 15.7 (range: 1.1-221.9) µg/l. The mean follow-up period was 19.7 months. RESULTS: F-DOPA PET/CT was positive in 16 out of 28 (57%) patients, mostly because of metabolically active neck and mediastinal lymph nodes metastases. Previously unknown bone metastases were found in six patients. A positive scan was reported in four patients (25% of positive scans) with a very low calcitonin value of less than 49.9 pmol/l. PET/CT findings led to a change of management and therapy in 16 out of 28 patients, with surgical procedure performed in eight patients, radiotherapy in five patients, and chemotherapy in two patients. CONCLUSION: F-DOPA PET/CT is a clinically useful modality in MTC whenever the calcitonin level is increased. There is a clear trend toward more positive scans with the higher calcitonin values, but patients with moderately elevated calcitonin values should also be taken into consideration for molecular imaging with F-DOPA PET/CT as the tumor burden in these patients is probably low, enabling further therapy to be individualized and consequently more efficient.

[90Y-ibritumomab tiuxetan in patients with follicular lymphoma relapsing or refractory to rituximab]. / 90Y-ibritumomab tiuksetan u bolesnika s refraktornim folikularnim limfomom ili u relapsu nakon rituksimaba.

Radioimmunotherapy is a new antineoplastic treatment modality combining the effects of irradiation and monoclonal antibodies. 90Y-ibritumomab tiuxetan is a monoclonal antibody directed against the CD20 antigen to which a radioactive isotope of yttrium is attached, used for treating follicular lymphomas (FL). Using this compound we treated 8 patients with FL relapsing or refractory to combinations of rituximab and chemotherapy. Severe neutropenia developed in 5, and severe thrombocytopenia and anemia in 3 patients. Serious infections developed in 2 patients, one died. Six patients responded to treatment, 4 are still in remission after a median follow-up of 15 months, 2 died of lymphoma. Best response was achieved in low-risk patients with a low tumor burden. 90Y-ibritumomab tiuxetan is an effective treatment for FL with significant hematological toxicity and a high price.

The nonspecific lymph node uptake of 18F-choline in patients with prostate cancer--a prospective observational study.

BACKGROUND: The aim of this study was to observe and characterize the nonspecific ¹8F-choline lymph node uptake in patients with prostate cancer. MATERIAL AND METHODS: In this single center, prospective observational study which was done in University Hospital Center Zagreb between December 2012 and October 2014, 69 patients (median age 71 years; range 50-92) with prostate cancer were included. Patients underwent ¹8F-choline PET/CT for staging or restaging of prostate cancer. The mean follow-up period was 11.5 months. Kruskal-Wallis test was used to find out if the differences between SUV values of specific and nonspecific accumulation of the tracer are statistically significant. RESULTS: Nonspecific accumulation of ¹8F-choline in lymph nodes was found in 36 patients (52.7%). Most of these findings (n = 24) were nonspecific accumulation of the tracer in mediastinal lymph nodes. Other sites of nonspecific tracer uptake were pulmonary hila (n = 20), inguinal lymph nodes (n = 15), and axillary lymph nodes (n = 10). Mean SUV values for mediastinal lymph nodes, pulmonary hila, axillary and inguinal lymph nodes were 4.8, 4.3, 3.1 and 4.1, respectively. Mean SUV value of nonspecific sites of tracer accumulation was lower (not significantly; (p = 0.2) than tracer uptake values measured in metastases sites (bone metastases mean SUVmax value - 13.2, metastatic lymph nodes mean SUVmax value - 9.2). CONCLUSIONS: ¹8F-choline PET/CT is a valuable and an established functional diagnostic imaging method for staging and restaging prostate cancer. However, nonspecific uptake of the tracer can often be seen in lymph nodes not related to primary disease. Patient history, clinical examination, laboratory tests and correlation with other imaging methods, must be taken into consideration when interpreting ¹8F-choline PET/CT findings.

Usefulness of low iodine diet in managing patients with differentiated thyroid cancer - initial results.

BACKGROUND: Low iodine diet (LID) is recommended in patients with differentiated thyroid cancer before radioiodine administration. Patients with increased thyroglobulin (Tg) level, but negative (131)I whole body scan present diagnostic and therapeutic dilemma. This study was designed to evaluate the benefit of a two-week LID in patients with elevated serum Tg levels and negative (131)I whole body scans. PATIENTS AND METHODS.: For the impact assessment of two-week LID on radioiodine tissue avidity, radioiodine scans before and after LID were compared. Sixteen patients with serum Tg > 2 µg/L, negative Tg-antibodies, and negative radioiodine scans underwent two-week LID before the (131)I administration. Fourteen patients underwent diagnostic scanning and two patients received radioiodine therapy. Iodine concentration in the morning urine specimens were measured in each patient, a day before and 15(th) day after starting LID. RESULTS: Following self-managed LID, patients were able to significantly reduce their iodine body content by 50% (range 28-65%, p<0,001). 13 patients (82%) accomplished mild iodine deficiency (50-99 µg/L) and one patient (6%) achieved targeted moderate iodine deficient state (<50 µg/L). All diagnostic post-LID scans were negative. Both post-therapy (131)I scans showed radioiodine accumulation outside of normal (131)I distribution (neck region and diffuse hepatic uptake). This study demonstrated that two-week LID is effective way to decrease total body iodine content, although without a visible effect on post-LID diagnostic (131)I scans. CONCLUSIONS: A more stringent dietary protocol and longer iodine restriction period are probably needed to achieve targeted moderate iodine deficiency in patients preparing for (131)I administration. This might result in higher radioiodine avidity of thyroid remnant/metastases.