Lower 68 Ga-DOTATOC uptake in nonfunctioning pituitary neuroendocrine tumours compared to normal pituitary gland-A proof-of-concept study.

OBJECTIVES: 68  Ga-DOTATOC PET targets somatostatin receptors (SSTRs) and is well established for the detection of SSTR-expressing tumors, such as gastrointestinal neuroendocrine tumors. Pituitary adenomas, recently designated as pituitary neuroendocrine tumors (PitNETs), also express SSTRs, but there has been no previous evaluations of 68  Ga-DOTATOC PET in PitNET patients. The aim of this pilot study was to evaluate the diagnostic properties of 68  Ga-DOTATOC PET in the most common PitNET, ie non-functioning (NF)-PitNET. DESIGN/PATIENTS: NF-PitNET patients (n = 9) and controls (n = 13) were examined preoperatively with 68  Ga-DOTATOC PET for 45 min after tracer injection in dynamic list mode. Tumor specimens were collected during surgery in patients. MRI and PET images were co-registered using PMOD software. The maximum standard uptake value (SUVmax ) was analyzed in manually outlined regions of interest (ROI) around the tumor in patients and around the pituitary gland in controls. Immunohistochemical analyses were conducted on tumor specimens for assessment of tumor cell type and SSTR expression. RESULTS: Median SUVmax (IQR) was lower in patients than in controls (3.9 [3.4-8.5] vs 14.1 [12.5-15.9]; P < .01]. In ROC analysis, the area under the curve was 0.87 (P < .01) for SUVmax , with 78% sensitivity and 92% specificity. Immunohistochemical analysis showed NF-PitNETs were of gonadotroph (n = 7) and corticotroph (n = 2) origin. SSTR expression was high for SSTR3, low-to-moderate for SSTR2, and low for SSTR1 and SSTR5. CONCLUSIONS: This proof-of-concept study shows that 68 Ga-DOTATOC PET can be used to differentiate between normal pituitary tissue and NF-PitNET.

Linking loss of sodium-iodide symporter expression to DNA damage.

Radiotherapy of thyroid cancer with I-131 is abrogated by inherent loss of radioiodine uptake due to loss of sodium iodide symporter (NIS) expression in poorly differentiated tumor cells. It is also known that ionizing radiation per se down-regulates NIS (the stunning effect), but the mechanism is unknown. Here we investigated whether loss of NIS-mediated iodide transport may be elicited by DNA damage. Calicheamicin, a fungal toxin that specifically cleaves double-stranded DNA, induced a full scale DNA damage response mediated by the ataxia-telangiectasia mutated (ATM) kinase in quiescent normal thyrocytes. At sublethal concentrations (<1nM) calicheamicin blocked NIS mRNA expression and transepithelial iodide transport as stimulated by thyrotropin; loss of function occurred at a much faster rate than after I-131 irradiation. KU-55933, a selective ATM kinase inhibitor, partly rescued NIS expression and iodide transport in DNA-damaged cells. Prolonged ATM inhibition in healthy cells also repressed NIS-mediated iodide transport. ATM-dependent loss of iodide transport was counteracted by IGF-1. Together, these findings indicate that NIS, the major iodide transporter of the thyroid gland, is susceptible to DNA damage involving ATM-mediated mechanisms. This uncovers novel means of poor radioiodine uptake in thyroid cells subjected to extrinsic or intrinsic genotoxic stress.

Cardiovascular Magnetic Resonance in Myocarditis.

Myocarditis is an inflammatory disease of the myocardium, and its diagnosis remains challenging owing to a varying clinical presentation and broad spectrum of underlying aetiologies. In clinical practice, cardiovascular magnetic resonance has become an invaluable non-invasive imaging tool in the evaluation of patients with clinically suspected myocarditis, mainly thanks to its unique multiparametric tissue characterization ability. Although considered as useful, the method also has its limitations. This review aims to provide an up-to-date overview of the strengths and weaknesses of cardiovascular magnetic resonance in the diagnostic work-up of patients with clinically suspected myocarditis in a broad clinical context.

THE POTENTIAL TO USE TLD MEASUREMENTS TO VALIDATE THE OCCUPATIONAL RADIATION PROTECTION AT THE DEPARTMENT OF NUCLEAR MEDICINE.

Diagnostic examinations in nuclear medicine increase. This can cause a higher radiation burden to the personnel. The aim of this study was to create and apply a method to validate the occupational radiation protection at the Department of Nuclear Medicine using thermoluminescence dosemeters (TLD). Occupational doses in- and outside of the department and the dose rate distribution around the positron emission tomography/computed tomography (PET/CT) were validated in terms of Hp(10) using TLD-100. Backscatter correction factors were estimated to implement the TLD measurements on different materials. After correction for backscatter, the result indicates that doses in- and outside of the department are below recommended values and dose limits. The highest and the lowest dose rate were measured beside the 18F-autoinjector and the PET/CT gantry, respectively. The method of using TLD gives a good estimate of how the occupational radiation protection performs at the Department of Nuclear Medicine and can thus help in the optimization of radiation protection.

Intraperitoneal alpha-particle radioimmunotherapy of ovarian cancer patients: pharmacokinetics and dosimetry of (211)At-MX35 F(ab')2--a phase I study.

UNLABELLED: The alpha-emitter (211)At labeled to a monoclonal antibody has proven safe and effective in treating microscopic ovarian cancer in the abdominal cavity of mice. Women in complete clinical remission after second-line chemotherapy for recurrent ovarian carcinoma were enrolled in a phase I study. The aim was to determine the pharmacokinetics for assessing absorbed dose to normal tissues and investigating toxicity. METHODS: Nine patients underwent laparoscopy 2-5 d before the therapy; a peritoneal catheter was inserted, and the abdominal cavity was inspected to exclude the presence of macroscopic tumor growth or major adhesions. (211)At was labeled to MX35 F(ab')(2) using the reagent N-succinimidyl-3-(trimethylstannyl)-benzoate. Patients were infused with (211)At-MX35 F(ab')(2) (22.4-101 MBq/L) in dialysis solution via the peritoneal catheter. gamma-Camera scans were acquired on 3-5 occasions after infusion, and a SPECT scan was acquired at 6 h. Samples of blood, urine, and peritoneal fluid were collected at 1-48 h. Hematology and renal and thyroid function were followed for a median of 23 mo. RESULTS: Pharmacokinetics and dosimetric results were related to the initial activity concentration (IC) of the infused solution. The decay-corrected activity concentration decreased with time in the peritoneal fluid to 50% IC at 24 h, increased in serum to 6% IC at 45 h, and increased in the thyroid to 127% +/- 63% IC at 20 h without blocking and less than 20% IC with blocking. No other organ uptakes could be detected. The cumulative urinary excretion was 40 kBq/(MBq/L) at 24 h. The estimated absorbed dose to the peritoneum was 15.6 +/- 1.0 mGy/(MBq/L), to red bone marrow it was 0.14 +/- 0.04 mGy/(MBq/L), to the urinary bladder wall it was 0.77 +/- 0.19 mGy/(MBq/L), to the unblocked thyroid it was 24.7 +/- 11.1 mGy/(MBq/L), and to the blocked thyroid it was 1.4 +/- 1.6 mGy/(MBq/L) (mean +/- SD). No adverse effects were observed either subjectively or in laboratory parameters. CONCLUSION: This study indicates that by intraperitoneal administration of (211)At-MX35 F(ab')(2) it is possible to achieve therapeutic absorbed doses in microscopic tumor clusters without significant toxicity.

Stunning of iodide transport by (131)I irradiation in cultured thyroid epithelial cells.

UNLABELLED: The existence of thyroid stunning (i.e., inhibited thyroidal iodide uptake after administration of diagnostic amounts of (131)I) is controversial and is currently a subject of debate. To our knowledge, the stunning phenomenon has not been investigated previously in vitro. METHODS: Growth-arrested porcine thyroid cells that formed a tight and polarized monolayer in a bicameral chamber were irradiated with 3-80 Gy (131)I present in the surrounding culture medium for 48 h. The iodide transport capacity after irradiation was evaluated 3 d later by measuring the transepithelial (basal to apical) flux of trace amounts of (125)I. RESULTS: The basal-to-apical (125)I transport decreased with increasing absorbed dose acquired from (131)I; a nearly 50% reduction was observed already at 3 Gy. Stable iodide at the same molarity as (131)I (10(-8) mol/L) had no effect on the (125)I transport. Cell number and epithelial integrity were not affected by irradiation. CONCLUSION: Stunning of iodide transport is detected after (131)I irradiation of cultured thyroid cells. The degree of inhibition of transport is dependent on the absorbed dose.