Occupational exposure in the work process of radiology technologists with 68Ga-labeled radiopharmaceuticals.

The study identified occupational exposure in the work of radiology technologists with 68Ga radiopharmaceuticals, in a Nuclear Medicine service in southern Brazil, by means of observation and document analysis. The occupational exposure related the factors, distance, time and shielding. Thus, it was observed high times during handling of the material, small distances between sources and radiosensitive structures, such as the eye lens and the thyroid gland. It is recommended to reassess and standardize the work, once that critical moments should not be restricted only to dosimetric reading.

Treatment outcomes of metastasis-directed treatment using 68Ga-PSMA-PET/CT for oligometastatic or oligorecurrent prostate cancer: Turkish Society for Radiation Oncology group study (TROD 09-002).

PURPOSE: The aim of this study was to evaluate the outcomes of 68Ga prostate-specific membrane antigen (68Ga-PSMA) positron-emission tomography (PET)/CT-based metastasis-directed treatment (MDT) for oligometastatic prostate cancer (PC). METHODS: In this multi-institutional study, clinical data of 176 PC patients with 353 lesions receiving MDT between 2014 and 2019 were retrospectively evaluated. All patients had biopsy proven PC with ≤5 metastases detected with 68Ga-PSMA-PET/CT. MDT was delivered with conventional fractionation or stereotactic body radiotherapy (SBRT) techniques. CTCAE v4.0 was used for acute and RTOG/EORTC Late Radiation Morbidity Scoring Schema was used for late toxicity evaluation. RESULTS: At the time of MDT, 59 patients (33.5%) had synchronous and 117 patients (66.5%) had metachronous metastases. Median number of metastases was one and the MDT technique was SBRT in 73.3% patients. The 2­year overall survival (OS) and progression-free survival (PFS) rates were 87.6% and 63.1%, respectively. With a median follow-up of 22.9 months, 9 patients had local recurrence at the irradiated site. The 2­year local control rate at the treated oligometastatic site per patient was 93.2%. In multivariate analysis, an increased number of oligometastases and untreated primary PC were negative predictors for OS; advanced clinical tumor stage, untreated primary PC, BED3 value of ≤108 Gy, and MDT with conventional fractionation were negative predictors for PFS. No patient experienced grade ≥3 acute toxicity, but one patient had a late grade 3 toxicity of compression fracture after spinal SBRT. CONCLUSION: 68Ga-PSMA-PET/CT-based MDT is an efficient and safe treatment for oligometastatic PC patients. Proper patient selection might improve treatment outcomes.

Clinical Application of 18F-AlF-NOTA-Octreotide PET/CT in Combination With 18F-FDG PET/CT for Imaging Neuroendocrine Neoplasms.

OBJECTIVES: The study is to evaluate biodistribution, dosimetry, safety, and clinical usefulness of F-AlF-NOTA-octreotide (F-OC) PET/CT in combination with F-FDG PET/CT for detection of neuroendocrine neoplasms (NENs). METHODS: The biodistribution, dosimetry, and safety of F-OC were evaluated in 3 healthy volunteers. Twenty-two NEN patients underwent PET/CT at 60 minutes after intravenous injection of 3.7 to 4.44 MBq (0.1-0.12 mCi) per kilogram of body weight of F-OC. This was followed by F-FDG PET/CT within a 2-week period. RESULTS: F-OC was well tolerated by all healthy volunteers and NEN patients. The calculated effective dose of F-OC was 0.023 ± 0.002 mSv/MBq. In NEN patients, we observed prominent F-OC tumor uptake and high tumor-to-background ratios. Tumor uptake of F-OC was greater than that of F-FDG, and this was particularly evident in G2 NENs (median SUVmax, 45.6 vs 4.3; P < 0.015). Tumor uptake of F-OC or F-FDG was significantly correlated with tumor differentiation (P < 0.05). Dual tracer PET/CT detected more lesions and also yielded information on the biological status of tumors. CONCLUSIONS: The tracer F-OC exhibited favorable safety and dosimetry profiles. F-OC provided superior imaging of well-differentiated NENs and significantly higher tumor-to-background ratio compared with F-FDG. Combining F-FDG with F-OC PET/CT has the potential to improve NEN staging and management of patient treatment.

OCCUPATIONAL RADIATION DOSE TO NUCLEAR MEDICINE STAFF DUE TO TC99M, F18-FDG PET AND THERAPEUTIC I-131 BASED EXAMINATIONS.

The aim was to track the exposure to radiation workers in six nuclear medicine examinations. A number of 180 patients were recruited and external exposure was measured. Patients had undergone cardiac stress and rest, bone scan, I-131 therapy, Gallium-67 and FDG PET/CT imaging. The average dose received due to cardiac stress and rest were 20.4 ± 5.0 and 16.0 ± 3.8 µSv per patient, respectively, whereas for bone scan, Ga-67, FDG and I-131 therapy, the average dose was 6.1 ± 2.5, 6.0 ± 1.4, 11.1 ± 2.2 and 4.1 ± 2.6 µSv per patient. The patient-to-staff dose coefficients were on average 0.051 ± 0.009, 0.042 ± 0.010, 0.034 ± 0.016, 0.039 ± 0.021, 0.052 ± 0.012, 0.094 ± 0.021 µSv m2/MBq h for stress, rest, bone, I-131, Ga-67 and FDG reported post-administration, respectively. Patient injection and setup for imaging represent a high percentage of the total dose received by staff. The information revealed is able to revise local measures, safety standards, and could help further in dose optimization and minimal exposure to occupationally exposed worker in nuclear medicine laboratories.

Biodistribution and radiation dose estimates for 68Ga-DOTA-JR11 in patients with metastatic neuroendocrine tumors.

PURPOSE: Somatostatin receptor antagonists have shown promise for imaging neuroendocrine tumors (NETs) in preclinical studies, but clinical data is still very limited. In this study, we assess the feasibility of using the novel somatostatin antagonist 68Ga-DOTA-JR11 for PET imaging of NETs. METHODS: Twenty patients with advanced NETs underwent whole-body PET/CT imaging 60 min after injection of 169 MBq (median) 68Ga-DOTA-JR11 as part of a prospective study. Volumes of interest were drawn around up to four 68Ga-DOTA-JR11-avid lesions per patient (with uptake greater than liver) and standardized uptake values were estimated. Additionally, target-to-normal tissue ratios were calculated. A subset of six patients had additional imaging (25-min dynamic scan of the upper abdomen including, at least partly, cardiac left ventricle, liver, spleen, and kidney, and a whole-body PET/CT scan at 30 min post-injection) to determine the time course of tracer distribution and facilitate radiation dose estimates. Absorbed doses were calculated using OLINDA/EXM 1.0. RESULTS: In contrast to the known biodistribution of somatostatin receptor agonists, little or no uptake above background was seen in the pituitary gland, spleen, adrenals, and uninvolved liver; e.g., median spleen SUVmean 1.4 (range: 0.7-1.8), liver SUVmean 1.1 (0.7-1.9). A total of 42 tumor lesions were analyzed with median SUVmax 13.0 (range: 2.9-94), TNR blood 9.3 (1.8-87), TNR spleen 4.9 (1.9-48), TNR kidney 2.2 (0.52-28), and TNR liver 10.5 (2.3-107). Tumor uptake reached plateau levels by 20-30 min post-injection. The highest absorbed dose estimates (mGy/MBq) to normal tissues were: urinary bladder wall (0.30; SD 0.06) and kidneys (0.050; SD 0.013). The effective dose (ICRP 103) was 0.022 (SD 0.003) mSv/MBq. CONCLUSIONS: 68Ga-DOTA-JR11 demonstrated rapid tumor uptake, high tumor/background ratios, and rapid clearance from blood. The low liver background is advantageous and may facilitate detection of liver metastases. Dosimetric data compare favorably with published data for 68Ga-DOTATATE and 68Ga-DOTATOC.

Monosodium Glutamate Reduces 68Ga-PSMA-11 Uptake in Salivary Glands and Kidneys in a Preclinical Prostate Cancer Model.

We evaluated the ability of monosodium glutamate (MSG) to reduce salivary and kidney uptake of a prostate-specific membrane antigen (PSMA) radioligand without affecting tumor uptake. Methods: LNCaP tumor-bearing mice were intraperitoneally injected with MSG (657, 329, or 164 mg/kg) or phosphate-buffered saline (PBS). Fifteen minutes later, the mice were intravenously administered 68Ga-PSMA-11. PET/CT imaging and biodistribution studies were performed 1 h after administration. Results: Tumor uptake (percentage injected dose per gram [%ID]) was not statistically different between groups, at 8.42 ± 1.40 %ID in the 657 mg/kg group, 7.19 ± 0.86 %ID in the 329 mg/kg group, 8.20 ± 2.44 %ID in the 164 mg/kg group, and 8.67 ± 1.97 %ID in the PBS group. Kidney uptake was significantly lower in the 657 mg/kg group (85.8 ± 24.2 %ID) than in the 329 mg/kg (159 ± 26.2 %ID), 164 mg/kg (211 ± 27.4 %ID), and PBS groups (182 ± 33.5 %ID) (P < 0.001). Salivary gland uptake was lower in the 657 mg/kg (3.72 ± 2.12 %ID) and 329 mg/kg (5.74 ± 0.62 %ID) groups than in the PBS group (10.04 ± 2.52 %ID) (P < 0.01). Conclusion: MSG decreased salivary and kidney uptake of 68Ga-PSMA-11 in a dose-dependent manner, whereas tumor uptake was unaffected.

Focal MRI-Guided Salvage High-Dose-Rate Brachytherapy in Patients With Radiorecurrent Prostate Cancer.

INTRODUCTION: Whole-gland salvage treatment of radiorecurrent prostate cancer has a high rate of severe toxicity. The standard of care in case of a biochemical recurrence is androgen deprivation treatment, which is associated with morbidity and negative effects on quality of life. A salvage treatment with acceptable toxicity might postpone the start of androgen deprivation treatment, might have a positive influence on the patients' quality of life, and might even be curative. Here, toxicity and biochemical outcome are described after magnetic resonance imaging-guided focal salvage high-dose-rate brachytherapy in patients with radiorecurrent prostate cancer. MATERIALS AND METHODS: Seventeen patients with pathologically proven locally recurrent prostate cancer were treated with focal high-dose-rate brachytherapy in a single 19-Gy fraction using magnetic resonance imaging for treatment guidance. Primary radiotherapy consisted of external beam radiotherapy or low-dose-rate brachytherapy. Tumors were delineated with Ga-68-prostate-specific membrane antigen or F18-choline positron emission tomography in combination with multiparametric magnetic resonance imaging. All patients had a prostate-specific antigen level of less than 10 ng/mL at the time of recurrence and a prostate-specific antigen doubling time of ≥12 months. Toxicity was measured by using the Common Terminology Criteria for Adverse Events version 4. RESULTS: Eight of 17 patients had follow-up interval of at least 1 year. At a median follow-up interval of 10 months (range 3-40 months), 1 patient experienced a biochemical recurrence according to the Phoenix criteria, and prostate-specific membrane antigen testing revealed that this was due to a distant nodal metastasis. One patient had a grade 3 urethral stricture at 2 years after treatment. CONCLUSION: Focal salvage high-dose-rate brachytherapy in patients with radiorecurrent prostate cancer showed grade 3 toxicity in 1 of 17 patients and a distant nodal metastasis in another patient. Whether this treatment option leads to cure in a subset of patients or whether it can successfully postpone androgen deprivation treatment needs further investigation.

68Ga-DOTANOC Focal Pulmonary Activity With No Corresponding CT Abnormality.

A 28-year-old woman with medullary thyroid cancer treated with total thyroidectomy and bilateral central and right lateral neck nodal resection postoperatively had increasing calcitonin and carcinoembryonic antigen values. A Ga-DOTANOC PET/CT study performed showed tracer-avid disease in the neck, mediastinal, and hilar lymph nodes. However, there were 3 tracer-avid foci in the lungs bilaterally, suggestive of lung metastases but with no corresponding abnormalities on low-dose CT. A negative contrast-enhanced CT of the lungs along with clinical and radiological follow-up confirmed that the lung activity was artifactual, demonstrating the possibility of Ga-DOTANOC-avid iatrogenic pulmonary microembolism.

Effectiveness and side-effects of peptide receptor radionuclide therapy for neuroendocrine neoplasms in Germany: A multi-institutional registry study with prospective follow-up.

BACKGROUND: Monocentric and retrospective studies indicate effectiveness of peptide receptor radionuclide therapy targeting somatostatin receptors of neuroendocrine neoplasms. We assessed overall and progression-free survival and adverse events of peptide receptor radionuclide therapy by a multi-institutional, board certified registry with prospective follow-up in five centres in Germany. METHODS: A total of 450 patients were included and followed for a mean of 24.4 months. Most patients had progressive low- or intermediate grade neuroendocrine neoplasms and 73% were pretreated with at least one therapy. Primary neuroendocrine neoplasms were mainly derived of pancreas (38%), small bowel (30%), unknown primary (19%) or bronchial system (4%). Patients were treated with Lutetium-177 in 54%, with Yttrium-90 in 17% and with both radionuclides in 29%. Overall and progression-free survival was determined with Kaplan-Meier curves and uni-variate log rank test Cox models. FINDINGS: Median overall survival of all patients was 59 (95% confidence interval [CI] 49-68.9) months. Overall survival was significantly inferior in the patients treated with Yttrium-90 solely (hazard ratio, 3.22; 95% CI, 1.83-5.64) compared to any peptide receptor radionuclide therapy with Lutetium-177. Grade II (hazard ratio, 2.06; 95% CI, 0.79-5.32) and grade III (hazard ratio, 4.22; 95% CI, 1.41-12.06) neuroendocrine neoplasms had significantly worse overall survival than grade I neuroendocrine neoplasms. Patients with small neuroendocrine neoplasms of small bowel had significantly increased survival (hazard ratio, 0.39; 95% CI, 0.18-0.87) compared to neuroendocrine neoplasms of other locations. Median progression-free survival was 41 (35.9-46.1) months and significantly inferior in patients treated with Yttrium solely (hazard ratio, 2.7; 95% CI, 1.71-4.55). Complete remission was observed in 5.6% of patients, 22.4% had a partial remission, 47.3% were stable and 4% were progressive as best response. Adverse events of bone marrow and kidney function higher than grade III occurred in 0.2-1.5% of patients. INTERPRETATION: These results indicate that peptide receptor radionuclide therapy is a highly effective therapy for patients with low to intermediate grade neuroendocrine neoplasms with minor adverse events.

Preliminary experience with (68)Ga-DOTA-lanreotide positron emission tomography.

AIM: Positron emission tomography (PET) of (68)Ga-radiolabelled (SST) somatostatin receptor (R) binding peptides has recently been evaluated in SSTR positive tumor patients. First promising results in lung and thyroid tumor patients with (111)In-DOTA-Lanreotide (DOTA-LAN) scintigraphy have been described. We report our first experience with (68)Ga-labeled DOTA-LAN. METHODS: Eleven patients (3 non small cell lung cancer [NSCLC], 3 small cell lung cancer [SCLC], 3 radioiodine negative thyroid cancer, 2 medullary thyroid cancer [MTC]) were investigated. After intravenous injection of 75-150 MBq (68)Ga-DOTA-LAN dynamic studies were acquired over the tumor site for the first 40 min with a dedicated PET scanner in 3 patients, and 2 partial body scans were acquired at 20 and 50 min p.i. in 2 patients. Whole body acquisitions at 90 min after injection were acquired in all 11 patients. Image reconstruction was performed by iterative reconstruction utilizing additional transmission scans for attenuation correction. Vital parameters were recorded during the PET study and up to 24 h p.i. Blood and urinary sampling was done up to 4 hr after tracer injection in 8 patients. PET results were compared to conventional imaging techniques (CIT), i.e. computed tomography (CT) and/or magnetic resonance imaging (MRI). In 5 patients, (68)Ga-DOTA-LAN was compared with 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)F-FDG). RESULTS: After intravenous (i.v.) injection of (68)Ga-DOTA-LAN the radioactivity in the blood rapidly decreased to less then 20% of the injected dose (ID) within the first 20 min and further decreased to less than 9% ID after 4 h. A cumulative urinary excretion of (68)Ga-DOTA-LAN up to 29.2 + or - 13.2% ID at 4 h was found. No acute side effects were observed. Tumor sites were visualized already during the first min after injection. Comparison of positron emission tomography (PET) and CIT showed concordant results in 3/8 patients and partial concordant results in 5/8 patients with matched results for the primary/recurrent tumor, mediastinal lymph nodes, or adrenal gland metastases. Partial concordant results were seen for the lung, bone, liver and cervical lymph node metastases. Micronodular metastases of the lung and the cerebrum were not visualized by (68)Ga-DOTA-LAN PET. The maximal standardized uptake values of the lung and bone tumor lesions ranged from 6 to 8 g/ml at 90 min p.i.. CONCLUSIONS: (68)Ga-DOTA-LAN visualized the majority of tumor lesions. Further studies are required to assess the clinical value, and to obtain the best imaging protocol of this new PET SSTR tracer.

High-dose gallium-67 therapy in patients with relapsed acute leukaemia: a feasibility study.

Gallium-67 (67Ga) accumulates in malignant tissues via the transferrin receptor without need for a monoclonal antibody and emits cytotoxic low-energy electrons. In this study we investigated the feasibility, pharmacokinetics, toxicity and preliminary efficiency of high-dose 67Ga injected intravenously (i.v.) in patients with acute leukaemia not responding to conventional therapy. Twelve doses of 36-105 mCi of Gallium67 citrate were administered as a push injection to eight patients with resistant leukaemia in a pilot study. All five patients with acute myeloid leukaemia (AML) and three patients with acute lymphoblastic leukaemia (ALL) had resistant disease or resistant relapse. No (sub)acute toxicity was observed. Independent of the administered dose, whole-blood radioactivity levels 10 min after administration measured only 1.25 +/- 1.39 microCi ml-1, indicating a large volume of distribution. Urine excretion in the first 24 h ranged from 18% to 51.5% (median 29.5%) of the administered dose. Cellular uptake of 67Ga was less than in previous in vitro studies. Whole-body radiation dose was estimated to be 0.25 +/- 0.03 cGy mCi-1. Red marrow dose was estimated to be between 0.18 +/- 0.02 and 0.97 +/- 0.12 cGy mCi-1. One definite response was observed in an ALL patient with disappearance of skin lesions, normalisation of the enlarged spleen and profound leucopenia. Three other patients showed transient reductions in white blood cell counts without disappearance of blasts from the peripheral blood. We conclude that high-dose i.v. 67Ga can be safely administered but that the uptake of 67Ga in blast cells must increase to make 67Ga therapeutically useful in patients with relapsed leukaemia.

Severe hypersensitivity reaction to injectable Gallium 67 in a worker exposed to silica.

Gallium 67 scintigraphy is employed in the evaluation of workers with possible pneumoconiosis. To our knowledge, however, a severe hypersensitivity reaction following the intravenous injection of Gallium 67 has not been described. We report the case of a worker chronically exposed to silica who developed an allergic cutaneous and severe articular reaction following the injection of Gallium 67 while being investigated for possible silicosis. Hilar adenopathy was noted on the chest roentgenogram and, retrospectively, circulating immune complexes were found in the patient's serum. The presence of a positive prick skin test to benzyl alcohol suggests that this preservative caused the hypersensitivity reaction.

Survival of rabbit platelets labeled with gallium 67.

The viability of rabbit platelets labeled with radioactive gallium was determined to analyze the feasibility of using platelets labeled with gallium 68 as an imaging reagent for positron emission tomography. Platelets were labeled with a complex of the longer lived gallium 67 and mercaptopyridine-N-oxide (MPO) or with sodium chromate Cr 51. Their survival after transfusion was measured. Labelling efficiency of 67Ga-MPO was 6.5% to 45.8% (26.8% +/- 2.8%) when platelets were suspended in saline solution, but was much lower (1.6% +/- 0.8%) in plasma. Platelets labeled with either radioisotope in a saline medium survived as well as platelets labeled with 51Cr in plasma. Recovery values 1 hour after transfusion and mean platelet survivals were 68.6% +/- 4.9% and 3.4 +/- 0.2 days for 67Ga in saline solution, 76.5% +/- 6.8% and 3.8 +/- 0.5 days for 51Cr in saline solution, and 73.7% +/- 7.4% and 3.6 +/- 0.5 days for 51Cr in plasma. Labeled platelet concentrates always contained extra radioactivity not firmly bound to viable platelets. A postlabeling wash in saline solution did not reduce this contamination and resulted in reduction of the number of viable platelets. The results showed that rabbit platelets labeled with 67Ga-MPO survived in the circulation as well as those labeled by a standard protocol with sodium chromate Cr 51.

Effects of radiopharmaceuticals on radioenzymatic assays of aminoglycoside antibiotics: interference by gallium-67 and its elimination.

Radionuclides currently used in clinical medicine were evaluated for their possible interference with radioenzymatic assays of aminoglycoside antibiotics. Of the radiopharmaceuticals tested, only (67)Ga citrate interfered with the radioenzymatic assay of gentamicin. Radioenzymatic assay of serum samples obtained from patients receiving (67)Ga yielded gentamicin concentrations falsely elevated by more than 1 mug/ml for approximately 1 week after (67)Ga administration. A procedure was developed to eliminate (67)Ga interference with radioenzymatic assays of aminoglycoside antibiotics. After (67)Ga citrate was spotted onto phosphocellulose filter disks, the filters were immersed in 7.2 N HCl, and radioactivity was removed by successive extractions of the acid phase with diisopropyl ether. After three extractions, less than 0.1% of the original radioactivity remained. Similar extraction of disks containing (14)C-adenylylated gentamicin or tobramycin or (14)C-acetylated amikacin had no effect on (14)C radioactivity. The concentrations of aminoglycosides in serum standards supplemented with (67)Ga citrate were determined accurately by radioenzymatic assays followed by extraction with diisopropyl ether. Concentrations of gentamicin in six serum samples from patients injected with (67)Ga during gentamicin therapy, as determined by radioenzymatic assay and extraction, were within 9% of the results obtained by reassay of the same samples after the decay of (67)Ga.

Error in anti-DNA antibody radioimmunoassay after gallium scanning.

Significant interference with the accurate measurement of anti-DNA antibodies occurs after gallium-67 scanning. The observed effect is dependent on the radioimmunoassay used. False-negative results are observed with a modified Farr assay whereas false-positive results are noted in the millipore filter assay. These spurious values are the result of persistent radioactivity in the patients' sera after administration of 67Ga citrate.