Reducing Radiation Exposure from PET Patients.

This study measured the typical emitted radiation rate from the urinary bladder of PET patients after their scan and investigated simple methods for reducing the emitted radiation before discharge. Methods: The study included 83 patients (63 18F-FDG and 20 18F-NaF patients). Emitted radiation from the patients' urinary bladder was measured with an ionization survey meter at a 1-m distance, presuming the urinary bladder to be the primary source of radiation. The measurements were taken at different time points after PET image acquisition: immediate (prevoid 1), voided (postvoid 1), after waiting 30 min in the uptake room while drinking 500 mL of water (prevoid 2), and voided again (postvoid 2). Results: For 18F-FDG patients, the reduction of emitted radiation due to drinking water and voiding alone from prevoid 1 to decay-corrected postvoid 2 was an average of 22.49% ± 7.48% (13.65 ± 3.42 µSv/h to 10.48 ± 2.37 µSv/h, P < 0.001). For 18F-NaF patients, the reduction was an average of 25.80% ± 10.03% (9.83 ± 2.01 µSv/h to 7.23 ± 1.49 µSv/h, P < 0.001). Conclusion: In addition to the physical decay of the radiotracers, using the biologic clearance properties resulted in a significant decrease of the emitted radiation in this study. Implementing additional water consumption to facilitate voiding with 30 min of wait time before discharging certain 18F-FDG and 18F-NaF patients who need to be in close contact with others, such as elderly, caregivers, and inpatients, might facilitate lowering their emitted radiation by an average of 22%-25% due to voiding, not counting in the physical decay that should add an additional 17% reduction.

Effect of brown adipose tissue activation on myocardial fluorine-18-fluorodeoxyglucose uptake.

The aim of this study is to investigate the relationship between brown adipose tissue (BAT) activation and myocardial fluorine-18-fluorodeoxyglucose ([18F] FDG) uptake in terms of intensity and patterns. The patients were divided into two groups as follows: BAT and control groups. The BAT group consists of 34 cases that showed BAT uptake. The control group, with no BAT uptake, included 68 patients who were matched for body mass index, gender, and season. The scans were retrospectively reviewed by two nuclear medicine physicians who visually evaluated the intensity of myocardial [18F] FDG uptake. The myocardial [18F] FDG uptake was visually classified into the following three patterns: diffuse, heterogeneous, and focal. The regions of activated BAT distribution were noted. The mean myocardial [18F] FDG uptake was 2.50 ± 0.75 for the BAT group and 2.13 ± 0.88 for the control group with a statistically significant difference (P = 0.031). The myocardial [18F] FDG uptake pattern was similar in the BAT and control groups with the diffuse pattern being the most common, followed by the heterogeneous and less commonly focal. In the BAT group, the anatomical distribution of BAT was mainly in supraclavicular, paravertebral, and axillary and to a lesser extent in cervical regions. BAT group had a significantly higher intensity of [18F] FDG myocardial uptake compared to that of the control group. The presence of activated BAT did not affect the pattern of myocardial uptake. Knowledge of these findings may help in understanding the variability of myocardial [18F] FDG uptake and consequently in avoiding misinterpretation of cardiac findings in positron-emission tomography/computed tomography studies.

The efficacy of the available peptide receptor radionuclide therapy for neuroendocrine tumors: a meta-analysis.

AIM: This study was carried out to compare the efficacy of Y, Lu, and combination of both radiotracers (tandem) peptide receptor radionuclide therapy (PRRT) in patients with inoperable and metastatic neuroendocrine tumors. MATERIALS AND METHODS: Systematic searches of PubMed and SciVerse Scopus databases were performed till December of 2016. The data were categorized into three groups: Y-PRRT, Lu-PRRT, and tandem-PRRT. Each group was subdivided on the basis of the response criteria used: Response Evaluation Criteria in Solid Tumors (RECIST) or Southwest Oncology Group (SWOG) criteria. Disease response and disease control rates of each group were analyzed. RESULTS: For the RECIST group, Y-PRRT disease response rates ranged from 22.81 to 56.1%, with a pooled random effect of 42.92%, and the disease control rate was 100%. Lu-PRRT disease response rates ranged from 27.63 to 57.35%, with a pooled random effect of 33.41%, and disease control rates ranged between 71.88 and 100%, with a pooled fixed effect of 79.32%. As for tandem-PRRT, disease response rates ranged between 42.11 and 66.67%, with a pooled fixed effect of 50.52%, and the disease control rate ranged between 93.33 and 100%, with a pooled fixed effect of 98.97%.For the SWOG group, Y-PRRT disease response rates ranged from 5.13 to 26.56%, with a pooled random effect of 13.4%, and disease control rates ranged between 76.56 and 85.9%, with a pooled fixed effect of 80.93%. Lu-PRRT disease response rates ranged from 6.06 to 60.29%, with a pooled random effect of 26.4%, and the disease control rates between 48.48 and 85.29%, with a pooled random effect of 74.53%. CONCLUSION: Y-PRRT had the highest disease control rates under both RECIST and SWOG criteria. Tandem-PRRT had the highest disease response rate in the RECIST criteria, indicating that PRRT should be customized to each patient individually for maximum benefit.

Ultrastructure of Hyperfunctioning Parathyroid Glands: Does it Explain Various Patterns of 99mTc-sestamibi Uptake.

The aim of this study was to correlate the uptake of 99mTc-methoxy-isobutyl-isonitrile (MIBI) with ultra-structural features of parathyroid adenomas. Twenty patients with proven primary hyperparathyroidism were evaluated prospectively. Preoperative double-phase 99mTc-MIBI scintigraphy was performed in all patients and the degree of tracer uptake by the parathyroid lesions was assessed visually and semi-quantitatively. The excised glands were examined histologically and ultrastructurally, and their features were correlated with the degree of the radiotracer uptake. At surgery, 21 parathyroid adenomas were removed (double adenoma in one patient and a solitary adenoma in each of the remaining 19 patients). 99mTc-MIBI scan detected 18 of the 21 adenomas. There was positive correlation between the degree of 99mTc-MIBI uptake and the mitochondrial contents of the parathyroid adenoma cells. Four adenomas with intense uptake had high content of mitochondria in the cells. The three false-negative scans had low-to-moderate mitochondrial content. 99mTc-MIBI uptake is related to the mitochondrial content of the parathyroid adenoma cells.

Tumor dosimetry using [124I]m-iodobenzylguanidine microPET/CT for [131I]m-iodobenzylguanidine treatment of neuroblastoma in a murine xenograft model.

PURPOSE: [(124)I]m-iodobenzylguanidine ((124)I-mIBG) provides a quantitative tool for pretherapy tumor imaging and dosimetry when performed before [(131)I]m-iodobenzylguanidine ((131)I-mIBG) targeted radionuclide therapy of neuroblastoma. (124)I (T (1/2) = 4.2 days) has a comparable half-life to that of (131)I (T (1/2) = 8.02 days) and can be imaged by positron emission tomography (PET) for accurate quantification of the radiotracer distribution. We estimated expected radiation dose in tumors from (131)I-mIBG therapy using (124)I-mIBG microPET/CT imaging data in a murine xenograft model of neuroblastoma transduced to express high levels of the human norepinephrine transporter (hNET). PROCEDURES: In order to enhance mIBG uptake for in vivo imaging and therapy, NB 1691-luciferase (NB1691) human neuroblastoma cells were engineered to express high levels of hNET protein by lentiviral transduction (NB1691-hNET). Both NB1691 and NB1691-hNET cells were implanted subcutaneously and into renal capsules in athymic mice. (124)I-mIBG (4.2-6.5 MBq) was administered intravenously for microPET/CT imaging at 5 time points over 95 h (0.5, 3-5, 24, 48, and 93-95 h median time points). In vivo biodistribution data in normal organs, tumors, and whole-body were collected from reconstructed PET images corrected for photon attenuation using the CT-based attenuation map. Organ and tumor dosimetry were determined for (124)I-mIBG. Dose estimates for (131)I-mIBG were made, assuming the same in vivo biodistribution as (124)I-mIBG. RESULTS: All NB1691-hNET tumors had significant uptake and retention of (124)I-mIBG, whereas unmodified NB1691 tumors did not demonstrate quantifiable mIBG uptake in vivo, despite in vitro uptake. (124)I-mIBG with microPET/CT provided an accurate three-dimensional tool for estimating the radiation dose that would be delivered with (131)I-mIBG therapy. For example, in our model system, we estimated that the administration of (131)I-mIBG in the range of 52.8-206 MBq would deliver 20 Gy to tumors. CONCLUSIONS: The overexpression of hNET was found to be critical for (124)I-mIBG uptake and retention in vivo. The quantitative (124)I-mIBG PET/CT is a promising new tool to predict tumor radiation doses with (131)I-mIBG therapy of neuroblastoma. This methodology may be applied to tumor dosimetry of (131)I-mIBG therapy in human subjects using (124)I-mIBG pretherapy PET/CT data.

Labeling, stability and biodistribution studies of 99mTc-cyclized Tyr3-octreotate derivatives.

INTRODUCTION: To probe the interplay between radiotracer stability and somatostatin receptor affinity, Tyr(3)-octreotate and six variations of its peptide sequence, for which the Re-cyclized products were previously reported, were radiolabeled with (99m)Tc and investigated for their in vitro stability. METHODS: Radiolabeling of the peptides was effected by ligand exchange from (99m)Tc-glucoheptonate, and the desired products were purified by radio-RP-HPLC. The in vitro stability in phosphate buffered saline, mouse serum and cysteine solutions at physiological temperature and pH for all seven (99m)Tc-cyclized peptides was determined by radio-RP-HPLC and radio-TLC. Normal CF-1 mouse biodistribution studies were performed for three of the (99m)Tc-cyclized peptides. RESULTS: Based on the fully characterized Re-cyclized peptide analogues, four (99m)Tc-coordination motifs were proposed for the (99m)Tc-cyclized peptides. Technetium-99m-cyclized Tyr(3)-octreotate derivatives with N(2)S(2) metal coordination modes and large metal ring sizes were susceptible to oxidation and loss of (99m)Tc in the form of (99m)TcO(4)(-), as evidenced by their instability in the various solutions under physiological conditions (15-58% intact at 24 h). As anticipated, the addition of a third cysteine to the sequence stabilized the (99m)Tc metal coordination, and peptides with NS(3) coordination modes remained >85% intact out to 24 h. No significant differences were observed in the biodistribution studies performed with three peptides of varying stabilities. CONCLUSIONS: Improvements in stability were not sufficient to outweigh the low somatostatin receptor affinity for the peptides in this study. Further improvements in the peptide sequence and/or metal coordination are needed to result in a radiodiagnostic/radiotherapeutic pair for targeting the somatostatin receptor.

Radiation dose estimation using preclinical imaging with 124I-metaiodobenzylguanidine (MIBG) PET.

PURPOSE: A pretherapy 124I-metaiodobenzylguanidine (MIBG) positron emission tomography (PET)/computed tomography (CT) provides a potential method to estimate radiation dose to normal organs, as well as tumors prior to 131I-MIBG treatment of neuroblastoma or pheochromocytoma. The aim of this work was to estimate human-equivalent internal radiation dose of 124I-MIBG using PET/CT data in a murine xenograft model. METHODS: Athymic mice subcutaneously implanted with NB1691 cells that express high levels of human norepinephrine transporter (n = 4) were imaged using small animal microPET/CT over 96 h (approximate imaging time points: 0.5, 2, 24, 52, and 96 h) after intravenous administration of 3.07-4.84 MBq of 124I-MIBG via tail vein. The tumors did not accumulate 124I-MIBG to a detectable level. All four animals were considered as control and organ radiation dosimetry was performed. Volumes of interest were drawn on the coregistered CT images for thyroid, heart, lung, liver, kidney, and bladder, and transferred to PET images to obtain pharmacokinetic data. Based on tabulated organ mass distributions for both mice and adult male human, preclinical pharmacokinetic data were extrapolated to their human-equivalent values. Radiation dose estimations for different age groups were performed using the OLINDA/EXM software with modified tissue weighting factors in the recent International Commission on Radiological Protection (ICRP) Publication 103. RESULTS: The mean effective dose from 124I-MIBG using weighting factors from ICRP 103 to the adult male was estimated at 0.25 mSv/MBq. In different age groups, effective doses using values from ICRP 103 were estimated as follows: Adult female: 0.34, 15-yr-old: 0.39 mSv/MBq, 10-yr-old: 0.58 mSv/MBq, 5-yr-old: 1.03 mSv/MBq, 1-yr-old: 1.92 mSv/MBq, and newborn: 3.75 mSv/ MBq. For comparison, the reported effective dose equivalent of 124I-NaI for adult male (25% thyroid uptake, MIRD Dose Estimate Report No. 5) was 6.5 mSv/MBq. CONCLUSIONS: The authors estimated human-equivalent internal radiation dose of 124I-MIBG using preclinical imaging data. As a reference, the effective dose estimation showed that 124I-MIBG would deliver less radiation dose than 124I-NaI, a radiotracer already being used in patients with thyroid cancer.

In vitro structure-activity relationship of Re-cyclized octreotide analogues.

INTRODUCTION: Development of radiolabeled octreotide analogues is of interest for targeting somatostatin receptor (SSTR)-positive tumors for diagnostic and therapeutic purposes. We are investigating a direct labeling approach for incorporation of a Re ion into octreotide analogues, where the peptide sequences are cyclized via coordination to Re rather than through a disulfide bridge. METHODS: Various octreotide analogue sequences and coordination systems (e.g., S(2)N(2) and S(3)N) were synthesized and cyclized with nonradioactive Re. In vitro competitive binding assays with (111)In-DOTA-Tyr(3)-octreotide in AR42J rat pancreatic tumor cells yielded IC(50) values as a measure of SSTR affinity of the Re-cyclized analogues. Three-dimensional structures of Re-cyclized Tyr(3)-octreotate and its disulfide-bridged analogue were calculated from two-dimensional NMR experiments to visualize the effect of metal cyclization on the analogue's pharmacophore. RESULTS: Only two of the 11 Re-cyclized analogues investigated showed moderate in vitro binding affinity toward somatostatin subtype 2 receptors. Three-dimensional molecular structures of Re- and disulfide-cyclized Tyr(3)-octreotate were calculated, and both of their pharmacophore turns appear to be very similar with minor differences due to metal coordination to the amide nitrogen of one of the pharmacophore amino acids. CONCLUSIONS: Various Re-cyclized analogues were developed and analogue 4 had moderate affinity toward somatostatin subtype 2 receptors. In vitro stable studies that are in progress showed stable radiometal cyclization of octreotide analogues via NS(3) and N(2)S(2) coordination forming five- and six-membered chelate rings. In vivo biodistribution studies are underway of (99m)Tc-cyclized analogue 4.