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European Journal of Nuclear Medicine... Aug 2023To introduce a biomarker-based dosimetry method for the rational selection of a treatment activity for patients undergoing radioactive iodine I therapy (RAI) for...
The use of single-timepoint images to link administered radioiodine activity (MBq) to a prescribed lesion radiation-absorbed dose (cGy): a regression-based prediction interval tool for the management of well-differentiated thyroid cancer patients.
PURPOSE
To introduce a biomarker-based dosimetry method for the rational selection of a treatment activity for patients undergoing radioactive iodine I therapy (RAI) for metastatic differentiated thyroid cancer (mDTC) based on single-timepoint imaging of individual lesion uptake by I PET.
METHODS
Patients referred for RAI therapy of mDTC were enrolled in institutionally approved protocols. A total of 208 mDTC lesions (in 21 patients) with SUV > 1 underwent quantitative PET scans at 24, 48, 72, and 120 h post-administration of 222 MBq of theranostic NaI-I to determine the individual lesion radiation-absorbed dose. Using a general estimating equation, a prediction curve for biomarker development was generated in the form of a best-fit regression line and 95% prediction interval, correlating individual predicted lesion radiation dose metrics, with candidate biomarkers ("predictors") such as SUV and activity in microcurie per gram, from a single imaging timepoint.
RESULTS
In the 169 lesions (in 15 patients) that received I therapy, individual lesion cGy varied over 3 logs with a median of 22,000 cGy, confirming wide heterogeneity of lesion radiation dose. Initial findings from the prediction curve on all 208 lesions confirmed that a 48-h SUV was the best predictor of lesion radiation dose and permitted calculation of the I activity required to achieve a lesional threshold radiation dose (2000 cGy) within defined confidence intervals.
CONCLUSIONS
Based on MIRD lesion-absorbed dose estimates and regression statistics, we report on the feasibility of a new single-timepoint I-PET-based dosimetry biomarker for RAI in patients with mDTC. The approach provides clinicians with a tool to select personalized (precision) therapeutic administration of radioactivity (MBq) to achieve a desired target lesion-absorbed dose (cGy) for selected index lesions based on a single 48-h measurement I-PET image, provided the selected activity does not exceed the maximum tolerated activity (MTA) of < 2 Gy to blood, as is standard of care at Memorial Sloan Kettering Cancer Center.
TRIAL REGISTRATION
NCT04462471, Registered July 8, 2020. NCT03647358, Registered Aug 27, 2018.
Topics: Humans; Adenocarcinoma; Iodine Radioisotopes; Radiation Dosage; Thyroid Neoplasms
PubMed: 37171634
DOI: 10.1007/s00259-023-06240-1 -
Frontiers in Bioengineering and... 2019To investigate the therapeutic efficacy of intratumoral injection of I-AA98 mAb for hepatocellular carcinoma (HCC) and its therapy efficacy assessment by...
To investigate the therapeutic efficacy of intratumoral injection of I-AA98 mAb for hepatocellular carcinoma (HCC) and its therapy efficacy assessment by Tc-HYNIC-duramycin and Tc-HYNIC-3PRGD2 SPECT/CT imaging. HCC xenograft tumor mice models were injected intratumorally with a single dose of normal saline, 10 microcurie (μCi) I-AA98 mAb, free I, AA98 mAb, 80 μCi I-AA98 mAb, and 200 μCi I-AA98 mAb. Tc-HYNIC-duramycin and Tc-HYNIC-3PRGD2 micro-SPECT/CT imaging were performed on days 3 and 7, respectively. The T/M ratio for each imaging was compared with the corresponding immunohistochemical staining at each time point. The relative tumor inhibition rates were documented. In terms of apoptosis, the 200 μCi group demonstrated the highest apoptotic index (11.8 ± 3.8%), and its T/M ratio achieved by Tc-HYNIC-duramycin imaging on day 3 was higher than that of the normal saline group, 80 μCi group, 10 μCi group and free I group on day 3, respectively (all < 0.05). On day 3, there was a markedly positive correlation between T/M ratio from Tc-HYNIC-duramycin imaging and apoptotic index by TUNEL staining ( = 0.6981; < 0.05). Moreover, the 200 μCi group showed the lowest T/M ratio on Tc-HYNIC-3PRGD2 imaging (1.0 ± 0.5) on day 7 (all < 0.05) comparing to other groups. The T/M ratio on day 7 was not correlated with integrin αβ staining ( > 0.05). The relative inhibitory rates of tumor on day 14 in the AA98 mAb, 10 μCi, 80 μCi, free I, and 200 μCi groups were 26.3, 55.3, 60.5, 66.3, and 69.5%, respectively. I-AA98 mAb showed more effective apoptosis induced ability for CD146 high expression Hep G2 HCC cells and hold the potential for HCC treatment. Moreover, Tc-HYNIC-Duramycin (apoptosis-targeted) imaging and Tc-HYNIC-3PRGD2 (angiogenesis-targeted) imaging are reliable non-invasive methods to evaluate the efficacy of targeted treatment of HCC.
PubMed: 31799244
DOI: 10.3389/fbioe.2019.00319 -
Journal of Research of the National... 1960A convenient procedure is described for the radioassay of both carbon-14 and tritium in water-soluble, nonvolatile compounds by means of a windowless, gas-flow,...
A convenient procedure is described for the radioassay of both carbon-14 and tritium in water-soluble, nonvolatile compounds by means of a windowless, gas-flow, proportional counter. The materials are counted in uniform films of sodium -(carboxymethyl) cellulose that are "infinitely thick" to the radiation of tritium but not to the radiation of carbon-14. Films of uniform thickness are obtained by new techniques which are described in detail. If only carbon-14 is present, its absolute activity can be calculated conveniently by means of an empirically established curve for the counting-efficiency. If both carbon-14 and tritium are present, the films are counted in the proportional counter and are then recounted in the presence of a screen that stops all radiation from tritium but only a portion of that from carbon-14. From a film with a thickness of 0.8 mg/cm, approximately 43 percent of the radiation of carbon-14 is counted. Of this emerging radiation, approximately 50 percent passes through a screen of ¼-mil double-aluminized "Mylar." By use of suitable calibration curves for counting-efficiency, carbon-14 and tritium in the same sample can be calculated from the counts with, and without, the screen. Satisfactory analyses can be made with samples containing less than 0.001 microcurie of carbon-14 and 0.005 microcurie of tritium. The method is suitable for the radioassay of a wide variety of labeled materials.
PubMed: 32196177
DOI: 10.6028/jres.064A.038 -
Annals of Surgery Nov 1973
Topics: Adrenalectomy; Breast; Breast Neoplasms; Carbon Radioisotopes; Carcinoma, Intraductal, Noninfiltrating; Castration; Chemical Phenomena; Chemistry; Estradiol; Estrogens; Female; Humans; Hydrocortisone; Middle Aged; Neoplasm Metastasis
PubMed: 4355957
DOI: 10.1097/00000658-197311000-00001 -
JSLS : Journal of the Society of... 2004To test the feasibility of using a newly developed device for laparoscopic lymphatic mapping of the colon by simultaneous and quantitative detection of both tissue...
OBJECTIVE
To test the feasibility of using a newly developed device for laparoscopic lymphatic mapping of the colon by simultaneous and quantitative detection of both tissue coloration and radioactivity.
METHODS
Four pigs were used in this study. In each animal, both blue dye and radioisotope injections were utilized. Lymphatic mapping was performed laparoscopically in the sigmoid mesocolon and in the right mesocolon. A solution containing a mix of 35 microcuries of Technetium Tc-99 sulfur Colloid and 1 mL of a vital blue dye was administered subserosally by percutaneous insertion of a 25 gauge needle under laparoscopic control. The new device for automated sentinel-node detection consists of a gamma-probe coupled with a laser device and can be passed through a regular 10-mm trocar. The device detects simultaneously both radioactivity and quantitative tissue coloration. Nodes showing a radioactivity at least 5 times higher than that of the background or that had a blue colorant concentration were considered our sentinel nodes.
RESULTS
Laparoscopic simultaneous and quantitative detection of sentinel nodes was feasible in all pigs. One or more sentinel nodes were identified by either the blue dye or radioisotopic technique in both the sigmoid and right mesocolon. Quantitative tissue coloration detection led to the recognition of additional nodes that were not apparently colored to the naked eye.
CONCLUSION
Laparoscopic sentinel node detection using a device combining gamma and color detection is feasible in the porcine model. The significance of nodes apparently clear but positive with the quantitative detection technique should be further evaluated.
Topics: Animals; Colectomy; Coloring Agents; Feasibility Studies; Laparoscopy; Models, Animal; Radiopharmaceuticals; Rosaniline Dyes; Sentinel Lymph Node Biopsy; Swine; Technetium Tc 99m Sulfur Colloid
PubMed: 15554278
DOI: No ID Found -
Epilepsia Mar 2002Although conventional surgery is presently used to treat seizures of temporolimbic and neocortical origin, deep-seated lesions are often associated with morbidity....
PURPOSE
Although conventional surgery is presently used to treat seizures of temporolimbic and neocortical origin, deep-seated lesions are often associated with morbidity. Stereotactic radiosurgery is a noninvasive procedure that effectively treats patients with vascular malformations and brain tumors, but its efficacy for epileptogenic foci is limited, especially in children.
METHODS
Between 1995 and 1999, four candidates who had medically uncontrolled seizures and localized seizure foci were selected for stereotactic radiosurgery, with a mean age of 9.75 years at the time of surgery (range, 4-17 years). Seizure foci were identified on the basis of ictal and interictal video-EEG. Magnetic resonance (MR) images were obtained before and after surgery. Ictal single-photon emission computed tomography (SPECT) was performed by using stabilized hexamethyl-propyleneamine oxime (HMPAO; 300 microcuries/kg) with early injection after electrographic ictal onset. The clinical features of the patients are given. All radiosurgical procedures were performed with the gamma knife unit with the Leksell stereotactic frame, stereotactic MRI imaging, and the Gamma Plan workstation. Seizure outcome was scored according to Engel's classification.
RESULTS
Two patients had hypothalamic hamartoma (HH), and two had neocortical epilepsy. At mean follow-up of 39.2 months (range, 26-69 months), two patients were seizure free, one with a HH and one with a suggestive developmental tumor in the insular cortex by MRI findings. The other patient with HH had 90% reduction of seizures. One patient with a widespread seizure focus that involved the motor strip was unimproved. The two patients with HH also exhibited markedly improved neurobehavioral status after surgery. There were no significant complications of radiosurgical therapy.
CONCLUSIONS
Our findings suggest that gamma knife surgery is a potentially valuable treatment modality for children with medically intractable epilepsy due to a well-localized seizure focus that is difficult to excise by conventional techniques or for whom they are deemed unsuitable. More widespread application in childhood epilepsy should be investigated in larger series.
Topics: Adolescent; Child, Preschool; Electroencephalography; Epilepsies, Partial; Female; Hamartoma; Humans; Hypothalamic Diseases; Infant; Magnetic Resonance Imaging; Male; Radiosurgery; Stereotaxic Techniques; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Treatment Outcome
PubMed: 11906515
DOI: 10.1046/j.1528-1157.2002.06501.x -
The Journal of Biophysical and... Aug 1961A technic is described for high resolution intracellular autoradiography in the electron microscope. Cultures of LLC-MK(2) monkey kidney cells were incubated for 72...
A technic is described for high resolution intracellular autoradiography in the electron microscope. Cultures of LLC-MK(2) monkey kidney cells were incubated for 72 hours in a medium containing 0.4 microcurie per ml of thymidine-H(3). After labeling, the cells were fixed with osmium tetroxide and embedded in methacrylate. Ultrathin sections of the labeled tissue were taken up on Formvar-coated and carbon-stabilized electron microscope grids. A 150 to 450 A layer of silver metal was then evaporated onto the tissue. The coated grids were exposed to bromine vapor for 1.5 to 2 minutes under red light, allowed to dry for 1 minute, and then covered with a thin film of 1 per cent aqueous gelatin applied by means of a fine wire loop lowered over the grid supported on a glass peg. For autoradiographic exposure, the grids were stored 50 days in a light-proof container at 4 degrees C with calcium chloride desiccant. Development was carried out for 5 minutes at 20 degrees C in Promicrol (May and Baker, England) diluted 1:1 with water, followed by a 1 minute water wash and fixation for 2.5 minutes in 15 per cent aqueous sodium thiosulphate. After removal of the gelatin by immersion for 16 hours in water at 37 degrees C, the autoradiograms were dried and examined in the electron microscope. Ultrastructural detail was fairly well defined and the cytoplasm of each labeled cell was covered with an electron opaque deposit of silver, suggesting that a polynucleotide containing thymidine may be synthesized in the cytoplasm. The matter is discussed.
PubMed: 19866594
DOI: 10.1083/jcb.10.4.577 -
Plant Physiology Feb 1984This study was conducted to examine protein synthesis and l-[(35)S] methionine incorporation into the endosperm of Zea mays L. kernels developing in vitro. Two-day-old...
This study was conducted to examine protein synthesis and l-[(35)S] methionine incorporation into the endosperm of Zea mays L. kernels developing in vitro. Two-day-old kernels of the inbred line W64A were placed in culture on a defined medium containing 10 microCuries l-[(35)S] methionine per milliliter (13 milliCuries per millimole) and harvested at 10, 15, 20, 25, 30, 35, and 40 days after pollination. Cultured kernels attained a final endosperm mass of 120 milligrams compared to 175 milligrams for field-grown controls. Field and cultured kernels had similar concentrations (microgram per milligram endospern) for total protein, albumin plus globulin, zein, and glutelin fractions at most kernel ages.Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing patterns for endosperm proteins were similar for field and cultured kernels throughout development. By 15 days, over 70% of the l-[(35)S]methionine taken up was present in endosperm proteins. Label incorporation visualized by fluorography generally followed the protein intensity of the stained gels. The high methionine content, low molecular weight zeins (i.e. 15 and 9 kilodaltons) were highly labeled. All of the radioactivity in hydrolyzed zein samples was recovered in the methionine peak indicating minimal conversion to l-[(35)S]cysteine. The procedure described here is suitable for long term culture and labeling experiments in which continued kernel development is required.
PubMed: 16663428
DOI: 10.1104/pp.74.2.389 -
Small (Weinheim An Der Bergstrasse,... Aug 2011Raman imaging offers unsurpassed sensitivity and multiplexing capabilities. However, its limited depth of light penetration makes direct clinical translation...
Raman imaging offers unsurpassed sensitivity and multiplexing capabilities. However, its limited depth of light penetration makes direct clinical translation challenging. Therefore, a more suitable way to harness its attributes in a clinical setting would be to couple Raman spectroscopy with endoscopy. The use of an accessory Raman endoscope in conjunction with topically administered tumor-targeting Raman nanoparticles during a routine colonoscopy could offer a new way to sensitively detect dysplastic lesions while circumventing Raman's limited depth of penetration and avoiding systemic toxicity. In this study, the natural biodistribution of gold surface-enhanced Raman scattering (SERS) nanoparticles is evaluated by radiolabeling them with (64) Cu and imaging their localization over time using micropositron emission tomography (PET). Mice are injected either intravenously (IV) or intrarectally (IR) with approximately 100 microcuries (μCi) (3.7 megabecquerel (MBq)) of (64) Cu-SERS nanoparticles and imaged with microPET at various time points post injection. Quantitative biodistribution data are obtained as % injected dose per gram (%ID g(-1)) from each organ, and the results correlate well with the corresponding microPET images, revealing that IV-injected mice have significantly higher uptake (p < 0.05) in the liver (5 h = 8.96% ID g(-1); 24 h = 8.27% ID g(-1)) than IR-injected mice (5 h = 0.09% ID g(-1); 24 h = 0.08% ID g(-1)). IR-injected mice show localized uptake in the large intestine (5 h = 10.37% ID g(-1); 24 h = 0.42% ID g(-1)) with minimal uptake in other organs. Raman imaging of excised tissues correlate well with biodistribution data. These results suggest that the topical application of SERS nanoparticles in the mouse colon appears to minimize their systemic distribution, thus avoiding potential toxicity and supporting the clinical translation of Raman spectroscopy as an endoscopic imaging tool.
Topics: Animals; Copper Radioisotopes; Endoscopy; Female; Mice; Mice, Nude; Microscopy, Electron, Transmission; Nanoparticles; Positron-Emission Tomography; Spectrum Analysis, Raman
PubMed: 21608124
DOI: 10.1002/smll.201002317 -
Plant Physiology Mar 1988Photosynthetic carbon fixation in guard cells was reexamined in experiments with highly purified guard cell protoplasts from Vicia faba L. irradiated with red light. The...
Photosynthetic carbon fixation in guard cells was reexamined in experiments with highly purified guard cell protoplasts from Vicia faba L. irradiated with red light. The fate of (14)CO(2) (4.8 microcuries of NaHCO(3); final concentration: 100 micromolar) supplied to these preparations was investigated with two-dimensional paper, and thin layer chromatography. Rates of CO(2) fixation were 5- to 8-fold higher in the light than in darkness. Separation of acid-stable products into water-insoluble, neutral, and anionic fractions showed that more radioactivity was incorporated into the neutral fraction in the light than in the dark. In the dark, malate and aspartate comprised 90% of the radiolabel found in the anionic fraction, whereas in the light, radioactivity was also found in 3-phosphoglyceric acid (PGA), sugar monophosphates, sugar diphosphates, and triose phosphates. Phosphorylated compounds contained up to 60% of the label in the light-treated anionic fraction. Phosphatase treatment and rechromatography of labeled sugar diphosphate showed the presence of ribulose, a specific metabolite of the photosynthetic carbon reduction pathway (PCRP). In time-course experiments, labeled PGA was detected within 5 seconds. With time, the percentage of label in PGA decreased and that in sugar monophosphate increased. We conclude that PGA is a primary carboxylation product of the PCRP in guard cells and that the activity of the PCRP, and phosphoenolpyruvate-carboxylase is metabolically regulated.
PubMed: 16665973
DOI: 10.1104/pp.86.3.700