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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 -
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 -
Stomatologija 2007The aim of this study was to evaluate the effect of cyclic 3', 5' adenosin-monophosphate (cAMP) on DNA synthesis of embryonic alveolar bone in tissue culture.
UNLABELLED
The aim of this study was to evaluate the effect of cyclic 3', 5' adenosin-monophosphate (cAMP) on DNA synthesis of embryonic alveolar bone in tissue culture.
MATERIAL AND METHODS
Bone fragments were cultured in the medium composed of 80% medium 199, 15% horse serum, 4 mg/ml glucose, 100 microg/ml penicillin using the grid method. The explants were cultured up to 12 days. In the second series, the effect of cAMP in a concentration of 10(-6)M on bone during 12 days was studied. DNA synthesis was determined by calculating mitotic labelling indices for (3)H-thymidine incorporation into cells within cultured explants at 3 to 12 days. The medium was supplemented with 1 microCurie/ml (3)H-thymidine for 4 hours and processed for autoradiography. The mitotic labelling index was determined in the histological sections. All values wer presented as mean+/-standard deviation. Statistical significance was defined by p-values of 0.05 or less.
RESULTS
Morphological and statistical analysis showed that there were differences in mitotic incidence (MI) and silver grain densities over osteoblasts in control cultures and with cAMP. The mean value of MI was 4,627+/-1,001 in control and 7,706+/-1,188 in the cultures where cAMP was added (p<0.05).
CONCLUSION
Thus cAMP inhibited bone resorption and stimulated new bone formation in tissue culture. This study provides a novel concept that may help to identify new therapeutic targets.
Topics: Alveolar Process; Animals; Autoradiography; Bone Matrix; Bone Resorption; Calcification, Physiologic; Cell Count; Cell Proliferation; Culture Media; Cyclic AMP; DNA; Mice; Mitotic Index; Osteoblasts; Osteogenesis; Radiopharmaceuticals; Thymidine; Tissue Culture Techniques; Tritium
PubMed: 18303273
DOI: No ID Found -
World Journal of Surgical Oncology Apr 2007Intraoperative localization of image or endoscopy-detected lesions occasionally pose surgical challenges due to the small lesion size and/or difficult anatomic exposure....
BACKGROUND
Intraoperative localization of image or endoscopy-detected lesions occasionally pose surgical challenges due to the small lesion size and/or difficult anatomic exposure. Identification of such lesions can be facilitated using a hand-held gamma probe with utilization of Tc-99m macroaggregate albumen (MAA) localization technique. The radiopharmaceutical injection can be performed using ultrasound (US) or endoscopy guidance.
CASE PRESENTATIONS
The clinical use of the Tc-99m MAA protocol gamma probe-guided surgery was discussed in three representative cases. Surgical indication was diagnostic exploration in two patients with suspicious lymphadenopathy, and determination of extent of surgical resection in a patient with polyposis. Lesion localization with 100 microcurie (3.7 MBq) Tc-99m MAA prior to surgical exploration resulted in definitive localization of lesions intraoperatively.
CONCLUSION
The use Tc-99m MAA deposition technique at the site of surgical target is a highly efficient radio-guided surgery technique with definitive impact on the success of surgical exploration in selected indications.
Topics: Adult; Aged; Female; Humans; Male; Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Radiosurgery; Technetium Tc 99m Aggregated Albumin
PubMed: 17459152
DOI: 10.1186/1477-7819-5-43 -
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 -
Journal of Nuclear Medicine : Official... May 1994SPECT imaging with 123I-labeled methyl 3 beta-(4-iodophenyl)tropane-2 beta-carboxylate ([123I]beta-CIT) in nonhuman primates has shown brain striatal activity, which...
UNLABELLED
SPECT imaging with 123I-labeled methyl 3 beta-(4-iodophenyl)tropane-2 beta-carboxylate ([123I]beta-CIT) in nonhuman primates has shown brain striatal activity, which primarily reflects binding to the dopamine transporter. The biodistribution and calculated radiation-absorbed doses of [123I]beta-CIT administered to eight healthy subjects were measured with attention to the accurate determination of organ time-activity data.
METHODS
Whole-body transmission images were obtained with a scanning line source for attenuation correction of the emission images. Following administration of 92.5 +/- 22.2 MBq (2.5 +/- 0.6 mCi) of [123I]beta-CIT, subjects were imaged with a whole-body imager every 30 min for 3 hr, every 60 min for the next 3 hr and at 12, 24 and 48 hr postinjection. Regional body conjugate counts were converted to microcuries of activity, with a calibration factor determined in a separate experiment using a distributed source of 123I.
RESULTS
The peak brain uptake represented 14% of the injected dose, with 2% of the activity approximately overlying the striatal region. Highest radiation-absorbed doses were to the lung (0.1 mGy/MBq, 0.38 rads/mCi), liver (0.087 mGy/MBq, 0.32 rads/mCi) and lower large intestine (0.053 mGy/MBq, 0.20 rads/mCi).
CONCLUSIONS
Iodine-123-beta-CIT is a promising SPECT agent for imaging of the dopamine transporter in humans with favorable dosimetry and high brain uptake.
Topics: Adult; Brain; Cocaine; Female; Humans; Iodine Radioisotopes; Male; Radiation Dosage; Tissue Distribution; Tomography, Emission-Computed, Single-Photon
PubMed: 8176456
DOI: No ID Found -
Journal of Nuclear Medicine : Official... Jul 1991A noninvasive, scintigraphic technique for quantifying large intestinal transit time that provides low radiation doses was developed. The scintigraphic large intestinal...
A noninvasive, scintigraphic technique for quantifying large intestinal transit time that provides low radiation doses was developed. The scintigraphic large intestinal transit (SLIT) method uses a total of 100 microCi of 111In encapsulated in ten 2-cm nondigestible capsules, which are ingested after a 6-hr fast. Two hundred fifty microcuries of 99mTc-sulfur colloid were given to outline the gastrointestinal tract. Images were acquired at 4-hr intervals until all capsules were excreted. Normal volunteers (n = 10) consumed a standardized diet 2 days prior and during imaging. Segmental transit times were measured in the following: ascending, transverse, descending, recto-sigmoid colons; hepatic and splenic flexures. The radiation absorbed dose to the large intestine for the SLIT technique is less than half of that associated with other radiographic methods of colonic transit time measurement.
Topics: Adult; Capsules; Colon; Gastrointestinal Transit; Humans; Indium Radioisotopes; Pentetic Acid; Radionuclide Imaging
PubMed: 2066794
DOI: No ID Found -
Plant Physiology Feb 1989The pedicel of tomato fruit (Lycopersicon esculentum Mill., cv ;Rutgers') of different developmental stages from immature-green (IG) to red was injected on the vine with...
The pedicel of tomato fruit (Lycopersicon esculentum Mill., cv ;Rutgers') of different developmental stages from immature-green (IG) to red was injected on the vine with 7 microcuries [(14)C(U)]sucrose and harvested after 18 hours. Cell walls were isolated from outer pericarp and further fractionated yielding ionically associated pectin, covalently bound pectin, hemicellulosic fraction I, hemicellulosic fraction II, and cellulosic fraction II. The dry weight of the total cell wall and of each cell wall fraction per gram fresh weight of pericarp tissue decreased after the mature-green (MG) stage of development. Incorporation of radiolabeled sugars into each fraction decreased from the IG to MG3 (locules jellied but still green) stage. Incorporation in all fractions increased from MG3 to breaker and turning (T) and then decreased from T to red. Data indicate that cell wall synthesis continues throughout ripening and increases transiently from MG4 (locules jellied and yellow to pink in color) to T, corresponding to the peak in respiration and ethylene synthesis during the climacteric. Synthesis continued at a time when total cell wall fraction dry weight decreased indicating the occurrence of cell wall turnover. Synthesis and insertion of a modified polymer with removal of other polymers may produce a less rigid cell wall and allow softening of the tissue integrity during ripening.
PubMed: 16666568
DOI: 10.1104/pp.89.2.477