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Clinical Ophthalmology (Auckland, N.Z.) 2014Radioactive iodine 131 ((131)I) therapy has long been used in the treatment of differentiated thyroid cancers (DTC). While salivary and lacrimal glandular complications...
BACKGROUND
Radioactive iodine 131 ((131)I) therapy has long been used in the treatment of differentiated thyroid cancers (DTC). While salivary and lacrimal glandular complications secondary to (131)I therapy are well documented, there is little in the literature addressing nasolacrimal duct obstruction (NLDO). We aimed to evaluate the frequency of (131)I therapy-acquired NLDO, its correlation to (131)I therapy doses, and the surgical treatment outcome of this rare side effect.
METHODS
From 2000-2012, a retrospective review of 864 among 1,192 patients with confirmed DTC who were treated with (131)I therapy was performed to examine the frequency of NLDO, its causative factors, as well as imaging, surgical intervention, and outcomes.
RESULTS
Nineteen (2.2%) patients were identified with NLDO. The mean age was 51.9±10.5 years (range: 39-72 years). Fifteen (78.9%) were female and four were male (21.1%). The mean individual (131)I doses were 311.1±169.3 millicurie (mCi) (range: 150-600 mCi). The mean duration between the date of (131)I therapy and the occurrence of NLDO was 11.6±4.1 months (range: 6.5-20). Fourteen (73.7%) patients had bilateral epiphora. Computed tomography dacryography allowed for the detection of all NLDO. Eighteen (94.7%) patients underwent dacryocystorhinostomy. Complete recovery was obtained in 14 (73.7%) patients. Age >45 years and (131)I therapy doses >150 mCi were significantly correlated with NLDO (P=0.02 and P=0.03, respectively).
CONCLUSION
NLDO is an underestimated complication of (131)I therapy in DTC patients. Clinicians should be aware of this rare complication for prompt intervention.
PubMed: 25525325
DOI: 10.2147/OPTH.S71708 -
Cancer Jun 2009Samarium-153 ethylenediaminetetramethylene phosphonic acid ((153)Sm-EDTMP) has been used to treat patients with high-risk osteosarcoma. The purpose of the current study... (Clinical Trial)
Clinical Trial
BACKGROUND
Samarium-153 ethylenediaminetetramethylene phosphonic acid ((153)Sm-EDTMP) has been used to treat patients with high-risk osteosarcoma. The purpose of the current study was to determine the maximally tolerated dose of (153)Sm-EDTMP that permits hematopoietic recovery within 6 weeks.
METHODS
Patients with recurrent or refractory osteosarcoma with bone metastases were enrolled in this study. Subjects were treated with increasing doses of (153)Sm-EDTMP, beginning with 1.0 millicuries (mCi)/kg and followed initially with 40% increment dose level escalations, using a continual reassessment method for dose escalation and de-escalation with a target dose-limiting toxicity (DLT) rate of 30%. Complete blood counts were monitored weekly, and the primary DLT was defined as failure to achieve an absolute neutrophil count >750/mm(3) and a platelet count >75,000/mm(3) within 6 weeks of treatment. In addition to assessing toxicity, dosimetry measurements were made to estimate the radiation dose delivered to target lesions.
RESULTS
The maximally tolerated dose of (153)Sm-EDTMP was 44.8 megabecquerel (MBq)/kg (1.21 mCi/kg). DLTs were confined to hematologic toxicities, particularly delayed platelet recovery in 2 patients treated at a dose of 51.8 MBq/kg (1.4 mCi/kg). Grade 2 and 3 pulmonary toxicity (graded according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) as reported in 2 patients (at administered activities of 44.8 MBq/kg and 51.8 MBq/kg) was attributable to progressive pulmonary disease. No other significant nonhematologic toxicities were observed.
CONCLUSIONS
Patients with osteosarcoma who have previously been heavily treated with chemotherapy can be safely administered (153)Sm-EDTMP with rapid hematologic recovery. The data from the current study support the development of a future trial to assess the efficacy of combining targeted radiotherapy with cytotoxic chemotherapy as a treatment option for patients with high-risk osteosarcoma.
Topics: Adolescent; Adult; Blood Cell Count; Bone Neoplasms; Child; Female; Humans; Male; Maximum Tolerated Dose; Neutropenia; Organometallic Compounds; Organophosphorus Compounds; Osteosarcoma; Prognosis; Radiometry; Radiotherapy Dosage; Thrombocytopenia; Treatment Outcome
PubMed: 19338063
DOI: 10.1002/cncr.24286 -
Plant Physiology Jan 1987Immature seeds of apricot (Prunus armeniaca L.) were fed the native gibberellin A(5) (GA(5)) as 1- and 1,2-[(3)H]GA(5) (5.3 Curies per millimole to 16 milliCuries per...
Immature seeds of apricot (Prunus armeniaca L.) were fed the native gibberellin A(5) (GA(5)) as 1- and 1,2-[(3)H]GA(5) (5.3 Curies per millimole to 16 milliCuries per millimole) at doses (42 nanograms to 10.6 micrograms per seed) 2 to 530 times the expected endogenous level. After 4 days of incubation, seeds were extracted and free [(3)H]GA-like metabolites were separated from the highly H(2)O-soluble [(3)H]metabolites. For high specific activity feeds the retention times (Rts) of radioactive peaks were compared with Rts of authentic GAs on sequential gradient-eluted --> isocratic eluted reversed-phase C(18) high performance liquid chromatography (HPLC) -radiocounting (RC). From high substrate feeds (530 and 230 x expected endogenous levels) HPLC-RC peak groupings were subjected to capillary gas chromatography-selected ion monitoring (GC-SIM), usually six characteristic ions. The major free GA metabolites of [(3)H] GA(5) were identified as GA(1), GA(3), and GA(6) by GC-SIM. The major highly water soluble metabolite of [(3)H]GA(5) at all levels of substrate GA(5) had chromatographic characteristics similar to authentic GA(1)-glucosyl ester. Expressed as a percentage of recovered radioactivity, low substrate [(3)H]GA(5) feeds (2 x expected endogenous level) yielded a broad spectrum of metabolites eluting at the Rts where GA(1), GA(3), GA(5) methyl ester, GA(6), GA(22), GA(29) (17, 14, 1.6, 7, 1.1, 0.5%, respectively) and GA glucosyl conjugates of GA(1), GA(3), GA(5), and GA(8) (33, 11, 1, 0.1%, respectively) elute. Metabolites were also present at Rts where GA glucosyl conjugates of GA(6) and GA(29) would be expected to elute (8 and 0.1%, respectively). Only 5% of the radioactivity remained as GA(5). Increasing substrate GA(5) levels increased the proportion of metabolites with HPLC Rts similar to GA(1), GA(6), and especially GA(1) glucosyl ester, primarily at the expense of metabolites with HPLC Rts similar to GA(3), GA(3)-glucosyl ester, and a postulated conjugate of GA(6). There was evidence that high doses of substrate GA(5) induced new metabolites which often, but not always, differed from GA(1), GA(3), and GA(6) in HPLC Rt. These same metabolites, when analyzed by GC-SIM yielded m/e ions the same as the M(+) and other characteristic m/e ions of the above GAs, albeit at differing GC Rt and relative intensities.
PubMed: 16665189
DOI: 10.1104/pp.83.1.137 -
Blood Aug 1999Delivery of targeted hematopoietic irradiation using radiolabeled monoclonal antibody may improve the outcome of marrow transplantation for advanced acute leukemia by... (Clinical Trial)
Clinical Trial
Delivery of targeted hematopoietic irradiation using radiolabeled monoclonal antibody may improve the outcome of marrow transplantation for advanced acute leukemia by decreasing relapse without increasing toxicity. We conducted a phase I study that examined the biodistribution of (131)I-labeled anti-CD45 antibody and determined the toxicity of escalating doses of targeted radiation combined with 120 mg/kg cyclophosphamide (CY) and 12 Gy total body irradiation (TBI) followed by HLA-matched related allogeneic or autologous transplant. Forty-four patients with advanced acute leukemia or myelodysplasia received a biodistribution dose of 0.5 mg/kg (131)I-BC8 (murine anti-CD45) antibody. The mean +/- SEM estimated radiation absorbed dose (centigray per millicurie of (131)I) delivered to bone marrow and spleen was 6.5 +/- 0.5 and 13.5 +/- 1.3, respectively, with liver, lung, kidney, and total body receiving lower amounts of 2.8 +/- 0.2, 1.8 +/- 0.1, 0.6 +/- 0.04, and 0.4 +/- 0.02, respectively. Thirty-seven patients (84%) had favorable biodistribution of antibody, with a higher estimated radiation absorbed dose to marrow and spleen than to normal organs. Thirty-four patients received a therapeutic dose of (131)I-antibody labeled with 76 to 612 mCi (131)I to deliver estimated radiation absorbed doses to liver (normal organ receiving the highest dose) of 3.5 Gy (level 1) to 12.25 Gy (level 6) in addition to CY and TBI. The maximum tolerated dose was level 5 (delivering 10.5 Gy to liver), with grade III/IV mucositis in 2 of 2 patients treated at level 6. Of 25 treated patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS), 7 survive disease-free 15 to 89 months (median, 65 months) posttransplant. Of 9 treated patients with acute lymphoblastic leukemia (ALL), 3 survive disease-free 19, 54, and 66 months posttransplant. We conclude that (131)I-anti-CD45 antibody can safely deliver substantial supplemental doses of radiation to bone marrow (approximately 24 Gy) and spleen (approximately 50 Gy) when combined with conventional CY/TBI.
Topics: Acute Disease; Adolescent; Adult; Antibodies; Antineoplastic Agents, Alkylating; Bone Marrow Transplantation; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Female; Graft Survival; Humans; Iodine Radioisotopes; Leukemia; Leukocyte Common Antigens; Male; Middle Aged; Myelodysplastic Syndromes; Transplantation, Autologous; Transplantation, Homologous; Whole-Body Irradiation
PubMed: 10438711
DOI: No ID Found -
Cancer Sep 2011Adolescent and adult patients with neuroblastoma appear to have a more indolent disease course but a lower survival rate compared with their younger counterparts. The...
BACKGROUND
Adolescent and adult patients with neuroblastoma appear to have a more indolent disease course but a lower survival rate compared with their younger counterparts. The majority of neuroblastoma tumors specifically accumulate the radiolabeled norepinephrine analogue iodine-131-metaiodobenzylguanidine ((131) I-MIBG). Therefore, (131) I-MIBG has become increasingly used as targeted radiotherapy for patients with recurrent or refractory neuroblastoma. The objective of the current study was to characterize the toxicity and activity of this therapy in older patients.
METHODS
The authors performed a retrospective analysis of 39 consecutive patients aged ≥10 years with recurrent or refractory neuroblastoma who were treated with (131) I-MIBG monotherapy at the University of California at San Francisco under phase 1, phase 2, and compassionate access protocols.
RESULTS
Sixteen patients were aged ≥18 years at the time of MIBG treatment initiation, whereas 23 patients were ages 10 to 17 years. The median cumulative administered dose of (131) I-MIBG was 17.8 millicuries (mCi)/kg. The majority of treatments led to grade 3 or 4 hematologic toxicities (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3]) that were similar in frequency among age strata. Three patients subsequently developed a hematologic malignancy or myelodysplasia. The overall rate of complete plus partial response was 46%. Patients aged ≥18 years at the time of first MIBG treatment had a significantly higher response rate compared with patients ages 10 to 17 years (56% vs 39%; P = .023). The median overall survival was 23 months with a trend toward longer overall survival for the subgroup of patients aged ≥18 years (P = .12).
CONCLUSIONS
The findings of the current study suggest that (131) I-MIBG is a highly effective salvage agent for adolescents and adults with neuroblastoma.
Topics: 3-Iodobenzylguanidine; Adolescent; Adult; Antineoplastic Agents; Child; Clinical Trials as Topic; Female; Humans; Male; Neuroblastoma; Radiopharmaceuticals; Recurrence; Survival Rate; Treatment Outcome
PubMed: 21387264
DOI: 10.1002/cncr.25987 -
Radiology Case Reports Mar 2017I-131 uptake in the breast has been described with a variety of normal and pathologic conditions. We present the case of a 38-year-old female who received 317...
I-131 uptake in the breast has been described with a variety of normal and pathologic conditions. We present the case of a 38-year-old female who received 317 millicuries of radioactive I-131 treatment for papillary thyroid carcinoma. Post-treatment scan demonstrated I-131 uptake in an area of fat necrosis in the breast.
PubMed: 28228903
DOI: 10.1016/j.radcr.2016.10.018 -
Plant Physiology Nov 1991Resistance to the fungal plant pathogen Cochliobolus carbonum race 1 and to its host-selective toxin, HC-toxin, is determined by Hm, a single dominant gene in the host...
Resistance to the fungal plant pathogen Cochliobolus carbonum race 1 and to its host-selective toxin, HC-toxin, is determined by Hm, a single dominant gene in the host plant maize, (Zea mays L). Radiolabeled HC-toxin of specific activity 70 milliCuries per millimole, prepared by feeding tritiated d,l-alanine to the fungus, was used to study its fate in maize leaf tissues. HC-toxin was converted by resistant leaf segments to a single compound, identified by mass spectrometry and nuclear magnetic resonance as the 8-hydroxy derivative of HC-toxin formed by reduction of the 8-keto group of 2-amino-9, 10-epoxy-8-oxo-decanoic acid, one of the amino acids in HC-toxin. Reduction of HC-toxin occurred in cell-free preparations from etiolated (Hm/hm) maize shoots, and the activity was sensitive to heat and proteolytic digestion, dependent on NADPH, and inhibited by p-hydroxymercuribenzoate and disulfiram. The enzyme (from the Hm/hm genotype) was partially purified by ammonium sulfate precipitation and diethylaminoethyl-ion exchange chromatography. By gel filtration chromatography, the enzyme had a molecular weight of 42,000. NADH was approximately 30% as effective as NADPH as a hydride donor, and flavin-containing cofactors had no effect on activity. When HC-toxin was introduced to maize leaf segments through the transpiration stream, leaf segments from both resistant and susceptible maize inactivated toxin equally well over a time-course of 9 hours. Although these data suggest no relationship between toxin metabolism and host selectivity, we discuss findings in apparent conflict with the current data and describe why the relationship between enzymatic reduction of HC-toxin and Hm remains unresolved.
PubMed: 16668492
DOI: 10.1104/pp.97.3.1080 -
Journal of Nuclear Medicine : Official... Dec 1985We report an improved method for the synthesis and purification of [11C]methylcholine from the precursors [11C]methyliodide and 2-dimethylaminoethanol (deanol)....
We report an improved method for the synthesis and purification of [11C]methylcholine from the precursors [11C]methyliodide and 2-dimethylaminoethanol (deanol). Preparation time, including purification, is 35 min postbombardment. Forty millicuries of purified injectable [11C]choline were produced with a measured specific activity of greater than 300 Ci/mmol and a radiochemical purity greater than 98%. The decay corrected radiochemical yield for the synthesis and purification was approximately 50%. Residual precursor deanol, which inhibits brain uptake of choline, is removed by a rapid preparative high performance liquid chromatography (HPLC) method using a reverse phase cyano column with a biologically compatible 100% water eluent. Evaporation alone did not completely remove the deanol precursor. Brain uptake of the [11C]choline product was six times greater after HPLC removal of deanol because doses of less than 1 microgram/kg significantly inhibit [14C]choline brain uptake.
Topics: Animals; Brain; Carbon Radioisotopes; Choline; Chromatography, High Pressure Liquid; Deanol; Ethanolamines; Hydrocarbons, Iodinated; Male; Radionuclide Generators; Rats; Tomography, Emission-Computed
PubMed: 3877796
DOI: No ID Found -
Imaging receptor for advanced glycation end product expression in mouse model of hind limb ischemia.EJNMMI Research May 2013The purpose of this study is to image the effect of diabetes on expression of receptor for advanced glycation endproducts (RAGE) in limb ischemia in live animals.
BACKGROUND
The purpose of this study is to image the effect of diabetes on expression of receptor for advanced glycation endproducts (RAGE) in limb ischemia in live animals.
METHODS
Male wild-type C57BL/6 mice were either made diabetic or left as control. Two months later, diabetic and non-diabetic mice underwent left femoral artery ligation. The right leg served as lesion control. Five days later, mice were injected with 15.1 ± 4.4 MBq 99mTc-anti-RAGE F(ab')2 and 4 to 5 h later (blood pool clearance) underwent SPECT/CT imaging. At the completion of imaging, mice were euthanized, hind limbs counted and sectioned, and scans reconstructed. Regions of interest were drawn on serial transverse sections comprising the hind limbs and activity in millicuries summed and divided by the injected dose (ID). Quantitative histology was performed for RAGE staining and angiogenesis.
RESULTS
Uptake of 99mTc-anti-RAGE F(ab')2 as %ID × 10-3 was higher in the left (ischemic) limbs for the diabetic mice (n = 8) compared to non-diabetic mice (n = 8) (1.20 ± 0.44% vs. 0.49 ± 0.40%; P = 0.0007) and corresponded to less angiogenesis in the diabetic mice. Uptake was also higher in the right limbs of diabetic compared to non-diabetic animals (0.82 ± 0.33% vs. 0.40 ± 0.14%; P = 0.0004).
CONCLUSIONS
These data show the feasibility of imaging and quantifying the effect of diabetes on RAGE expression in limb ischemia.
PubMed: 23663412
DOI: 10.1186/2191-219X-3-37 -
California Medicine Apr 1949Fifty patients with uncomplicated Graves' disease were treated with radioactive iodine (I(131)). Twenty-six patients who were followed for one year or longer are the...
Fifty patients with uncomplicated Graves' disease were treated with radioactive iodine (I(131)). Twenty-six patients who were followed for one year or longer are the basis of this report. Twenty-five are now euthyroid; only one is not completely well. The total dose of radioiodine administered varied from 0.5 to 10 millicuries. The average length of time necessary for return to a euthyroid state was from three to four months. Hypometabolism developed in three patients, and in one the signs and symptoms of myxedema developed. No other complications ensued. One patient who apparently relapsed had complete return to normal after further iodine administration. The determination of the uptake of radioactive iodine by the thyroid gland is a useful diagnostic procedure in differentiating conditions simulating hyperthyroidism.Following treatment with radioactive iodine, the thyroid gland becomes smaller, the uptake of iodine by the gland is reduced, and the level of organic iodine in the plasma becomes normal. In acute thyroiditis, in spite of a high basal metabolic rate, high content of organic iodine in the plasma and other evidences of "hyperthyroidism," the uptake of I(131) has been very low.
Topics: Graves Disease; Humans; Hyperthyroidism; Iodine; Iodine Radioisotopes; Middle Aged; Myxedema; Thyroiditis
PubMed: 18116225
DOI: No ID Found