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Journal of Nuclear Medicine : Official... Aug 1999Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced therapeutic responses in patients with non-Hodgkin's lymphoma (NHL) and... (Clinical Trial)
Clinical Trial
UNLABELLED
Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced therapeutic responses in patients with non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL) when labeled with 131I. Responders had statistically significant prolongation of survival compared with nonresponders. The nonmyeloablative, maximum tolerated dose for each of two doses of 131I-Lym-1 was 3.7 GBq/m2 (total 7.4 GBq/m2 [100 mCi/m2, total 200 mCi/m2]) of body surface area. The purpose of this study was to determine the pharmacokinetics and radiation dosimetry for the initial 131I-Lym-1 therapy dose in patients with NHL and CLL and to compare tumor dosimetry with 131I-Lym-1 dosing and other patient parameters.
METHODS
Fifty-one patients with stage 3 or 4 lymphoma were treated with 131I-Lym-1 (0.74-8.04 GBq [20-217 mCi]) in either a maximum tolerated dose (MTD) or low-dose (LD) trial. Total Lym-1 given to each patient was sufficient in all instances to exceed the threshold required for stable pharmacokinetics. Quantitative imaging and physical examination, including caliper and CT measurement of tumor size and analysis of blood, urine and feces, were performed for a period of 7 to 10 d after infusion to assess pharmacokinetics and radiation dosimetry. Clinical records were reviewed to obtain data required for comparative assessments.
RESULTS
The concentration (%ID/g) and biologic half-time of 131-Lym-1 in tumor were about twice those in normal tissues, although tumor half-time was similar to that of the thyroid. Pharmacokinetics were similar for patients in the MTD and LD trials, and for NHL and CLL patients in the LD trial, except that the latter group had less tumor concentration of 131I. Mean tumor radiation dose per unit of administered 131I was 1.0 Gy/GBq (3.7 rad/mCi) for patients with NHL whether in MTD or LD trials, about nine times greater than that for body or marrow. Tumor radiation dose was less and liver radiation dose was more in patients with CLL. Otherwise, radiation dosimetry was, on average, remarkably similar among groups of patients and among individual patients. Pharmacokinetics and dosimetry did not appear to be influenced by the amount of 131I or Lym-1 within the ranges administered. Tumor concentration of 131I and radiation dose per gigabecquerel were inversely related to tumor size but did not seem to be related to histologic grade or type, tumor burden or therapeutic response.
CONCLUSION
The therapeutic index of 131I-Lym-1 was favorable, although the index for patients with CLL was less than that for patients with NHL. Pharmacokinetics and radiation dosimetry were, on average, remarkably similar among patients and groups of patients in different trials.
Topics: Adult; Aged; Antibodies, Monoclonal; Binding Sites; Female; Humans; Iodine Radioisotopes; L-Lactate Dehydrogenase; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Male; Middle Aged; Radioimmunotherapy; Radiometry; Radiopharmaceuticals; Splenectomy
PubMed: 10450684
DOI: No ID Found -
Indian Journal of Nuclear Medicine :... 2022The production of nitrogen-13 (N)-NH by ethanol method using automated synthesizer and accessing the production yield, quality control for clinical application.
AIMS
The production of nitrogen-13 (N)-NH by ethanol method using automated synthesizer and accessing the production yield, quality control for clinical application.
CONTEXT
N, together with F, O, and C, is one of the positron emitters that can be produced on the multi-gigabecquerel scale in biomedical cyclotrons. (N)-ammonia is frequently used for cardiac PET studies. It is widely applied for the evaluation of myocardial perfusion in the clinical assessment of cardiac disorders. Simple, fast, and reliable preparation methods have contributed to the routine application of this tracer. Although only two methods are available, a challenge remains to adopt a more efficient and consistent approach to its production. For clinical application, routine production of this tracer is mandatory in compliance with regulatory guidelines. Being at hospital radiopharmacy it is our responsibility to support the clinical service with uninterrupted production and supply of (N)-NH.
MATERIALS AND METHODS
The chemicals were used commercially available from Sigma Aldrich, India, Ltd., and Fisher Scientific, India, Ltd. (Mumbai, India), Sep-Pak CM cartridges (Waters India, Pvt., Ltd.,). Radio-thin layer chromatography was carried out using aluminum sheets precoated with silica gel 60 F254 (E. Merck, India).
RESULTS
The protocol developed with MPS-100 synthesizer yield (N)-NH95-97% (EOB) with a synthesis time of around 7 min.
CONCLUSIONS
With the installation of HM-18 cyclotron at our hospital, center is capable to produce (N)-NH of good yield and purity through the ethanol method, for mycocardial perfusion studies. Our protocol is simple, reproducible, and robust.
PubMed: 35478690
DOI: 10.4103/ijnm.ijnm_92_21 -
Plant Physiology 1987[3H]Gibberellin A20 (GA20) of high specific radioactivity (49.9 gigabecquerel per millimole) was applied equilaterally in a ring of microdrops to the internodal pulvinus...
[3H]Gibberellin A20 (GA20) of high specific radioactivity (49.9 gigabecquerel per millimole) was applied equilaterally in a ring of microdrops to the internodal pulvinus of shoots of 3-week-old gravistimulated and vertical normal maize (Zea mays L.), and to a pleiogravitropic (prostrate) maize mutant, lazy (la). All plants converted the [3H]GA20 to [3H]GA1- and [3H]GA29-like metabolites as well as to several metabolites with the partitioning and chromatographic behavior of glucosyl conjugates of [3H]GA1, [3H]GA29, and [3H]GA8. The tentative identification of these putative [3H]GA glucosyl conjugates was further supported by the release of the free [3H]GA moiety after cleavage with cellulase. Within 12 hours of the [3H]GA20 feed, there was a significantly higher proportion of total radioactivity in lower than in upper halves of internode and leaf sheath pulvini in gravistimulated normal maize. Further, there was a significantly higher proportion of putative free GA metabolites of [3H]GA20, especially [3H]GA1, in the lower halves of normal maize relative to upper halves. The differential localization of the metabolites between upper and lower halves was not apparent in the pleiogravitropic mutant, la. Endogenous GA-like substances were also examined in gravistimulated maize shoots. Forty-eight hours after gravistimulation of 3-week-old maize seedlings, endogenous free GA-like substances in upper and lower leaf sheath and internode pulvini halves were extracted, chromatographed, and bioassayed using the "Tanginbozu" dwarf rice microdrop assay. Lower halves contained consistently higher total levels of GA-like activity. The qualitative elution profile of GA-like substances differed consistently, upper halves containing principally a GA20-like substance and lower halves containing principally a GA20-like substance and lower halves containing mainly GA1-like and GA19-like substances. Gibberellins A1 (10 nanograms per gram) and A20 (5 nanograms per gram) were identified from these lower leaf sheath pulvini by capillary gas chromatography-selected ion monitoring. Results from all of these experiments are consistent with a role for GAs in the differential shoot growth that follows gravitropism, although the results do not eliminate the possibility that the redistribution of GAs results from the gravitropic response.
Topics: Gibberellins; Gravitation; Gravitropism; Plant Growth Regulators; Plant Proteins; Plant Shoots; Zea mays
PubMed: 11539033
DOI: 10.1104/pp.83.3.645 -
Journal of Nuclear Medicine : Official... Jan 2005Radiolabeling of monoclonal antibodies (mAbs) with an intracellularly trapped form of (131)I (residualizing (131)I) involves radioiodinating a small molecular entity,...
UNLABELLED
Radiolabeling of monoclonal antibodies (mAbs) with an intracellularly trapped form of (131)I (residualizing (131)I) involves radioiodinating a small molecular entity, conjugating it to the mAb, and purification. Column purifications are impractical during procedures involving multi-gigabecquerel levels of radioactivity. The goal of this study was to develop a simple, remote, "1-pot" method of radiolabeling and purification for the scaled-up radioiodination of a humanized anti-carcinoembryonic antigen (CEA) mAb, humanized MN-14 (hMN-14; labetuzumab), with an optimized residualizing (131)I moiety, (131)I-IMP-R4. IMP-R4 is MCC-Lys(MCC)-Lys(X)-d-Tyr-d-Lys(X)-OH, where MCC is 4-(N-maleimidomethyl)-cyclohexane-1-carbonyl and X is 1-((4-thiocarbonylamino)benzyl)-diethylenetriaminepentaacetic acid.
METHODS
An IODO-GEN-based remote labeling system was used. IMP-R4 was radioiodinated (0.13 mumol per 3.7 GBq of (131)I) at a pH of 7.0-7.4 and conjugated to disulfide-reduced hMN-14 after quenching of unused reactive (131)I. The product was purified by stirring for 5 min with a 20% (w/v) suspension of an anion-exchange resin and sterilely filtered into a sealed vial. Human serum albumin was added at a final concentration of 1%-2.5%. Immunoreactivity was determined by mixing with CEA and determining the complexation level by size-exclusion high-pressure liquid chromatography. Two control radiolabelings, either with unreduced hMN-14 or with IMP-R4 omitted, also were performed.
RESULTS
In 18 radiolabelings with (131)I in the range of 2.04-4.81 GBq (55-130 mCi), yields of 59.9% +/- 7.9% (mean +/- SD) at specific activities of 200 +/- 26 MBq/mg (5.4 +/- 0.7 mCi/mg) were obtained, with > or =95% of the radioactivity being associated with hMN-14 and with < or =4% aggregation. Similar yields were obtained in a subset of radiolabelings (n = 7) with >3.7 GBq of (131)I. The immunoreactivities of the preparations were typically >95%. Nonspecific incorporation in the absence of IMP-R4 was 0.5%, whereas that obtained with unreduced IgG was approximately 8%, possibly because of conjugation of IMP-R4 at lysine sites. The process also removed >99% of the quenching reagent used. Radiolabelings performed with freshly prepared solutions or lyophilized preparations produced similar yields, a result that suggested the option for a single-use kit design.
CONCLUSION
Efficient removal of (131)I-IMP-R4 and quenched (131)I by 5 min of stirring with anion-exchange resin renders a multi-gigabecquerel-level preparation of (131)I-IMP-R4-hMN-14 safe, convenient, and practical.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Carcinoembryonic Antigen; Drug Stability; Humans; Isotope Labeling; Oligopeptides; Pentetic Acid; Radioimmunotherapy; Radiopharmaceuticals
PubMed: 15632046
DOI: No ID Found -
Journal of Nuclear Medicine : Official... Jun 2001In some patients with well-differentiated thyroid carcinoma, dosimetry is necessary to avoid toxicity from therapy and to guide prescription of the administered activity...
UNLABELLED
In some patients with well-differentiated thyroid carcinoma, dosimetry is necessary to avoid toxicity from therapy and to guide prescription of the administered activity of radioiodine.
METHODS
The presentations and courses of 2 patients exemplify the points. In the second patient, the clues to the need for dosimetry were the large size of the tumor and high circulating levels of thyroxine in the absence of exogenous hormone. The other patient manifested hyperthyroidism from stimulation of the tumors by thyroid-stimulating immunoglobulin. Dosimetry was performed by published methods.
RESULTS
Dosimetry of radioactivity in the body and blood warned of increased irradiation per gigabecquerel of administered (131)I. In each patient, the tumors sequestered a substantial amount of administered (131)I and secreted (131)I-labeled hormones that circulated for days. In 1 patient, the blood time--activity curve was complex, making a broad range of predictions for irradiation to blood and bone marrow. Still, dosimetry gave information that helped to avoid severe toxicity. At, respectively, 1.85 and 2.2 GBq (131)I, initial treatments were relatively low. There was a modest escalation in subsequent administered activities. Leukopenia with neutropenia developed in each patient, and one had moderate thrombocytopenia and anemia, but toxicity appeared to be transient. Each patient had a marked increase in well-being and evidence of reduced tumor function and volume.
CONCLUSION
Two patients with advanced, well-differentiated thyroid carcinoma illustrate the need for dosimetry to help prevent toxicity to normal tissues from therapeutic radioiodine. Conversion of radioiodide to circulating radiothyroxine by functioning carcinomas increases the absorbed radiation in normal tissues. Yet, dosimetric data acquired for 4 d or more may be insufficient for accurate calculations of absorbed radiation in blood. Guidelines suggested for avoiding toxicity are based on the circulating thyroxine concentrations, the presence of thyroid stimulators, the amount of radioactivity retained in the body at 48 h, and the general status of the patient.
Topics: Aged; Carcinoma, Papillary; Female; Humans; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Middle Aged; Radionuclide Imaging; Radiotherapy Dosage; Thyroid Neoplasms; Thyroxine
PubMed: 11390565
DOI: No ID Found -
Hormone and Metabolic Research =... Oct 2023The study was to evaluate the effect of radioactive iodine (RAI) treatment application time and clinical, histopathological factors on ablation success in patients with...
The study was to evaluate the effect of radioactive iodine (RAI) treatment application time and clinical, histopathological factors on ablation success in patients with operated papillary thyroid cancer (PTC) in low and intermediate-risk. One hundred sixty-one patients with PTC in the low and intermediate-risk were evaluated. Most patients (89.4%) were in the low-risk, and 10.6% were in the intermediate-risk. When the patients were divided into two groups according to the date of receiving RAI treatment after surgery, those who received early treatment (≤3 months) constituted the majority of the patients (72.7%). Seventeen patients received 1.85 Gigabecquerel (GBq), 119 3.7 GBq, 25 5.55 GBq RAI. Most patients (82%) achieved ablation success after the first RAI treatment. The time interval between surgery and RAI treatment did not affect ablation success. Stimulated Tg level measured on the RAI treatment day was an independent predictive factor for successful ablation (p<0.001). The cut-off value of Tg found to predict ablation failure was 5.86 ng/ml. It was concluded that 5.55 GBq RAI treatment could predict ablation success compared to 1.85 GBq dose (p=0.017). It was concluded that having a T1 tumor may predict treatment success compared to a T2 or T3 tumor (p=0.001, p<0.001, retrospectively). The time interval does not affect ablation success in low and intermediate-risk PTC. The ablation success rate may decrease in patients who receive low-dose RAI and have high Tg levels before treatment. The most crucial factor in achieving ablation success is giving enough doses of RAI to ablate the residual tissue.
Topics: Humans; Thyroid Cancer, Papillary; Iodine Radioisotopes; Thyroid Neoplasms; Retrospective Studies; Carcinoma, Papillary; Thyroidectomy
PubMed: 37267999
DOI: 10.1055/a-2077-7246 -
Frontiers in Radiology 2024Due to a lack of data, there is an ongoing debate regarding the optimal frontline interventional therapy for unresectable hepatocellular carcinoma (HCC). The aim of the...
Outcome of transarterial radioembolization in patients with hepatocellular carcinoma as a first-line interventional therapy and after a previous transarterial chemoembolization.
PURPOSE
Due to a lack of data, there is an ongoing debate regarding the optimal frontline interventional therapy for unresectable hepatocellular carcinoma (HCC). The aim of the study is to compare the results of transarterial radioembolization (TARE) as the first-line therapy and as a subsequent therapy following prior transarterial chemoembolization (TACE) in these patients.
METHODS
A total of 83 patients were evaluated, with 38 patients having undergone at least one TACE session prior to TARE [27 male; mean age 67.2 years; 68.4% stage Barcelona clinic liver cancer (BCLC) B, 31.6% BCLC C]; 45 patients underwent primary TARE (33 male; mean age 69.9 years; 40% BCLC B, 58% BCLC C). Clinical [age, gender, BCLC stage, activity in gigabecquerel (GBq), Child-Pugh status, portal vein thrombosis, tumor volume] and procedural [overall survival (OS), local tumor control (LTC), and progression-free survival (PFS)] data were compared. A regression analysis was performed to evaluate OS, LTC, and PFS.
RESULTS
No differences were found in OS (95% CI: 1.12, = 0.289), LTC (95% CI: 0.003, = 0.95), and PFS (95% CI: 0.4, = 0.525). The regression analysis revealed a relationship between Child-Pugh score (= 0.005), size of HCC lesions (>10 cm) (= 0.022), and OS; neither prior TACE (Child-Pugh B patients; 95% CI: 0.120, = 0.729) nor number of lesions (>10; 95% CI: 2.930, = 0.087) correlated with OS.
CONCLUSION
Prior TACE does not affect the outcome of TARE in unresectable HCC.
PubMed: 38445105
DOI: 10.3389/fradi.2024.1346550