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Iodine-125 seed implantation for synchronous pancreatic metastases from hepatocellular carcinoma: A case report and literature review

Rationale The image-guided iodine-125 seed implantation has been widely used for a variety of tumors, including prostatic cancer, pulmonary cancer, hepatocellular carcinoma and pancreatic cancer. However, the clinical value of iodine-125 seed implantation for the treatment of pancreatic metastasis from hepatocellular carcinoma has not been reported. We presented the first case with ultrasound-guided iodine-125 seed implantation for this disease. Patient concerns We presented the case of a 48-year-old man patient with primary hepatocellular carcinoma and pancreatic metastasis who was managed with ultrasound-guided iodine-125 seeds implantation. Diagnoses She was diagnosed with synchronous pancreatic metastases from hepatocellular carcinoma. Interventions Puncture biopsy and ultrasound-guided iodine-125 seeds implantation. Outcomes The hepatic and pancreatic tumors were obviously reduced after 15 months. Moreover, the liver function test was mildly abnormal in glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase. Lessons The image-guided iodine-125 seeds implantation was an important therapeutic approache to unresectable hepatocellular carcinoma with pancreatic metastasis. However, more related cases should be reported for further evaluating the value of the way.

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https://www.researchgate.net/......


Studies on 177Lu-labeled methylene diphosphonate as potential bone-seeking radiopharmaceutical for bone pain palliation.

Abstract

OBJECTIVE:

(99m)Tc-MDP (technetium-99(m)-labeled methylene diphosphonate) has been widely used as a radiopharmaceutical for bone scintigraphy in cases of metastatic bone disease. (177)Lu is presently considered as an excellent radionuclide for developing bone pain palliation agents. No study on preparing a complex of (177)Lu with MDP has been reported yet. Based on these facts, it was hypothesized that a bone-seeking (177)Lu-MDP (lutetium-177-labeled MDP) radiopharmaceutical could be developed as an agent for palliative radiotherapy of bone pain due to skeletal metastases. Biodistribution studies after intravenous injection of (177)Lu-MDP complex in rats may yield important information to assess its potential for clinical use as a bone pain palliation agent for the treatment of bone metastases.

METHODS:

(177)Lu was produced by irradiating natural Lu(2)O(3) (10 mg) target at a thermal flux ∼ 8.0 × 10(13) n/cm(2) per second for 12 h in the swimming pool-type reactor.(177)Lu was labeled with MDP by adding nearly 37 MBq (1.0 mCi) of (177)LuCl(3) to a vial containing 10 mg MDP. The radiochemical purity and labeling efficiencies were determined by thin layer chromatography. Labeling of (177)Lu with MDP was optimized, and one sample was subjected to high-performance liquid chromatography (HPLC) analysis. Twelve Sprague-Dawley rats were injected with 18.5 MBq (0.5 mCi). (177)Lu-MDP in a volume of 0.1 ml was injected intravenously and then sacrificed at 2 min, 1 h, 2 h and 22 h (three rats at each time point) after injection. Samples of various organs were separated, weighed and measured for radioactivity and expressed as percent uptake of injected dose per gram. Bioevaluation studies with rats under gamma-camera were also performed to verify the results.

RESULTS:

The quality control using thin layer chromatography has shown >99% radiochemical purity of (177)Lu-MDP complex. Chromatography with Whatman 3MM paper showed maximum labeling at pH = 6, incubation time = 30 min, and ligand/metal ratio = 60:1. HPLC analysis showed 1.35 ± 0.05 min retention time of (177)Lu-MDP complex. No decrease in labeling was observed at higher temperatures, and the stability of the complex was found adequate. Biodistribution studies of (177)Lu-MDP revealed high skeletal uptake, i.e., 31.29 ± 1.27% of the injected dose at 22 h post injection. Gamma-camera images of (177)Lu-MDP in Sprague-Dawley rats also showed high skeletal uptake and verified the results.

CONCLUSION:

The study demonstrated that MDP could be labeled with (177)Lu with high radiochemical yields (>99%). The in vitro stability of the complex was found adequate. Biodistribution studies in Sprague-Dawley rats indicated selective bone accumulation, relatively low uptake in soft tissue (except liver) and higher skeletal uptake, suggesting that it may be useful as a bone pain palliation agent for the treatment of bone metastases.

The information comes from:
https://www.ncbi.nlm.nih.gov/pubmed/21492790


Estimation of whole body radiation exposure to nuclear medicine personnel during synthesis of 177lutetium-labeled radiopharmaceuticals

Abstract

Purpose of the Study: With rapid development in the field of nuclear medicine therapy, radiation safety of the personnel involved in synthesis of radiopharmaceuticals has become imperative. Few studies have been done on estimating the radiation exposure of personnel involved in the radio labeling of 177Lu-compounds in western countries. However, data from the Indian subcontinent are limited. We have estimated whole body radiation exposure to the radiopharmacist involved in the labeling of: 177Lu-DOTATATE, 177Lu-PSMA-617, and 177Lu-EDTMP. Materials and Methods: Background radiation was measured by keeping a pocket dosimeter around the workbench when no radioactive work was conducted. The same pocket dosimeter was given to the radiopharmacist performing the labeling of 177Lu-compounds. All radiopharmaceuticals were synthesized by the same radiopharmacist with 3, 1 and 3 year experience, respectively, in radiolabeling the above compounds. Results: One Curie (1 Ci) of 177Lu was received fortnightly by our department. Data were collected for 12 syntheses of 177Lu-DOTATATE, 8 syntheses of 177Lu-PSMA-617, and 3 syntheses of 177Lu-EDTMP. Mean time required to complete the synthesis was 0.81, 0.65, and 0.58 h, respectively. Mean whole body radiation exposure was 0.023 ± 0.01 mSv, 0.01 ± 0.002 mSv, and 0.002 ± 0.0006 mSv, respectively. Overall mean radiation dose for all the three 177Lu-compounds was 0.014 mSv. Highest exposure was obtained during the synthesis of 177Lu-DOTATATE. Conclusion: Our data suggest that the manual radiolabeling of 177Lu compounds is safe, and the whole body radiation exposure to the involved personnel is well within prescribed limits.

Keywords: Personnel dosimetry, manual radiolabeling, radionuclide therapy

How to cite this article:
Arora G, Mishra R, Kumar P, Yadav M, Ballal S, Bal C, Damle NA. Estimation of whole body radiation exposure to nuclear medicine personnel during synthesis of 177lutetium-labeled radiopharmaceuticals. Indian J Nucl Med 2017;32:89-92

How to cite this URL:
Arora G, Mishra R, Kumar P, Yadav M, Ballal S, Bal C, Damle NA. Estimation of whole body radiation exposure to nuclear medicine personnel during synthesis of 177lutetium-labeled radiopharmaceuticals. Indian J Nucl Med [serial online] 2017 [cited 2019 May 29];32:89-92. Available from: http://www.ijnm.in/text.asp?2017/32/2/89/202245

Introduction

Personnel monitoring is an intergral part of any radiation safety program. Personnel monitoring aims to keep the occupational radiation exposure as low as reasonably achievable (ALARA) and is based on the principle that the benefits of any intentional or planned exposure to radiation should outweigh the resultant detriment that could arise.[1] Safe radiation work practices and permissible radiation exposure limits have been laid by various national and international regulatory authorities.

As per ICRP recommendations 103 (2007), the equivalent radiation dose to personnel should not exceed 20 mSv/year averaged over 5 years, not exceeding 50 mSv in any year.[2] These limits are aimed at keeping the probability of stochastic effects of radiation to the lowest, while avoiding the occurrence of non-stochastic effects altogether. By defination, any person handling radiation and likely to receive an occupational radiation exposure of more than 1 mSv is liable to be monitored.

In nuclear medicine, personnel involved in synthesis of radiopharmaceuticals, dose administration, and/or scan acquisition are most likely to receive radiation exposure. The risk could be even higher while handling therapeutic radiopharmaceuticals. In the present study, we have focussed on the personnel involved in synthesis of radiopharmaceuticals involving Lu-177 that is DOTATATE/DOTANOC, PSMA-617 and EDTMP. The choice of radiopharmaceuticals was based on the fact that these three radiopharmaceuticals are being routinely synthesized at our department, at the All India Institute of Medical Sciences, New Delhi, India.

Over the last decade, Lu-177 has become the radionuclide of choice for various radionuclide therapy procedures owing to its ease of large-scale production in moderate flux reactors, favorable radiation characteristics enabling imaging along with therapy (β-max: 497 keV; γ1: 113 keV; 6.4% and γ2: 208 keV; 11%); and sufficiently long half-life (6.7 days) allowing easy transport to centers far off from a reactor site.[3] These economic, characteristic, and logistic advantages of Lu-177 have become even more significant in developing countries, where affordable therapeutic options are always sought.

Although there is a plethora of literature on the internal dosimetry or patient dosimetry with 177Lu-radiopharmceuticals, there is a lesser literature on the personnel dosimetry, especially those involved in synthesis. 177Lu-DOATATATE/DOTANOC, PSMA-617, and EDTMP can be synthesized in automatic or semi-automatic chemistry modules or by manual methods. Since a manual method is more cost effective than automatic or semi-automatic methods, it is the most widely practiced method in developing countries like India. However, it poses a risk of comparatively higher radiation exposure to the personnel involved. Therefore, the present study aims to monitor the radiation dose levels to personnel during manual synthesis of 177Lu-labeled compounds (DOTATATE/DOTANOC, PSMA-617, and EDTMP) and reviews work practices that may reduce the radiation exposure.


Materials and Methods

Lu-177 as LuCl3 was procured from BRIT, Mumbai, India. A digital pocket dosimeter (MyDose Mini) was obtained from ALOKA. The precursors used in the synthesis of 177Lu-labeled DOTATATE/DOTANOC and PSMA-617 were obtained from ABX GmbH, Germany, and EDTMP kit was obtained from BRIT/Polatom. All other reagents used in labeling were of analytical grade.

Procedure

Synthesis of Lu-177-labeled DOTATATE, PSMA-617, and EDTMP was carried out by designated skilled personnel at the radio-pharmacy laboratory of the Department of Nuclear Medicine, AIIMS, New Delhi, India. These radiopharmaceuticals were routinely synthesized in our department, on fortnightly basis by manual methods. DOTATATE and DOTANOC were labeled alternatively depending on the availability of precursor. The MyDose mini radiation pocket dosimeter was used to measure the radiation exposure. Initially, background radiation of the laboratory, where labeling was carried out, was measured by placing the dosimeter in the laboratory when no radioactive work was being conducted. The background exposure readings were taken at different places around the labeling workbench and mean was calculated.

Personnel were issued a pocket dosimeter prior to the start of labeling procedure. Initial reading of the meter was set at zero every time. Radiation exposure readings recorded in the meter were noted on the completion of labeling process. The total amount of radioactivity handled during labeling and the duration of each labeling procedure were noted.

Statistical Analysis

Descriptive statistic analysis was done for the collected data; and mean, median, standard deviation (SD), and range (minimum to maximum value) were determined. All the readings were expressed as mean ± SD.


Results

A total of 23 readings of radiation exposure were obtained during the labeling of all 177Lu-radiopharmaceuticals put together. [Table 1] shows the number of readings obtained for individual radiopharmaceuticals. Background radiation exposure reading was observed to be zero (for 1 hour) around the labeling workbench when no radioactive work was being conducted.

Table 1: Number of readings of exposure of various radiopharmaceuticals

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The details of radiation dose during labeling of 177Lu-DOTATATE/NOC, PSMA-617, and EDTMP are given in [Table 2], [Table 3], and [Table 4], respectively. [Figure 1] represents the trend of radiation exposure during labeling of the three radiopharmaceuticals.

Table 2: Radiation exposure during the labeling of 177Lu-DOTATATE/NOC

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Table 3: Radiation exposure during the labeling of 177Lu-PSMA-617

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Table 4: Radiation exposure during the labeling of 177Lu-EDTMPS


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Figure 1: Radiation dose of 177Lu labeled DOTATATE/NOC (series 1), PSMA-617 (series 2) and EDTMP (series 3) with the standard error

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The mean radiation dose recorded in 177Lu-DOTATATE/NOC labeling was 0.023 ± 0.01 mSv, 177Lu-PSMA-617 was 0.01±0.002, mSv and 177Lu-EDTMP was 0.002 ± 0.0006 mSv and the mean duration of labeling was 0.81, 0.65, and 0.58 h, respectively. The specific activity of Lu-177 was ~19–22 mCi/µgm in all labeling procedures.

The mean estimated radiation dose rate during the three labeling procedures was 0.03 ± 0.01 mSv/h for DOTATATE/NOC, 0.01 ± 0.003 mSv/h for PSMA-617, and 0.003 ± 0.001 mSv/h for EDTMP. Overall mean radiation dose was 0.014 mSv and duration was 0.72 h.


Discussion

The objective of the study was to evaluate the radiation dose levels to personnel involved in the labeling of 177Lu-labeled radiopharmaceuticals that is DOTATATE/NOC, PSMA-617, and EDTMP. The method of labeling these compounds with Lu-177 may be automated/semi-automated[4],[5] or manual. At our department, we perform routine radiolabeling of these compounds with Lu-177 by a manual method, as it is more cost effective and automated modules are not available to us at present. However, in manual labeling procedures, the radiation safety concerns are higher than that in automated or semi-automated methods.

Labeling of 177Lu-DOTATATE/NOC was performed as per the method described by Das et al.[6] and that of 177Lu-PSMA-617 was performed by the method described by Ahmadzadehfar et al.[7] Automated or semi-automated modules are not available for the labeling of 177Lu-EDTMP, as it is a single step procedure that involves simple addition and incubation of the EDTMP.[8]

Our results suggest that the labeling of 177Lu-DOTATATE/NOC yielded the highest mean radiation dose of 0.023 ± 0.01 mSv, followed by 177Lu-PSMA-617 0.01 ± 0.002 mSv, whereas the dose from the labeling of 177Lu-EDTMP was the lowest 0.002 ± 0.0006 mSv. The reason for the observed trend is the time of radiolabeling, higher the duration of radioactivity handling, higher the radiation exposure. Overall dose trend also follows the same order as can be seen in [Figure 1].

One of the most important factors that may affect the radiation dose to personnel in manual methods of radiolabeling is the skill. Different radiation workers have different levels of proficiency and expertise in the handling of radioisotopes that cause the readings to vary greatly among personnel. In our study, we ensured that every time the same radiation worker was involved in the radiolabeling of a particular compound to minimize such inter-personnel variations. However, intra-personnel variations still exist. Furthermore, to maintain uniformity of measurements and minimize the errors, the pocket dosimeter assigned to particular personnel during labeling was kept the same. It was also ensured that through out the observation period (labeling process), the personnel do not carry out any other radiation work or go to any other radiation area that might yield erroneously high reading on the dosimeter.

Other factors that might affect radiation dose are the duration and amount of radioactivity handled during the labeling procedure. Both, radioactivity and mean duration are highest for DOTATATE/NOC (896 mCi; 0.81 h), followed by PSMA-617 (190 mCi; 0.65 h), and EDTMP (57 mCi; 0.58 h) in our study. This explains the trend of radiation dose for the three procedures.

Overall mean radiation dose for all the three 177Lu-compounds was 0.014 mSv. Our department has a high throughput of patients, and synthesis of 177Lu-compounds is performed once every fortnight, provided there is timely availability of Lu-177 and precursors. Assuming 24 such synthesis every year, the total mean dose to the personnel involved will be ~0.34 mSv. This dose level is far less than the stipulated limit of 20 mSv. Even if in future the synthesis rate increases to once per day and the same radiopharmacist is involved in synthesis, the dose will be ~5.26 mSv. The background activity in the radiolabelling laboratory returned to that existed pre-labeling, that is, zero (for 1 hour) after proper disposal of radioactive vials, syringes, absorbent sheets, gloves, and other contaminated waste. These things were properly sealed, labeled, and stored in a waste disposal room for decay. The reading of the TLD badge of the personnel involved was also within prescribed limits, that is, 0.9 mSv for chest badge for 1 year. It should be noted that this reading includes the radiation expsure to the presonnel from other sources as well apart from the radiolabeling procedures mentioned in this study as the personnel was involved in other departmental work also. This shows that even the manual radio-labeling methods of Lu-177 compounds are safe, provided safe work practices are followed.

The dose can be further reduced by involving staff well trained in good radio-pharmacy practices and radiation safety. Though the procedures are safe even if a single trained staff member conducts all the synthesis, it would be preferable to involve minimum two trained personnel to share and further reduce the radiation burden. The regular use of radiation monitoring devices such as the pocket dosimeters and TLD badges should be encouraged, and radiation surveys should be routinely conducted.

The study was conducted over a period of 6 months and various logistic reasons such as unexpected delay in delivery of Lu-177, or precursors sometimes restricted the regular synthesis of 177Lu-compounds at our department. Hence, not much data points could be collected that is a major limitation of the study. Furthermore, due to unavailability of automated/semi-automated chemistry modules at our department a direct comparison was not possible. However, despite a less number of observations, the study is significant as there are only few similar studies on radiation dose levels to personnel involved in Lu-177 radio-labeling.


Conclusion

Our data suggest that the manual radio-labeling of 177Lu-compounds is safe and the whole body radiation exposure to the involved personnel is well within the prescribed limits of ICRP, i.e., 20 mSv/year (averaged over 5 years). However, the exposure can further be reduced using semi-automated and automated modules, wherever possible.

The information comes from:
http://www.ijnm.in/article.asp?issn=0972-3919;year=2017;volume=32;issue=2;spage=89;epage=92;aulast=Arora;type=3