Interval Changes in PSMA PET/CT During Radium-223 Therapy for Metastatic Bone Disease from Castration-Resistant Prostate Cancer

Stephan Probst,Anders Bjartell,Aseem Anand,Tayna Skamene,Cristiano Ferrario 대한핵의학회 2022 핵의학 분자영상 Vol.56 No.4

Background Radium-223, an alpha-emitting therapeutic radiopharmaceutical, prolongs overall survival (OS) in patients with symptomatic bone-predominant metastatic castration-resistant prostate cancer (mCRPC). PSMA PET/CT is a molecular imaging tool for whole-body imaging of prostate cancer and may inform on the mechanisms of radium-223 activity and treatment resistance in mCRPC patients. Methods In an open-label, single-arm, prospective trial, we enrolled patients with bone-predominant mCRPC to undergo baseline PSMA PET/CT, 6 cycles of radium-223, and post-therapy PSMA PET/CT. We assessed the relationship between multiple parameters of interval change on PSMA PET/CT on aPROMISE PSMA automated analysis and a human reader, and laboratory measurements. Results Fourteen patients were enrolled and 9 patients completed both protocol-defined PSMA PET/CT. Of the 9 evaluable patients, 1 (11%) had a complete response and 8 (89%) had PSMA PET progressive disease. All patients showed decreases in PSMA uptake in some disease sites evident on the baseline scan. The change in overall burden of disease on PSMA PET was more strongly correlated with changes in PSA (ρ = 0.95) than ALP (ρ = 0.62). Progression in bone was a common finding on post-treatment PSMA PET/CT. Conclusion PSMA PET was able to assess response in individual lesions during radium-223 therapy in mCRPC patients. PSMA PET responses in previously established disease sites were universal, but most patients also showed overall PSMA PET progression during 6 cycles of radium-223. Given high correlation with changes in PSA, PSMA PET may be of limited value in follow-up during or after radium-223 in bone-predominant mCRPC.

Outcomes and Factors Associated with Completion of Radium-223 Therapy

Richard F. Liu,Lamin Juwara,Cristiano Ferrario,Stephan M. Probst 대한핵의학회 2022 핵의학 분자영상 Vol.56 No.5

Purpose Radium-223 has been demonstrated in clinical trials to improve survival in castration-resistant prostate cancer (CRPC) patients with bone metastases. However, its performance in routine use remains to be fully characterized. This study aims to describe patient outcomes in the real world as well as identify factors associated with completion of the 6-dose regimen and alkaline phosphatase (ALP) response. Methods Thirty-six patients who received at least one dose of radium-223 at the Jewish General Hospital in Montréal, Canada, were analysed in a retrospective manner. Using logistic regression, the primary analysis aimed to identify factors associated with treatment completion, and the secondary analysis aimed to identify factors associated with ALP response. Results Twenty-one out of 36 patients received all 6 doses of radium-223. Fifteen patients had an ALP response, defined as a 30% decrease in ALP from baseline values. On primary analysis, baseline ALP > 120 U/L and prostate-specific antigen (PSA) > 50 μg/L were significantly associated with lower therapy completion rates (OR = 0.10, p = 0.004; OR = 0.18, p = 0.022 respectively). On adjustment for confounders, only ALP remained significant (OR = 0.14, p = 0.021). Clinical disease progression was the most common reason for treatment non-completion, and it was also associated with elevated baseline ALP (OR = 6.00, p = 0.044). On secondary analysis, previous chemotherapy for CRPC was a negative predictor of ALP response (OR = 0.15, p = 0.034). Conclusion Elevated baseline ALP and PSA were associated with a lower rate of radium-223 regimen completion; receiving chemotherapy for CRPC prior to radium-223 was associated with a lower rate of ALP response.

Changes in Skeletal Tumor Activity on 18F-choline PET/CT in Patients Receiving 223Radium Radionuclide Therapy for Metastatic Prostate Cancer

Kyle S. Miyazaki,Yu Kuang,Sandi A. Kwee 대한핵의학회 2015 핵의학 분자영상 Vol.49 No.2

Radium-223 dichloride is an alpha-emitting radiopharmaceutical shown to prolong survival in patients with castrate-resistant prostate cancer (CRPC) and symptomatic skeletal metastases. This report describes in two patients the acute changes in bone metastatic activity detected by F-18 choline PET/CT imaging midway during treatment with radium-223 dichloride. In addition to visual and standardized uptake value analysis, changes in the whole-body tumor burden were quantified by measuring the difference in net metabolically active tumor volume (MATV) and total lesion activity (TLA) between pre- and mid-treatment PET scans. After the third dose of radium-223 dichloride, near-total disappearance of abnormal skeletal activity was observed in one case (net MATV change from 260.7 to 0.8 cc; net TLA change from 510.7 to 2.1), while a heterogeneous tumor response was observed in the other (net MATV change from 272.2 to 241.3 cc; net TLA change from 987.1 to 779.4). Corresponding normalization and persistent elevation in serum alkaline phosphatase levels were observed in these cases, respectively. Further research is needed to determine the predictive value of serial F-18 choline PET/CT imaging in patients receiving radium-223 dichloride for CRPC.

한일병원에서 방사선조사 ( Cs137원격조사,Radium강내조사 ) 에 의한 자궁경암 치료 ( 제 2보 )

신웅호(WH Shin),강영호(YH Kang),옹상길(SK Ong) 대한산부인과학회 1966 Obstetrics & Gynecology Science Vol.9 No.11

In the first section(basic section) of this report, the physical characteristics and biologic effects of Cs137 in comparison with Co60 and X-ray as the external irradiation therapy, and the advantages and the method of dosage calculation in use of TAO(Tasaki, Arai, Otachi) applicator, the afterloading technic of Ra, as the internal irradiation therapy were dicussed. Cs137 and Co60 are more excellent in their therapeutic effects than conventional x-ray. Cs137 has longer half-life, less penumbra, ease in protection, and costs low for its installation, but has lower energy level with less depth dose and dose rate. In calculation of Ra dosage, two methods were adopted instead of mg. hr or mC. hr which were less valuable for accurate biologic effects. Unit of R(Roentgen) in bilateral points A&points B was calculated. In the second section(clinical section), 167 cases from 181 cases who were admitted and treated for the invasive cancer of the uterine cervix since July, 1962 till June, 1966 were studied about the clinical therapeutic effects after the irradiation therapy. Four cases with radical operation only and 10 cases with chemotherapy were excluded in this study. The 167 cases were divided into group Ⅰ(119 cases) in which subgroup A treated with Cs137 therapy only and subgroup B with Ra and Cs137 therapy were include, and group Ⅱ(48 cases) in which subgroup C(46 cases) with Cs137 therapy after radical operation and subgroup D(2 cases) with radical operation after the irradiation therapy were included. The following results were obtained; 1. The local lesions of the cervix were improved in about 80 per cent of cases. And the effect was better in subgroup B than in subgroup A. 2. The size of induration from the parametrial invasion was also decreased in about 70 per cent of cases. 3. Incidence of metastasis to the pelvic lymph nodes was 14.3 per cent in 28 cases of stage Ⅰ and 38.8 per cent in 18 cases of stage Ⅱ. 4. Recurrences of the cervical cancer were detected in 23 cases, mostly within one year after radiation therapy. Most prevalent sites were the vaginal wall (16 cases) and pelvic cavity (12 cases). Eleven cases from them expired within one year and twelve cases were lost. 5. As radiation sickness, nausea, general wekness, anorexia, and heakache were most common. And they were most severe in 10th to 15th day after beginning of radiation therapy and then gradually subsided, 6. Erythema and/or dark pigmentation of the skin were common, but excoriation (5.4%), bulla(3.2%), and ulceration(3.2%) were rare 7. Other common complications during radiation therapy were disorders of the rectum (22 cases) and bladder disturbances (11 cases). 8. Survival rate: (1) In group I: Two years after completion of radiation therapy, 70 cases (46.2%) from 149 cases were lost. Three years after completion of radiation therapy, 65 cases (58.6%) from 111 cases were lost. And their survival rates were uncertain. (2) In subgroup C (with Cs137 therapy after radical operation): Two years survival rate in 44 cases, two years after completion of radiation therapy (7 case were lost), was 84.6 per cent in the first stage and 55.6 per cent in the second stage. Three years survival rate in 33 cases, three years after completion of radiation therapy (10 cases were lost), was 63.2 per cent in the first stage and 50.0 per cent in the second stage.

Acute Promyelocytic Leukemia After Radium-223 Exposure for Prostate Cancer in a Chemotherapy-Naïve Patient

Perrone Salvatore,Ortu La Barbera Elettra,Ottone Tiziana,Capriata Marcello,Passucci Mauro,Filippi Luca,Bagni Oreste,Voso Maria Teresa,Cimino Giuseppe 대한핵의학회 2020 핵의학 분자영상 Vol.54 No.5

223Ra-dichloride is a bone-seeking targeted alpha (α)-emitting approved for bonemetastases in prostate cancer. Here, we report a case of therapy-related acute promyelocytic leukemia (t-APL) following administration of 223Ra, showing some evidence of a causative relationship. A patient with metastatic prostate cancer received therapy with 223Ra, with 6 injections of the radiopharmaceutical at a standard dose of 55 kBq/kg at 4-week intervals for a cumulative administered activity of 26.3MBq. PET/CT with 18F-methylcholine repeated 1 month after the conclusion of 223Ra was negative. After 8 months, he developed pancytopenia and we made a diagnosis of therapy-related acute promyelocytic leukemia (t-APL). We then studied the genomic locations of the breakpoints in the PML and RARA genes, which were at nucleotide positions 1708-09 of PML intron 3, respectively, outside the previously reported Topo II-associated hotspot region. t-APL was cured with all-trans-retinoic acid (ATRA) and arsenic trioxide. The type of PML/RARA rearrangement we identified, in absence of other myelotoxic treatments, is suggestive of a possible direct causal relationship with exposure to 223Ra and warrants further investigations.

Current Status and Growth of Nuclear Theranostics in Singapore

Hian Liang Huang,Aaron Kian Ti Tong,Sue Ping Thang,Sean Xuexian Yan,Winnie Wing Chuen Lam,Kelvin Siu Hoong Loke,Charlene Yu Lin Tang,Lenith Tai Jit Cheng,Gideon Su Kai Ooi,Han Chung Low,Butch Maulion 대한핵의학회 2019 핵의학 분자영상 Vol.53 No.2

The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of ‘personalised’ medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore.We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy.We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.

감마선 분광법을 이용한 지하수 중의 ²²⁶Ra 분석

서범경,이길용,윤윤열,이근우,Seo, Bum-Kyoung,Lee, Kil-Yong,Yoon, Yoon-Yeol,Lee, Kune-Woo 한국분석과학회 2003 분석과학 Vol.16 No.1

시료 전처리가 필요 없는 감마선 분광분석법을 이용하여 지하수 중의 라듐 ($^{226}Ra$) 분석을 위한 측정법을 확립하였다. 방사평형된 딸핵종을 이용한 라듐의 분석 시 가장 문제가 되는 대기 중 라돈 딸핵종에 의한 바탕계수는 측정함 내부로 질소가스를 흘려주므로써 해결하였고, 라듐과 그 딸핵종들 사이의 방사평형 과정에서 생성된 라돈가스의 용기 외부로의 누출은 밀폐된 알루미늄 용기를 사용함으로써 방지할 수 있었다. 또한 측정용기 내부의 공기층에 의한 방사능 변화정도를 조사하기 위하여 임의로 공기층을 만들어 측정한 결과, 물 속에 녹은 라돈의 공기층으로의 발산에 의한 방사능 변화정도는 통상적인 측정오차인 5% 범위 이내였다. 측정 시 검출기 주위로 질소가스를 흘려줌으로서 대기 중 라돈 딸핵종에 의한 간섭을 제거하였고, 검출하한값을 0.02 Bq/L로 낮출 수 있었다. 이는 최근 US Environmental Protection Agency (EPA)에 의하여 제안된 지하수 중의$^{226}Ra$ Maximum Contaminant Level (MCL)인 0.74 Bq/L보다 충분히 작은 값으로서 감마선 분광법을 이용하여 지하수 중의 라듐을 방사능 농도를 정확히 결정할 수 있다는 것을 확인하였다. The measurement of radium ($^{226}Ra$) in the groundwater was established using ${\gamma}$-ray spectroscopy without sample preparation. The background interference by air borne radon daughter nuclides was reduced by $N_2$ gas flow into the counting chamber. Leakage of radon gas produced in the radioactive equilibrium with radium and its daughter nuclides was prevented by use of the air-tighted aluminium container. We investigated the effect of air layer in the counting container. Radioactivity variation due to emanation of radon into the air layer was within the counting error range 5%. When the nitrogen gas was flowed around the detector, peak counts of ${\gamma}$-rays from the daughters of airborne radon was decreased and detection limit was decreased to 0.02 Bq/L. The detection limit of detector was lower than 0.74 Bq/L, the $^{226}Ra$ Maximum Contaminant Level (MCL) in the groundwater proposed by US Environmental Protection Agency (EPA). It was confirmed that $^{226}Ra$ radioactivity in the groundwater could be determined by the ${\gamma}$-ray spectroscopy.

액체섬광계수기를 이용한 토양 중 226Ra 분석 방법 연구

정윤희,김현철,정근호,강문자 한국분석과학회 2016 분석과학 Vol.29 No.2

This study presented an analytical method for detecting radium in soils using a liquid scintillation counter (LSC). The isotope 226Ra was extracted from soil using the fusion method and then separated from interfering radionuclides using the precipitation method. Radium was coprecipitated as sulfate salts with barium (Ba) and then converted into Ba(Ra)CO3, which is soluble in an acidic solution. The isotope 222Rn, the decay progeny of 226Ra, was trapped in a water immiscible cocktail and analyzed by LSC. The pulse shape analysis (PSA) level was estimated using 90Sr and 226Ra standard solutions. The figure of merit was the highest at PSA 80, while the alpha spillover was the lowest at PSA 80. The counting efficiency was 243 ± 2% in a glass vial. This analytical method was verified with International Atomic Energy Agency (IAEA) reference materials, including IAEA-312, IAEA-314, and IAEA-315. The recovery ranged from 60–82%, while the relative bias between the measured value and the recommended value was less than 10%. The minimum detectable activity was 2.1 Bq kg−1 with dry mass 1 g, the background count rate of 0.02 cpm, the recovery rate of 70% and counting time of 30 min.

Activity concentrations and radiological hazard assessments of ²²⁶Ra, ²³²Th, ⁴⁰K, and ¹³⁷Cs in soil samples obtained from the Dongnam Institute of Radiological & Medical Science, Korea

Jieun Lee,HyoJin Kim,Yong Uk Kye,Dong Yeon Lee,Wol Soon Jo,Chang Geun Lee,Jeung Kee Kim,Jeong-Hwa Baek,Yeong-Rok Kang Korean Nuclear Society 2023 Nuclear Engineering and Technology Vol.55 No.7

The radioactivity concentration of environmental radionuclides was analyzed for soil and sand at eight locations within a radius of 255 m centered on the Dongnam Institute of Radiological & Medical Science (DIRAMS), Korea. The average activity concentrations of ⁴⁰K, ¹³⁷Cs, ²²⁶Ra, and ²³²Th were 661.1 Bq/kg-dry, 0.9 Bq/kg-dry, 21.9 Bq/kg-dry, and 11.1 Bq/kg-dry, respectively. The activity of ⁴⁰K and ¹³⁷Cs was lower than the 3-year (2017-2019) average reported by the Korea Institute of Nuclear Safety, respectively. Due to the nature of granite-rich soil, the radioactivity of ⁴⁰K was 0.6-fold higher than in other countries, while ¹³⁷Cs was in the normal fluctuation range (15-30 Bq/kg-dry) of the concentration of radioactive fallout from nuclear tests. The activity of ²²⁶Ra and ²³²Th was lower than in Korean soils reported by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). The average activity concentrations of ²³²Th and ⁴⁰K for the soil and sand samples from DIRAMS were within the range specified by UNSCEAR in 2000. The radium equivalent activity and internal and external hazard index values were below the recommended limits (1 mSv/y). These radionuclide concentration (²²⁶Ra, ²³²Th, ⁴⁰K, and ¹³⁷Cs) data can be used for regional environmental monitoring and ecological impact assessments of nuclear power plant accidents.

Reevaluation of mixing among multiple water masses in the shelf: An example from the East China Sea

Zhang, L.,Liu, Z.,Zhang, J.,Hong, G.H.,Park, Y.,Zhang, H.F. Pergamon Press ; Elsevier Science Ltd 2007 Continental shelf research Vol.27 No.15

East China Sea (ECS) is bounded by the continent where the fourth largest river of Changjiang discharges large amounts of freshwater to the west and by the Kuroshio in the East and connected to the South China Sea via Taiwan Strait, therefore water characteristics are very complex and undergo great seasonal changes. The dominant source waters in the ECS are found to be Kuroshio Surface Water (KSW), Kuroshio Sub-surface Water (KSSW), Changjiang Diluted Water (CDW), and Taiwan Strait Warm Water (TSWW). Optimum multiparameter analysis (OMP) using temperature, salinity and <SUP>226</SUP>Ra were applied to quantify the contribution of individual source water to the surface water of the ECS in summer. The successful application of radium isotope in OMP analysis demonstrates the usefulness of <SUP>226</SUP>Ra in the discrimination of mixing among multiple water sources. In 1987, one interesting phenomenon was that the KSSW entered the surface with the upwelling at the margin of continental shelf, and affected the coastal water obviously. In 1999, the TSWW extended northward continuously up to the Changjiang Estuary.