• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1313-1320
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• 2014

Introduction: Although most prostate cancers initially respond to castration with luteinizing hormonereleasing analogues or bilateral orchiectomy, progression eventually occurs. Based on the exciting results of several randomized controlled trials (RCTs), it seems that patients with metastatic castration-resistant prostate cancer (mCRPC) might benefit more from treatment withabiraterone. Therefore we conducted a systematic review to evaluate the efficacy and toxicity of abiraterone in the treatment of mCRPC. Methods: Literature was searched from Embase, PubMed, Web of Science, and Cochrane Library up to July, 2013. Quality of the study was evaluated according to the Cochrane's risk of bias of randomized controlled trial (RCT) tool, then the Grading of Recommendations Assessment, Development and Evaluation (GRADE) System was used to rate the level of evidence. Stata 12.0 was used for statistical analysis. Summary data from RCTs comparing abiraterone plus prednisone versus placebo plus prednisone for mCRPC were meta-analyzed. Pooled hazard ratios (HRs) for overall survival (OS), radiographic progression-free survival (RPFS) and time to PSA progression (TTPP); Pooled risk ratios (RR) for PSA response rate, objective response rate and adverse event were calculated. Results: Ten trials were included in the systematic review; Data of 2,283 patients (1,343 abiraterone; 940 placebo) from two phase 3 trials: COU-AA-301 and COU-AA-302 were meta-analyzed. Compared with placebo, abiraterone significantly prolonged OS (HR, 0.74; 95% confidence interval [CI], 0.66 to 0.84), RPFS (HR, 0.59; 95% CI, 0.48 to 0.74) and time to PSA progression (HR, 0.55; 95% CI, 0.43 to 0.70); it also significantly increased PSA response rate (RR, 3.63; 95% CI, 1.72 to 7.65) and objective response rate (RR, 3.05; 95% CI, 1.51 to 6.15). This meta-analysis suggested that the adverse events caused by abiraterone are acceptable and can be controlled. Conclutios: Abiraterone significantly prolonged OS, RPFS and time to progression patients with mCRPC, regardless of prior chemotherapy or whether chemotherapy-na$\ddot{i}$ve, and no unexpected toxicity was evident. Abiraterone can serve as a new standard therapy for mCRPC.

• Korean Journal of Radiology
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• 제25권2호
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• pp.179-188
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• 2024

Objective: ¹⁷⁷Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [¹⁷⁷Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods: Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I study with activity escalation design of single administration of [¹⁷⁷Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [¹⁷⁷Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organand tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1. Results: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq. Conclusion: [¹⁷⁷Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1285-1290
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• 2014

The aim was to determine whether ultrasound targeted microbubble destruction (UTMD) promotes dual targeting of HSP72 and HSC70 for therapy of castration-resistant prostate cancer (CRPC), to improve the specific and efficient delivery of siRNA, to induce tumor cell specific apoptosis, and to find new therapeutic targets specific of CRPC.VCaP cells were transfected with siRNA oligonucleotides. HSP70, HSP90 and cleaved caspase-3 expression were determined by real-time quantitative polymerase chain reaction and Western blotting. Apoptosis and transfection efficiency were assessed by flow cytometry. Cell viability assays were used to evaluate safety. We found HSP72, HSC70 and HSP90 expression to be absent or weak in normal prostate epithelial cells (RWPE-1), but uniformly strong in prostate cancerous cells (VCaP). UTMD combined with dual targeting of HSP72 and HSC70 siRNA improve the efficiency of transfection, cell uptake of siRNA, downregulation of HSP70 and HSP90 expression in VCaP cells at the mRNA and protein level, and induction of extensive tumor-specific apoptosis. Cell counting kit-8 assays showed decreased cellular viability in the HSP72/HSC70-siRNA silenced group. These results suggest that the combination of UTMD with dual targeting HSP70 therapy for PCa may be most efficacious, providng a novel, reliable, non-invasive, safe targeted approach to improve the specific and efficient delivery of siRNA, and achieve maximal effects.

• 핵의학기술
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• 제20권1호
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• pp.28-31
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• 2016

전립선암은 세계적으로 남성에게 발생하는 가장 흔한 암이며, 암 관련 이환 및 사망의 주요 원인 중 하나이다. 전립선 암세포는 안드로겐에 의해 자극되며 안드로겐 수용체에 결합하여 활성화된다. 안드로겐 수용체는 전사인자로 작용하며 세포주기, 증식 및 분화를 조절한다. 안드로겐 수용체 신호 차단은 전립선암 치료의 특징이다. 전립선암에서 통증은 빈번하게 일어나는 관련 증상으로 환자의 삶의 질 악화의 주요 원인 중 하나이다. 주사용 $^{223}Ra-Dichloride$는 28 Mev 알파 방사선을 방출하여 골 전이가 있는 거세저항성 전립선암(Castration-Resistant Prostate Cancer)의 치료에 이용되고 있다. $^{223}Ra$은 체내 반감기가 11.4 일, 100 마이크로미터 이하 범위의 높은 선 에너지 전달(LET) 알파선을 방출하므로 매우 국소적인 방사선 영역을 생성시키는데 사용할 수 있다. 골격 전이와 같은 표적조직에 알파선을 위치하게 되면 베타선보다 더 국소적 용적으로 방사선을 전달하여 주위의 정상조직에 대한 노출을 줄인다. 하지만 $^{223}Ra-Dichloride$는 알파선 이외에 붕괴 과정에서 3.6%의 베타선과 1.1%의 감마선 (80, 156, 270 keV)을 방출한다. 본 연구는 $^{223}Ra-Dichloride$ 치료 시 사용되는 방사능양 3.5 MBq과 $^{99m}Tc-MDP$를 사용하여 Bone scan 검사 시 사용되는 방사능양 740 MBq을 사용하여 감마선에 대한 외부 방사선량을 평가해보고자 하였다. 최대 외부 방사선량은 $D({\infty})=34.6{\tau}Q_0Tp(0.25)$(${\tau}$:감마상수, $Q_0$:초기방사능양, Tp:물리적 반감기) 식을 이용하여 산출하였으며, 실제로 vial에서 방출되는 감마선을 1m의 거리에서 survey meter를 이용하여 15회 외부 방사선량률을 측정하였다. Health physics(2012)에서 제공하는 $^{223}Ra-Dichloride$과 $^{99m}Tc-MDP$의 1m 거리에서의 감마상수의 값은 각각 0.0469, 0.0215, 실제로 사용되는 방사능양 3.5 MBq, 740 MBq, 반감기 11.4일, 6시간을 기준으로 산출된 외부 방사선량은 $^{223}Ra-Dichloride$은 $16{\mu}Sy$, $^{99m}Tc-MDP$은 $34{\mu}Sy$의 값을 보였다. 실제로 vial에서 1 m 거리에서 방출되는 외부 방사선량율은 평균 $^{223}Ra-Dichloride$는 ${\mu}Sy/h$, $^{99m}Tc-MDP$은 $18{\mu}Sy/h$ 값이 측정값을 보였다. 감마상수 값은 $^{223}Ra-Dichloride$이 $^{99m}Tc-MDP$에 비해 높은 값을 나타내지만 실제로 사용되는 방사능의 양을 고려한 최대 외부 방사선량은 $^{223}Ra-Dichloride$이 $^{99m}Tc-MDP$보다 낮은 최대 외부 방사선량 값이 산출되었으며, 실제로 측정한 외부 방사선량율도 작은 값을 보여 $^{223}Ra-Dichloride$을 이용한 치료시 감마선에 대한 외부 방사선량은 매우 작음을 알 수 있었다. $^{223}Ra-Dichloride$은 골 전이가 있는 거세저항성 전립선암(Castration-Resistant Prostate Cancer) 환자들에게 유용한 치료제라고 사료된다.