• Asian Pacific Journal of Cancer Prevention
• /
• 제15권8호
• /
• pp.3645-3649
• /
• 2014

The aim of this study was to evaluate the efficacy of third-line combined androgen blockade (CAB) therapy for castration-resistant prostate cancer that relapsed after primary and second-line CAB. We retrospectively reviewed the medical records of 52 patients who received first-, second-, and third-line CAB therapy (medical or surgical castration, plus steroidal antiandrogen of chlormadinone acetate, or nonsteroidal antiandrogen of flutamide or bicalutamide). For cumulative analysis, we searched the PubMed database and identified a total of 50 cases published in English. Including our cases, this provided a total of 102 cases for analysis. In our study cohort, 11 cases (21.2%) achieved more than 50% reduction of serum prostate-specific antigen (PSA) on initiation of third-line CAB. We found that third-line CAB with nonsteroidal antiandrogen after second-line CAB with steroidal antiandrogen exhibited favorable results, with a positive response in six of 13 patients (46.2%). Cumulative analysis findings were comparable. Regarding the timing of third-line CAB administration, 15 patients had started at a PSA equal to or less than 4.0 ng/ml, and eight of them (53.3%) showed a positive response to treatment, compared to only three of 37 patients (8.1%) whose PSA at the initiation of third-line therapy was higher than 4.0 ng/ml (p<0.001). We conclude that third-line CAB with nonsteroidal antiandrogen would be particularly useful for patients whose cancer progressed after second-line CAB with steroidal antiandrogen. The timing of treatment seems to be important because the higher the PSA at the start of third-line therapy, the lower the PSA response rate.

• 대한비뇨기종양학회지
• /
• 제16권3호
• /
• pp.126-134
• /
• 2018

Purpose: The purpose of this study is to compare the radiation therapy (RT) and radical prostatectomy (RP) of high-risk or locally advanced prostate cancer (PC) patients after neoadjuvant hormonal therapy (NHT). Materials and Methods: This retrospective study evaluated patients underwent RT (42 patients) or RP (152 patients) after NHT at a single center during 2003-2014. Times to biochemical recurrence (BCR), pelvic local recurrence (PLR), metastasis, clinical painful symptom progression (CPSP), castration-resistant PC (CRPC), and overall survival were compared between the RT and RP groups, after adjustment for TN stage, using the Kaplan-Meier method and log-rank test. Results: Significant inter-group differences were observed for age, Gleason score, initial PSA, and clinical and pathological T stages (all p<0.05). During a median follow-up of 71.7 months, the overall incidences of BCR, PLR, metastasis, CPSP, CRPC, and death were 49.5%, 16.5%, 8.3%, 7.7%, 7.7%, and 17.5%, respectively. The median times to BCR were 100 months for RT and 36.2 months for RP (p=0.004), although the median times were not reached for the other outcomes (all p>0.05). The independent predictor of CPSP was RP (hazard ratio, 0.291; p=0.013). Conclusions: Despite significantly different baseline parameters, RP provided better CPSP-free survival than RT among patients with localized high-risk or locally advanced PC.

• Korean Journal of Radiology
• /
• 제24권6호
• /
• pp.574-589
• /
• 2023

Radiopharmaceuticals targeting prostate-specific membrane antigens (PSMA) are essential for the diagnosis, evaluation, and treatment of prostate cancer (PCa), particularly metastatic castration-resistant PCa, for which conventional treatment is ineffective. These molecular probes include [⁶⁸Ga]PSMA, [¹⁸F]PSMA, [Al¹⁸F]PSMA, [^99mTc]PSMA, and [⁸⁹Zr]PSMA, which are widely used for diagnosis, and [¹⁷⁷Lu]PSMA and [²²⁵Ac]PSMA, which are used for treatment. There are also new types of radiopharmaceuticals. Due to the differentiation and heterogeneity of tumor cells, a subtype of PCa with an extremely poor prognosis, referred to as neuroendocrine prostate cancer (NEPC), has emerged, and its diagnosis and treatment present great challenges. To improve the detection rate of NEPC and prolong patient survival, many researchers have investigated the use of relevant radiopharmaceuticals as targeted molecular probes for the detection and treatment of NEPC lesions, including DOTA-TOC and DOTA-TATE for somatostatin receptors, 4A06 for CUB domain-containing protein 1, and FDG. This review focused on the specific molecular targets and various radionuclides that have been developed for PCa in recent years, including those mentioned above and several others, and aimed to provide valuable up-to-date information and research ideas for future studies.

• Korean Journal of Radiology
• /
• 제25권2호
• /
• pp.179-188
• /
• 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
• /
• 제15권3호
• /
• pp.1285-1290
• /
• 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
• /
• 제20권1호
• /
• pp.28-31
• /
• 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.