[223Ra] RaCl2 nanomicelles showed potent effect against osteosarcoma: targeted alpha therapy in the nanotechnology era.

The treatment of bone metastatsis as primary bone cancer itself is still a challenge. The use od radium dichloride ([223Ra] RaCl2) has emerged in the last few years as one of the best treatment choice for bone cancer, with especial focus in bone metastasis. The alpha-emitter radiopharmaceutical has showed potent and efficient results in several clinical trials. In this study we have formulated radium dichloride ([223Ra] RaCl2) nanomicelles in order to evaluate and compare with pure radium dichloride ([223Ra] RaCl2). The results showed that nanomicelles at the same dose had a superior effect (20% higher efficient) when compared with pure radium dichloride ([223Ra] RaCl2). The results corroborated the effectiveness of the nanosystem validating the application of nanotechnology in alpha-radiotherapy with radium dichloride ([223Ra] RaCl2).

Ra-223 and Ethinylestradiol Combination Therapy in Castration-resistant Prostate Cancer.

BACKGROUND/AIM: Ra-223 is a therapeutic agent for bone metastatic castration-resistant prostate cancer (mCRPC). We examined the efficacy of a treatment method using Ra-223 together with ethinylestradiol (EE). PATIENTS AND METHODS: Patients who received Ra-223 three or more times were included and two groups (with or without EE) were compared retrospectively. RESULTS: Eighteen patients were treated with Ra-223 and EE concomitantly (EstRadium therapy) and 13 patients were treated with Ra-223 alone or Ra-223 and agents other than EE (non-EstRadium therapy). The number of patients with decreased serum prostate-specific antigen level was significantly higher in the EstRadium therapy group than in the non-EstRadium therapy group (p=0.029). CONCLUSION: The combination of Ra-223 and EE, compared to Ra-223 alone, is an effective treatment option for bone mCRPC patients, in terms of PSA response.

Association of Chemotherapy, Enzalutamide, Abiraterone, and Radium 223 With Cognitive Function in Older Men With Metastatic Castration-Resistant Prostate Cancer.

Importance: Older adults are at greater risk of cognitive decline with various oncologic therapies. Some commonly used therapies for advanced prostate cancer, such as enzalutamide, have been linked to cognitive impairment, but published data are scarce, come from single-group studies, or focus on self-reported cognition. Objective: To longitudinally examine the association between cognitive function and docetaxel (chemotherapy), abiraterone, enzalutamide, and radium Ra 223 dichloride (radium 223) in older men with metastatic castration-resistant prostate cancer. Design, Setting, and Participants: A multicenter, prospective, observational cohort study was conducted across 4 academic cancer centers in Ontario, Canada. A consecutive sample of 155 men age 65 years or older with metastatic castration-resistant prostate cancer starting any treatment with docetaxel, abiraterone acetate, enzalutamide, or radium Ra 223 dichloride (radium 223) were enrolled between July 1, 2015, and December 31, 2019. Exposures: First-line chemotherapy (docetaxel), abiraterone, enzalutamide, or radium 223. Main Outcomes and Measures: Cognitive function was measured at baseline and end of treatment using the Montreal Cognitive Assessment, the Trail Making Test part A, and the Trail Making Test part B to assess global cognition, attention, and executive function, respectively. Absolute changes in scores over time were analyzed using univariate and multivariable linear regression, and the percentages of individuals with a decline of 1.5 SDs in each domain were calculated. Results: A total of 155 men starting treatment with docetaxel (n = 51) (mean [SD] age, 73.5 [6.2] years; 34 [66.7%] with some postsecondary education), abiraterone (n = 29) (mean [SD] age, 76.2 [7.2] years; 18 [62.1%] with some postsecondary education), enzalutamide (n = 54) (mean [SD] age, 75.7 [7.4] years; 33 [61.1%] with some postsecondary education), and radium 223 (n = 21) (mean [SD] age, 76.4 [7.2] years; 17 [81.0%] with some postsecondary education) were included. Most patients had stable cognition or slight improvements during treatment. A cognitive decline of 1.5 SDs or more was observed in 0% to 6.5% of patients on each measure of cognitive function (eg, 3 of 46 patients [6.5%; 95% CI, 2.2%-17.5%] in the group receiving chemotherapy [docetaxel] had a decline of 1.5 SDs for Trails A and Trails B). Although patients taking enzalutamide had numerically larger declines than those taking abiraterone, differences were small and clinically unimportant. Conclusions and Relevance: These findings suggest that most older men do not experience significant cognitive decline in attention, executive function, and global cognition while undergoing treatment for advanced prostate cancer regardless of the treatment used.

Calculation of radium-223 and actinium-225 α-emitter radiopharmaceuticals dose rates in treatment of metastatic castration-resistant prostate cancer.

AIM OF STUDY: There is limited information regarding the α-emitter radiopharmaceuticals dose calculation used in the setting of men with prostate cancer (PCa). The present study investigates the α-emitter radiopharmaceuticals absorbed dose distribution in the body organs. MATERIALS AND METHODS: The α-emitter radiopharmaceuticals dose coefficient and absorbed doses biokinetics distribution, which are used for the treatment of PCa in all over the world, were performed using the "Internal Dose Assessed by Computer" (IDAC-Dose 2.1) program. The results of absorbed dose distribution in any organ of the body, were compared in studied α-emitter radiopharmaceuticals. RESULTS: The absorbed dose value of 223Ra radiopharmaceutical in the prostate organ was evaluated 9.47E-9 Gy/Bq. The maximum and minimum absorbed doses due to biokinetics distribution of 223Ra were found in the thymus (9.53E-8 Gy/Bq) and eye lenses (1.30E-10 Gy/Bq) organs, respectively. Furthermore, the 225Ac absorbed dose in the prostate organ was obtained 1.91E-9 Gy/Bq, where this value is 1% of total body dose. While the absorbed dose distribution of 225Ac in body organs shows the highest concentration in the spleen (1.47E-8 Gy/Bq) and lowest in the eye lenses (7.93E-12 Gy/Bq). CONCLUSION: The absorbed dose in the body organs due to 223Ra and 225Ac α-emitter radiopharmaceuticals which are used in metastasized castration-resistant prostate cancer (mCRPC), calculated in this study. The results of this study will assist in evaluating and analyzing human body organ doses from application of 223Ra and 225Ac that used in mCRPC patients.

Sequencing radium 223 and other life-prolonging agents in castration-resistant prostate cancer patients.

Background: Radium 223 (RA223) is currently administered as part of a therapeutic sequence with the other life-prolonging agents (LPAs) for metastatic castration-resistant prostate cancer (mCRPC). Patients & methods: We retrospectively reviewed the clinical records of patients who had received at least three LPAs including RA223. Results: Median overall survival (OS) from the start of first-line treatment was 39.8 months, with the patients who completed all six planned courses of RA223 having a longer OS than those who did not (53.2 vs 29.5 months; p < 0.0001). Conclusions: Our study confirms the activity of RA223 regardless of the treatment line in which it is administered and suggests that patient selection plays a central role in maximizing this activity.

Manejo de pacientes con CPRCm tratados con dicloruro de radio-223 en el escenario del brote de COVID-19 / Management of mCRPC patients treated with 223Radium-dicloride in the scenario of the COVID-19 outbreak

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Assessing the quality of life of patients with metastatic castration-resistant prostate cancer with bone metastases receiving [223Ra]RaCl2 therapy.

[Ra]RaCl2 dichloride treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) is associated with improved overall survival (OS) and a delay in the time to the first symptomatic skeletal-related event. The aim of this study was to evaluate the quality of life (QoL) of patients with mCRPC receiving [Ra]RaCl2 treatment using the European Organization for Research and Treatment of Cancer (EORTC) validated questionnaire form.Thirty patients with mCRPC were included in this study. The patients were administered the EORTC QLQ-C30 (version 3.0) questionnaire at 5 time points: before [Ra]RaCl2 treatment, after the first cycle, after the third cycle, after the fifth cycle, and at the end of the treatment.Median age at diagnosis was 65.2 years (range, 49.1-75.5). There was a significant 25% drop in the median alkaline phosphatase levels: 101 U/L (range, 58-594) vs. 75 U/L (39-649) before and during treatment, respectively (P = .003). The median dose of [Ra]RaCl2 for all patients was 4.1 MBq (range, 3.35-6.55), and the majority of patients received 5 treatment cycles (range 3-6). Seventeen patients were alive at the end of treatment (56.7%). The median OS was 26 months (range, 19.8-32.2). All of the patients filled out the questionnaires at the first 3 time points; the fourth survey included 28 patients, and only 23 patients completed the fifth questionnaire. Compared to the baseline, only the scale "role functioning" showed a temporary worsening after the first therapy cycle (P = .03). In subsequent cycles, its mean value rose to initial levels. All other functional and symptom scales, as well as global health status, remained constant over all 5 time points and showed no significant changes (P > .05).[Ra]RaCl2 therapy does not adversely impair the health-related QoL of patients with mCRPC and bone metastasis. Only patients' role functioning worsened temporarily after the first therapy cycle but stabilized in subsequent treatment cycles.

The potential of PSMA-targeted alpha therapy in the management of prostate cancer.

INTRODUCTION: Alpha emitters present several advantages for cancer therapy. The radiopharmaceutical 223Ra-dichloride has been recently introduced for the targeted alpha therapy (TAT) of metastastic castration-resistant prostate cancer (mCRPC). However, since 223Ra-dichloride targets only skeletal lesions, its use in clinical practice is recommended only in subjects without visceral metastases. To overcome this, several efforts have been made to develop radiopharmaceuticals suitable for TAT and specifically directed toward the biomarker prostate specific membrane antigen (PSMA), overexpressed by both skeletal and visceral metastases from mCRPC. AREAS COVERED: The radiobiological principles concerning TAT applications are covered, with particular emphasis on its pros and cons, especially in comparison with beta-emitter radionuclide therapy. Furthermore, the role of PSMA as a theranostic target for imaging and therapy is reviewed. Lastly, the pre-clinical and clinical applications of TAT through 225Actinium (225AC) and 213Bismuth (213Bi) are discussed. EXPERT OPINION: PSMA-based TAT holds the promise of becoming a powerful tool for the management of mCRPC. Nevertheless, several issues have still to be addressed, especially concerning TAT toxicity. Furthermore, several efforts have to be made for identifying the more adequate alpha-emitter (225Ac vs 213Bi) with a view to the patient's tailored therapeutic approach.

An agent-based model of prostate Cancer bone metastasis progression and response to Radium223.

BACKGROUND: Bone metastasis is the most frequent complication in prostate cancer patients and associated outcome remains fatal. Radium223 (Rad223), a bone targeting radioisotope improves overall survival in patients (3.6 months vs. placebo). However, clinical response is often followed by relapse and disease progression, and associated mechanisms of efficacy and resistance are poorly understood. Research efforts to overcome this gap require a substantial investment of time and resources. Computational models, integrated with experimental data, can overcome this limitation and drive research in a more effective fashion. METHODS: Accordingly, we developed a predictive agent-based model of prostate cancer bone metastasis progression and response to Rad223 as an agile platform to maximize its efficacy. The driving coefficients were calibrated on ad hoc experimental observations retrieved from intravital microscopy and the outcome further validated, in vivo. RESULTS: In this work we offered a detailed description of our data-integrated computational infrastructure, tested its accuracy and robustness, quantified the uncertainty of its driving coefficients, and showed the role of tumor size and distance from bone on Rad223 efficacy. In silico tumor growth, which is strongly driven by its mitotic character as identified by sensitivity analysis, matched in vivo trend with 98.3% confidence. Tumor size determined efficacy of Rad223, with larger lesions insensitive to therapy, while medium- and micro-sized tumors displayed up to 5.02 and 152.28-fold size decrease compared to control-treated tumors, respectively. Eradication events occurred in 65 ± 2% of cases in micro-tumors only. In addition, Rad223 lost any therapeutic effect, also on micro-tumors, for distances bigger than 400 µm from the bone interface. CONCLUSIONS: This model has the potential to be further developed to test additional bone targeting agents such as other radiopharmaceuticals or bisphosphonates.

Decreasing undesirable absorbed radiation to the intestine after administration of radium-223 dichloride for treatment of bone metastases.

[223Ra]RaCl2 is the first alpha-particle emitting radiopharmaceutical to be used for castration-resistant prostate cancer patients with bone metastases because of its excellent therapeutic effects. [223Ra]RaCl2 is excreted via the intestine into feces, and some is absorbed from the intestine into the blood, which may be undesirable in terms of the exposure to radiation. Recently, we showed that a complex of myo-inositol-hexakisphosphate (InsP6) with zinc is a useful decorporation agent against radiostrontium. In this study, we hypothesized that Zn-InsP6 could bind to not only strontium but also to radium, and could inhibit the absorption of radium from the intestine. In in vitro binding experiments, Zn-InsP6 showed a high binding affinity for radium. In in vivo biodistribution experiments by intravenous injection of [223Ra]RaCl2 after treatment of Zn-InsP6, mice treated with Zn-InsP6 showed significantly lower bone accumulation of radioactivity (34.82 ± 1.83%Dose/g) than the mice in the non-treatment control group (40.30 ± 2.78%Dose/g) at 48 h postinjection. These results indicate that Zn-InsP6 bound radium in the intestine and inhibited the absorption of radium into the blood. Therefore, the insoluble Zn-InsP6 complex has high potential to decrease the side effects of [223Ra]RaCl2.

Feasibility of Thorium-227/Radium-223 Gamma-Camera Imaging During Radionuclide Therapy.

Thorium-227 (227Th) is a long-lived (T1/2 = 18.7 d) α-emitter that has emerged as candidate for radioimmunotherapy. Imaging of patients treated with thorium-227 conjugates is challenging due to the low activity administered and to photon emissions with low yields. In addition, the radioactive daughter radium-223 (223Ra) have photon emissions in the same energy range as 227Th. The long half-life of 223Ra (T1/2 = 11.4 d) and the possibility of redistribution motivates efforts to separate 227Th and 223Ra. The aim of this study was to investigate the feasibility of imaging of patients treated with 227Th-labeled-monoclonal antibody (mAb) and to determine acquisition and image processing parameters to enable discrimination between 227Th and 223Ra. Imaging was performed with a GE Discovery 670 NM/CT γ-camera. Radionuclide separation with different energy windows (EW) and collimators was studied in images of vials with either 227Th or 223Ra. Phantom acquisitions with clinically relevant activities were performed to assess image quality and the usefulness of background subtraction and spatial filtering. Two patients treated with 227Th-labeled-mAb were imaged. Imaging of vials showed that 223Ra can be distinguished from 227Th using multiple energy windows. Medium- and high-energy collimators showed similar performance of sensitivity and spatial resolution, whereas the low-energy collimator had higher sensitivity but poor resolution due to collimator penetration. Visually, the image quality was improved with background subtraction and spatial filtering. The patient images exhibited the expected image quality and a possibility to separate 227Th and 223Ra. γ-Camera imaging of patients treated with 227Th-mAb is feasible and 223Ra can be distinguished from 227Th. Image quality is substantially improved using background subtraction and a spatial smoothing filter. Acquisition settings recommended for planar images are: high-energy general purpose or medium-energy general purpose collimator, 40 min acquisition time and energy windows: (1) 70-100 keV (227Th and 223Ra); (2) 215-260 keV (227Th); (3) 260-290 keV (223Ra); (4) 350-420 keV (223Ra).

A phase II randomized trial of RAdium-223 dichloride and SABR Versus SABR for oligomEtastatic prostate caNcerS (RAVENS).

BACKGROUND: Metastasis directed therapy (MDT) for patients with oligometastatic disease is associated with improvements in progression free survival (PFS) and overall survival (OS) compared to systemic therapy alone. Additionally, within a prostate-cancer-specific cohort, MDT is able to forestall initiation of androgen deprivation therapy (ADT) in men with hormone-sensitive, oligometastatic prostate cancer (HSOPCa) compared to observation. While MDT appears to be safe and effective in HSOPCa, a large percentage of men will eventually have disease recurrence. Patterns of failure in HSOPCa demonstrate patients tend to have recurrence in the bone following MDT, raising the question of sub-clinically-apparent osseous disease. Radium-223 dichloride is a radiopharmaceutical with structural similarity to calcium, allowing it to be taken up by bone where it emits alpha particles, and therefore might have utility in the treatment of micrometastatic osseous disease. Therefore, the primary goal of the phase II RAVENS trial is to evaluate the efficacy of MDT + radium-223 dichloride in prolonging progression free survival in men with HSOPCa. METHODS: Patients with HSOPCa and 3 or less metastases with at least 1 bone metastasis will be randomized 1:1 to stereotactic ablative radiation (SABR, also known as stereotactic body radiation therapy (SBRT)) alone vs SABR + radium-223 dichloride with a minimization algorithm to balance assignment by institution, primary intervention, prior hormonal therapy, and PSA doubling time. SABR is delivered in one to five fractions and patients in the SABR + radium-223 dichloride arm will receive six infusions of radium-223 dichloride at four-week intervals. The primary end point is progression free survival. The secondary clinical endpoints include toxicity and quality of life assessments, local control at 12 months, locoregional progression, time to distant progression, time to new metastasis, and duration of response. DISCUSSION: The RAVENS trial will be the first described phase II, non-blinded, randomized study to compare SABR +/- radium-223 dichloride in patients with HSOPCa and 3 or less metastases with at least one bone metastasis. The primary hypothesis is that SABR + radium-223 dichloride will increase median progression-free survival from 10 months in the SABR arm to 20 months in the SABR + radium-223 dichloride arm. TRIAL REGISTRATIONS: Clinicaltrials.gov. Identifier: NCT04037358. Date of Registration: July 30, 2019. Date of First Participant Enrolled: August 9, 2019. Date of Last Approved Amendment: October 16, 2019. Protocol Version: Version 5.

Pharmacotherapeutic strategies for castrate-resistant prostate cancer.

INTRODUCTION: Metastatic castration-resistant prostate cancer (CRPC) is a potentially symptomatic disease with an eventual lethal outcome. Novel pharmaceutical agents are continuously studied with encouraging results in CRPC. AREAS COVERED: In this perspective, the authors present established and promising pharmacotherapeutic strategies for the management of CRPC; both with and without metastases. Apart from the different treatment strategies, the authors present the relevant sequence of treatment through disease progression. EXPERT OPINION: Usually, docetaxel should be considered the first line treatment in mCRPC. Abiraterone acetate (AA) plus prednisone or enzalutamide (ENZ) could be alternative treatments in chemotherapy naïve patients. Sipuleucel-T has been approved for the treatment of asymptomatic or minimally symptomatic mCRPC. Ra-223 has been approved for patients with mCRPC with symptomatic bone metastases (not visceral metastases). Cabazitaxel has been approved as the second line treatment to docetaxel in mCRPC. No differences in the overall survival has been observed between sequences starting with docetaxel versus AA/ENZ. Between AA-to-ENZ and ENZ-to-AA sequence, the AA-to-ENZ sequence appeared to be more favorable than the ENZ-to-AA regarding progression-free survival but not overall survival. Carbazitaxel seemed to retain its activity regardless of the treatment sequence. Of note, ENZ and apalutamide have been approved in non-metastatic CRPC.

Real-world outcomes of radium-223 dichloride for metastatic castration resistant prostate cancer.

Aim: Timing of radium-223 (Ra-223) in metastatic castration-resistant prostate cancer (mCRPC) remains challenging due to alternative options and short window of opportunity. Methods: Ra-223 treated patients in the CAPRI-registry were included. Outcomes were evaluated based on treatment line of Ra-223. Results: Out of 285 patients, 49% received Ra-223 in line ≥3. 51% completed six Ra-223 injections and 34% had a symptomatic skeletal event after first Ra-223 without differences between subgroups. After correction of known prognostic factors Ra-223 in line ≥3 (HR: 3.267; 95% CI: 1.689-6.317; p < 0.01) remained associated with worse OS. Conclusion: In the Netherlands, Ra-223 was mainly started as second or third mCRPC-treatment in 2014-2018. Later timing of Ra-223 did affect OS, but not treatment completion and occurrence of symptomatic skeletal events.

Administration of lower doses of radium-224 to ankylosing spondylitis patients results in no evidence of significant overall detriment.

The use of low doses of radium-224 (224Ra) chloride for the treatment of ankylosing spondylitis was stopped following the discovery that patients treated with it had a higher than control incidence of leukaemia and other cancers. This was so even though the treatment resulted in decreased pain and increased mobility-both of which are associated with decreased mortality. It was decided to re-analyze the epidemiological data looking at all causes of death. The risk of leukaemia, solid cancer, death from non-cancer causes and from all causes in a study populations of men that received either the typical dose of 5.6 to 11.1 MBq of 224Ra, any dose of 224Ra or no radium were compared using the Cox proportional hazard model. For patients that received the typical dose of 224Ra agreed with the excess cancer was similar to that reported in previous studies. In contrast, these patients were less likely to die from non-cancer diseases and from all causes of death than the control patients. No excess mortality was also found in the population of all males that received the radionuclide. It is concluded that 224Ra treatment administered at low doses to patients with ankylosing spondylitis did not impact mortality from all causes. The study demonstrates the need to consider all causes of death and longevity when assessing health impacts following irradiation.

Preclinical Single Photon Emission Computed Tomography of Alpha Particle-Emitting Radium-223.

Objective: Dose optimization and pharmacokinetic evaluation of α-particle emitting radium-223 dichloride (223RaCl2) by planar γ-camera or single photon emission computed tomography (SPECT) imaging are hampered by the low photon abundance and injected activities. In this study, we demonstrate SPECT of 223Ra using phantoms and small animal in vivo models. Methods: Line phantoms and mice bearing 223Ra were imaged using a dedicated small animal SPECT by detecting the low-energy photon emissions from 223Ra. Localization of the therapeutic agent was verified by whole-body and whole-limb autoradiography and its radiobiological effect confirmed by immunofluorescence. Results: A state-of-the-art commercial small animal SPECT system equipped with a highly sensitive collimator enables collection of sufficient counts for three-dimensional reconstruction at reasonable administered activities and acquisition times. Line sources of 223Ra in both air and in a water scattering phantom gave a line spread function with a full-width-at-half-maximum of 1.45 mm. Early and late-phase imaging of the pharmacokinetics of the radiopharmaceutical were captured. Uptake at sites of active bone remodeling was correlated with DNA damage from the α particle emissions. Conclusions: This work demonstrates the capability to noninvasively define the distribution of 223RaCl2, a recently approved α-particle-emitting radionuclide. This approach allows quantitative assessment of 223Ra distribution and may assist radiation-dose optimization strategies to improve therapeutic response and ultimately to enable personalized treatment planning.

Primary Radical Prostatectomy or Ablative Radiotherapy as Protective Factors for Patients With mCRPC Treated With Radium-223 Dichloride: An Italian Multicenter Study.

BACKGROUND: We investigated, in a real-life setting, the prognostic relevance of previous primary treatment (radical prostatectomy [RP] or external beam radiotherapy [EBRT]) on overall survival for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (223Ra). MATERIALS AND METHODS: In the present multicenter retrospective study, we enrolled 275 consecutive patients. The demographic and clinical data and mCRPC characteristics were recorded and evaluated at baseline and at the end of treatment or progression. 223Ra was administered according to the current label authorization until disease progression or unacceptable toxicity. We divided the whole cohort into 2 groups: those who had undergone primary radical prostatectomy or ablative radiotherapy (RP/EBRT) and those who had not received previous primary treatment (NO). RESULTS: Of the 275 patients, 128 (46.5%) were alive and undergoing monitoring at the last follow-up examination, 103 (37.4%) had stopped treatment because of disease progression or the onset of comorbidities, and 147 (53.5%) had died during the study period. Of the 275 patients, 132 were in the RP/EBRT group (48%), of whom 93 had undergone RP and 76 had undergone ablative EBRT, and 143 patients were in the NO group (52%). The data showed a clear advantage for the patients in the RP/EBRT group compared with those in the NO group, with an estimated median survival of 18 versus 11 months, respectively (P < .001). The results from the multivariate analysis corroborated this trend, with a hazard ratio of 0.7 (P = .0443), confirming the better outcome for the RP/EBRT group. CONCLUSIONS: Previous radical treatment provides a protective role for patients with mCRPC undergoing 223Ra treatment.

Targeted α-Therapy in Cancer Management: Synopsis of Preclinical and Clinical Studies.

The approval of 223Ra dichloride (223RaCl2) in 2013 was a principal event in introducing targeted α-therapy as a form of safe and effective management strategy in cancer. There is an increasing interest in research and development of new targeted α-therapy agents spearheaded by advancements in cancer biology, radiochemistry, and availability of clinically relevant α particles. There are active clinical studies on sequencing or combining 223RaCl2 with other drug regimens in the setting of metastatic prostate cancer and in other cancers such as osteosarcoma and bone-dominant breast cancer. Targeted α-therapy strategy is also being actively explored through many preclinical and few early clinical studies using 225Ac, 213Bi, 211At, 227Th, and 212Pb. Investigations incorporating 225Ac are more robust and active at this time with promising results. The author provide a brief synopsis of the preclinical and clinical studies in the rapidly evolving field of targeted α-therapy in cancer management.

The Relationship Between Total Lesion Activity on 18F Choline Positron Emission Tomography-Computed Tomography and Clinical Outcome in Patients with Castration-Resistant Prostate Cancer Bone Metastases Treated with 223Radium.

The aim of the study was to assess the correlation between metabolic response measured through positron emission tomography-computed tomography (PET-CT) with 18F choline (18F FCH) and overall survival (OS) in patients affected by bone lesions from metastatic castration-resistant prostate cancer treated with 223Ra dichloride. Eleven subjects were subjected to PET-CT with 18F FCH before and 1 month after 223Ra treatment. Reduction in total lesion activity (ΔTLA) between pretreatment and post-treatment scan was determined and patients were divided into responders (ΔTLA >50%) and nonresponders (ΔTLA <50%). The OS of the entire cohort was 12.7 ± 3.8 months. Kaplan-Meier analysis showed that responders presented a significantly longer survival than nonresponders (16.5 ± 1.9 months vs. 10.5 ± 0.9 months, p < 0.05). Reduction in TLA after 223Ra treatment seems to be correlated with a trend toward a longer survival.