HIFU Therapy Research Articles

An Ultrasound Image-Based Dynamic Fusion Modeling Method for Predicting the Quantitative Impact of In Vivo Liver Motion on Intraoperative HIFU Therapies: Investigations in a Porcine Model.

Organ motion is a key component in the treatment of abdominal tumors by High Intensity Focused Ultrasound (HIFU), since it may influence the safety, efficacy and treatment time. Here we report the development in a porcine model of an Ultrasound (US) image-based dynamic fusion modeling method for predicting the effect of in vivo motion on intraoperative HIFU treatments performed in the liver in conjunction with surgery. A speckle tracking method was used on US images to quantify in vivo liver motions occurring intraoperatively during breathing and apnea. A fusion modeling of HIFU treatments was implemented by merging dynamic in vivo motion data in a numerical modeling of HIFU treatments. Two HIFU strategies were studied: a spherical focusing delivering 49 juxtapositions of 5-second HIFU exposures and a toroidal focusing using 1 single 40-second HIFU exposure. Liver motions during breathing were spatially homogenous and could be approximated to a rigid motion mainly encountered in the cranial-caudal direction (f = 0.20Hz, magnitude >13mm). Elastic liver motions due to cardiovascular activity, although negligible, were detectable near millimeter-wide sus-hepatic veins (f = 0.96Hz, magnitude <1mm). The fusion modeling quantified the deleterious effects of respiratory motions on the size and homogeneity of a standard “cigar-shaped” millimetric lesion usually predicted after a 5-second single spherical HIFU exposure in stationary tissues (Dice Similarity Coefficient: DSC<45%). This method assessed the ability to enlarge HIFU ablations during respiration, either by juxtaposing “cigar-shaped” lesions with spherical HIFU exposures, or by generating one large single lesion with toroidal HIFU exposures (DSC>75%). Fusion modeling predictions were preliminarily validated in vivo and showed the potential of using a long-duration toroidal HIFU exposure to accelerate the ablation process during breathing (from 0.5 to 6 cm3·min-1). To improve HIFU treatment control, dynamic fusion modeling may be interesting for assessing numerically focusing strategies and motion compensation techniques in more realistic conditions.

The feasibility of using arterial spin labeling for visualization of non perfused volumes after HIFU treatment in the kidney

MR guidance of High Intensity Focused Ultrasound (MFgHIFU) ablation offers the possibility to determine if complete tumor ablation has been established based on imaging the non-perfused volume (NPV). For thermal therapy, contrast enhanced (CE) imaging with a gadolinium-based contrast agent is currently the golden standard to quantify the NPV. A drawback of this method is that gadolinium based intra-vascular contrast agents interfere with HIFU therapy in two ways. First, ablation can release toxic free gadolinium, by long-term decomposition of the encapsulating chelate. Second, it degrades the quality of MR-thermometry. Therefore, even if residual viable tumor tissue is observed with CE-MRI, the treatment cannot be continued. To address this problem for HIFU interventions on the kidney, this study explores other means of perfusion imaging, such as Arterial Spin Labeling (ASL). Petros Martirosan’s group at the University of Tubingen used Flow-sensitive Alternating Inversion Recovery (FAIR) to image perfusion in the kidneys without the use of contrast agents. This in vivo study on a porcine model investigates if ASL potentially allows to perform NPV measurements during therapy and to continue the intervention if incomplete ablation of the target volume is observed.

The relationship of area under temperature curve during MR guided HIFU and diffusion coefficient in patient screening

Different type of fibroid shows different response to MR guided HIFU, which is believed to reflect different blood suplly. ADC value derived from low b multiple b value DWI may reflect perfusion information. Our study is to assess the relationship of AUC (area under curve) calculated from the temperature curve during sonication in MR guided HIFU therapy for fibroid and the diffusion coefficient derived from multiple b-values DW-MRI in patient screening.

Does focal high-intensity focused ultrasound have a role in treating localized prostate cancer in the elderly?

133 Background: There is an increase in the ageing population leading a significant proportion of men diagnosed with prostate cancer being over 75 years of age. Misconceptions regarding treating the elderly are still rife. The body of evidence that has recently emerged shows that this cohort of patients should be offered the same curative therapies as their counterparts. This study looks at the feasibility of focal HIFU in treating localised prostate cancer in those aged over 75 years of age. Methods: Our independent academic HIFU registry incorporates a total of 60 patients who were diagnosed with low, intermediate and high risk localized adenocarcinoma of the prostate, stage T2a-T3aN0M0 and treated with focal HIFU using Sonablate500, between 2004 and 2014. We divided the patient cohort into those that were treated within the remit of a trial protocol, and those that were not. Results: As biochemical failure is difficult to define, we looked at the medium-term transition rates to redo HIFU, local salvage and systemic therapy. 12% required re-treatment with HIFU. 8% transitioned into local salvage or systemic therapy of which 1 patient had radiotherapy and 4 were subsequently treated with androgen deprivation therapy). The table below outlines the complication rates associated with focal HIFU. Conclusions: Focal HIFU has been shown to be both feasible and effective in the elderly population. It is a safe modality of treatment to use in this patient cohort with a low complication profile. Long-term studies are however necessary. [Table: see text]

VE17: Robot-assisted laparoscopic YV-plasty in patients with refractory bladder neck contracture

We present preliminary results of a case series on refractory bladder neck contracture (BNC) treated with robot-assisted laparoscopic Y-V plasty (RAYV). Between 01/2013 and 02/2016, 12 consecutive adult male patients underwent RAYV in our hospital. BNC developed after transurethral procedures (n = 9), simple prostatectomy (n = 2) and HIFU therapy of the prostate (n = 1). Each patient had had multiple unsuccessful previous endoscopic treatments. All RAYV procedures were performed using a transperitoneal six-port approach (four-arm robotic setting). There were no intraoperative or major postoperative complications. During a median follow-up of 23.2 months two cases of refractory BNC were observed. In both cases a postoperative International Prostate Symptom Score (IPSS) of 20 and 25 was reported, respectively. In contrast, amongst the patients without evidence of refractory BNC the median IPSS was 6.5 reflecting an only mildly impaired voiding function in most cases, thus, suggesting a treatment success in 83.3% of patients. To the best of our knowledge, this is the first report on RAYV for refractory BNC. In our series RAYV was feasible in all patients, and only two cases of refractory BNC were reported during a median follow-up of almost 2 years. At the same time, no intraoperative or major postoperative complications were observed. More clinical data with a longer follow-up are needed in this promising field to reveal the actual efficacy and relevance of RAYV.

Dynamic contrast-enhanced ultrasonographic (DCE-US) assessment of the early response after combined gemcitabine and HIFU with low-power treatment for the mouse xenograft model of human pancreatic cancer.

To assess therapeutic efficacy of gemcitabine and HIFU for a mouse model of pancreatic cancer, and the role of DCE-US for predicting early treatment response compared with pathology. In 48 PANC-1- nude mice (G1, HIFU_higher power [n = 14]; G2, gemcitabine [n = 12]; G3, combined gemcitabine and HIFU_low power [n = 12]; and G4, control [n = 10]), pulsed HIFU or gemcitabine therapy was used. DCE-US was performed 1 day before and after first treatment. Seven DCE-US perfusion parameters were obtained. Therapeutic efficacy was estimated using necrotic fraction and apoptosis. Correlation between tumour size and US perfusion parameters was analysed. Pathology results showed that combined gemcitabine and HIFU using low-power treatment had a more effective response than other treatments, including in the control group, i.e. necrotic fraction: 40.5 ± 4.9 vs. 16.9 ± 8.0, p = 0.000 and apoptosis: 44.3 ± 29.4 vs. 7.9 ± 4.9, p = 0.002. In this group, US perfusion parameters, including peak intensity (22.6 ± 22.6 vs. 9.6 ± 6.3, p = 0.002), AUC (961.8 ± 96.9 vs. 884.4 ± 91.4, p = 0.000), and AUCout (799.9 ± 75.6 vs. 747.1 ± 77.9, p = 0.000), had significantly decreased 1 day following first treatment (p < 0.05). In addition, peak intensity, AUC, and AUCout showed a tendency to decrease in treated groups. Alternatively, peak intensity, AUC, and AUCout showed a tendency to increase in control group. Gemcitabine and HIFU were more effective and safer than other treatments. US perfusion parameters were useful for predicting early therapeutic response 1 day following treatment. Recently, treatment of pancreatic cancer has changed based on a multidisciplinary approach. Combined gemcitabine_HIFU demonstrated more effective therapeutic response than other treatments. DCE-US is useful for predicting early therapeutic response 1 day after treatment. In the combined group, PI, AUC, and AUC (out) decreased 1 day after treatment.

Hollow iron-silica nanoshells for enhanced high intensity focused ultrasound

BackgroundHigh intensity-focused ultrasound (HIFU) is an alterative ablative technique currently being investigated for local treatment of breast cancer and fibroadenomas. Current HIFU therapies require concurrent magnetic resonance imaging monitoring. Biodegradable 500 nm perfluoropentane-filled iron-silica nanoshells have been synthesized as a sensitizing agent for HIFU therapies, which aid both mechanical and thermal ablation of tissues. In low duty cycle high-intensity applications, rapid tissue damage occurs from mechanical rather than thermal effects, which can be monitored closely by ultrasound obviating the need for concurrent magnetic resonance imaging. Materials and methodsIron-silica nanoshells were synthesized by a sol-gel method on polystyrene templates and calcined to yield hollow nanoshells. The nanoshells were filled with perfluoropentane and injected directly into excised human breast tumor, and intravenously (IV) into healthy rabbits and Py8119 tumor-bearing athymic nude mice. HIFU was applied at 1.1 MHz and 3.5 MPa at a 2% duty cycle to achieve mechanical ablation. ResultsEx vivo in excised rabbit livers, the time to visually observable damage with HIFU was 20 s without nanoshells and only 2 s with nanoshells administered IV before sacrifice. Nanoshells administered IV into nude mice with xenograft tumors were activated in vivo by HIFU 24 h after administration. In this xenograft model, applied HIFU resulted in a 13.6 ± 6.1 mm3 bubble cloud with the IV injected particles and no bubble cloud without particles. ConclusionsIron-silica nanoshells can reduce the power and time to perform HIFU ablative therapy and can be monitored by ultrasound during low duty cycle operation.

A continuous tri-phase transition effect for HIFU-mediated intravenous drug delivery

Aiming at substantially enhanced efficacy and biosafety of clinical HIFU therapy, a natural solid medium, L-menthol (LM), characteristic of mild and controllable “solid-liquid-gas” (SLG) tri-phase transition, was adopted, instead of those conventional explosive liquid–gas (LG) bi-phase transitional media, in constructing a multifunctional theranostic system. Owing to the continuous and controllable characteristics of SLG tri-phase transition, such a novel tri-phase transition-based theranostic system has been demonstrated of the repeatedly enhanced HIFU efficacy ex vivo and in vivo under once intravenous injection and the significantly improved treatment precision, controllability and biosafety when comparing to the traditional bi-phase transition medium, perfluorohexane (PFH), thus promising great application potential in clinical HIFU treatment. Moreover, this theranostic system has been demonstrated a long blood-circulation lifetime and continuous accumulation in tumor in 24 h, which is very beneficial for the enhanced tumor ablation in vivo along with SLG tri-phase transition. More importantly, after loading multiple model drugs and real drug, such a theranostic system presents a HIFU-mediated temperature-responsive drug release property, and depending on the versatile miscibility of LM, co-loadings with hydrophobic and hydrophilic drugs are also achieved, which provides the possibility of synergistic treatment combining HIFU therapy and chemotherapy.

MP62-03 HIGH-INTENSITY FOCUSSED ULTRASOUND IN THE TREATMENT OF LOCALISED PROSTATE CANCER: FOCAL SALVAGE TRANSITION RATES

INTRODUCTION AND OBJECTIVES: Focal therapy has shown encouraging low rates of genitourinary side-effects in the treatment of localised prostate cancer. As biochemical failure is difficult to define discussion has centred on rates of transition to whole-gland local therapy and need for systemic therapy. We report on our registry experience of over 1,000 men treated with transrectal HIFU. METHODS: Our independent academic HIFU registry incorporates a total of 830 patients with low, intermediate and high risk, stage T2a-T3aN0M0 prostate adenocarcinoma treated between 2004 and 2012 in a primary setting. Of these, 509 had focal HIFU treatment (Sonablate 500); 313 had whole-gland treatment. We defined our composite failure as need for whole-gland therapy and/or systemic therapy. RESULTS: Of 509 men undergoing focal HIFU therapy, 84 required redo-HIFU (17%). None of the patients in this group went on to have radical prostatectomy. 1% (5/509) had salvage radiotherapy and <0.5% (1/509) had salvage chemotherapy due to lung metastases following a renal primary. 1% (5/509) were subsequently treated with androgen deprivation therapy alone. In the same period, 313 patients had whole-gland HIFU treatment. Of these, 40% (124/313) had redo-HIFU and 5% (15/313) had androgen deprivation for treatment failure. 6% (18/313) underwent salvage radiotherapy and <1% (2/313) were further treated with salvage radical prostatectomy. <0.5% (1/313) had salvage chemotherapy and <0.5% (1/313) had cryotherapy. CONCLUSIONS: Focal therapy demonstrates reassuringly low short to medium term rates of transition to whole-gland local therapy or systemic therapy in 11%. Longer follow-up will determine rates of metastases and mortality.

Planning of HIFU therapies of moving organs by using numerical simulation techniques

Background We present a software prototype that allows for preinterventional planning and simulation of focused ultrasound therapies. By using numerical simulation techniques the heating and destruction of the tissue can be predicted and thus a patient-specific treatment plan can be generated in advance. Since our simulation is amenable to respect rib shielding, organ motion as well as focal point tracing, it could in particular support the planning of liver treatments. Material and methods The simulation of the ultrasound propagation is based on the hybrid angular spectrum method. The heating of the tissue is computed by solving the Pennes bioheat equation. Both simulations have been massively parallelized on graphics processing units to improve computation times. The simulation of the pressure field includes single reflection of the ultrasound beams at acoustically dense structures as the ribs. Technically, these reflections are computed by a so-called back-sweep of the spectral propagator. Moreover, motion of the tissue is incorporated in the simulation by allowing the material parameters to be updated in each simulation step. Additionally, heat transportation of moving tissue is respected in the bioheat equation solver. By adjusting the transducer parameters for electronic steering, we can simulate focal point tracing in moving organs. Based on the temperature field, we also predict the thermal damage by computing the Arrhenius damage model. Results Our approach allows for the simulation of entire treatment plans composed of a set of sonications and cooling phases. For a 40s sonication simulated at a resolution of 256x256x256 pressure samples and 128x128x128 temperature samples we observe computation times of 19s if we recompute the ultrasound field 15 times per breathing cycle. Therefore, due the parallelization approach the treatment can be simulated faster than real time in moving organs. Conclusion Due to the exploitation of graphics processing units, we are able to simulate HIFU treatments in moving organs faster than real time. By simulating the pressure as well as the temperature field and the thermal damage we can predict the treatment results depending on changes of the hardware parameters such as phase shifts or power per element. Based on this simulation, a detailed pre-interventional treatment planning for liver tumors becomes possible.

Factors affecting tumor ablation during high intensity focused ultrasound treatment.

Background/AimsHigh intensity focused ultrasound (HIFU) utilizes a targeted extracorporeal focused ultrasound beam to ablate neoplastic pancreatic tissue. We used an in vitro model to examine the effects of bone, metallic stents, plastic stents, metal plates, and cyst-like lesions on HIFU treatment.MethodsHIFU was delivered to the phantom models implanted with foreign bodies, and the location, shape, and size of the ablated zones were evaluated.ResultsBone and metallic plates reflected the ultrasound beam, shifting the ablation zone from the focal zone to the prefocal area. In the phantoms containing metal stent, plastic stent, and cyst, most of the ablative energy was reflected to the prefocal area by the surface, with the remainder penetrating through the phantom. The area of the ablated margins was significantly larger in size and volume than the intended focal ablation zone.ConclusionsDuring HIFU therapy, artificial or anatomical barriers could affect the direction of the ultrasound beams, shifting the ablation zone from the focal area to a prefocal site with a larger than expected ablation zone. These factors should be considered prior to HIFU treatment for pancreatic tumors because they could limit ablation success, in addition to causing complications.

New clinical application of high-intensity focused ultrasound: local control of synovial sarcoma

High-intensity focused ultrasound (HIFU) is playing an increasingly important role in cancer therapy. Primary synovial sarcomas of the chest wall are extremely rare. We report the first case of noninvasive HIFU therapy for the control of synovial sarcoma. A 51-year-old man was diagnosed with spindle cell sarcoma on the left chest wall through lumpectomy. After four cycles of chemotherapy, local recurrence of the sarcoma was detected. Subsequent extended resection confirmed synovial sarcoma. After five cycles of a new chemotherapy option, the sarcoma relapsed again. Then the patient received five courses of HIFU; this completely ablated the sarcoma without complications. No chemotherapy, radiotherapy, or biological therapy has been applied since. Now the patient is stable and has a high quality of life.

Whole-gland Ablation of Localized Prostate Cancer with High-intensity Focused Ultrasound: Oncologic Outcomes and Morbidity in 1002 Patients

BackgroundHigh-intensity focused ultrasound (HIFU) is a nonsurgical therapy for selected patients with localized prostate cancer (PCa). ObjectiveThe long-term oncologic and morbidity outcomes of primary HIFU therapy for localized PCa were evaluated in a prospective, single-arm, single-institution cohort study. Design, setting, and participantsParticipants were patients treated with HIFU for localized PCa from 1997 to 2009. Excluded were patients with local recurrence following radiotherapy. A second HIFU session was systematically performed in patients with biopsy-proven local recurrence. InterventionWhole-gland prostate ablation with transrectal HIFU. Outcome measurements and statistical analysisIncontinence was assessed using the Ingelman-Sundberg score, and potency was assessed using the five-item version of the International Index of Erectile Function (IIEF-5) scores. Primary outcomes were survival rates (biochemical-free, cancer-specific, metastasis-free, and overall survival). Secondary outcomes were morbidity rates. Median follow-up was 6.4 yr (range: 0.2–13.9). The Kaplan-Meier method was used to determine survival estimates, and multivariate analysis was used to determine predictive factors of biochemical progression. Results and limitationsA total of 1002 patients were included. The median nadir prostate-specific antigen (PSA) was 0.14 ng/ml, with 63% of patients reaching a nadir PSA ≤0.3 ng/ml. Sixty percent of patients received one HIFU session, 38% received two sessions, and 2% received three sessions. The 8-yr biochemical-free survival rates (Phoenix definition) were 76%, 63%, and 57% for low-, intermediate-, and high-risk patients, respectively (p < 0.001). At 10 yr, the PCa-specific survival rate and metastasis-free survival rate (MFSR) were 97% and 94%, respectively. Salvage therapies included external-beam radiation therapy (EBRT) (13.8%), EBRT plus androgen-deprivation therapy (ADT) (9.7%), and ADT alone (12.1%). Severe incontinence and bladder outlet obstruction decreased with refinement in the technology, from 6.4% and 34.9% to 3.1% and 5.9%, respectively. Limitations included the fact that the study was a single-arm study without a comparison group, technological improvements, changes in surgical protocol during the study, and the use of ADT to downsize the prostate in 39% of patients. ConclusionsHIFU is a potentially effective treatment of localized PCa, with a low PCa-specific mortality rate and a high MFSR at 10 yr as well as acceptable morbidity.

Sa1147 Efficacy of Second-Look Endoscopy After Endoscopic Hemostasis in Acute Peptic Ulcer Bleeding : Risk Factor Analysis of Recurrent Bleeding

G A A b st ra ct s stage IV. RESULTS: All pancreatic tumors were visualized by HIFU ultrasound monitor system. Treatment data in Stage III and IV were followed; mean tumor size was 31.8 vs 30.1 mm, mean treatment sessions: 2.6 vs 2.7 times, mean total treatment time: 2.7 vs 2.2 hours, mean total number of irradiation: 2801 vs 1769, respectively. There was no significant difference in treatment data between two groups. The effects of HIFU therapy in Stage III and IV were the following; the rate of complete tumor ablation was 87.5 vs 71.4%, the rate of symptom relief effect was 80 vs 56%, the effectiveness of primary lesion was CR:0, PR:2, SD:13, PD:1 vs CR:0, PR:2, SD:10, PD:2, and primary disease control rate (DCR) more than SD was 93.8% vs 78.6%. Mean survival time (MST) after HIFU therapy was 14.1 vs 7.2 month, respectively (p,0.01, p=0.0009). MST after diagnosis as PC was 32.4 vs 14.8 month, respectively (p,0.01, p=0.002). Combination therapy of HIFU with chemotherapy in Stage III was better result than common GEM single agent chemotherapy in our hospital. (MST: 14.9month). CONCLUSION: This study suggested that HIFU therapy has the potential of new method of combination therapy for non-metastatic PC.

581 HIFU therapy for castration-resistant prostate cancer

581 HIFU therapy for castration-resistant prostate cancer

HIFU in der Salvage Behandlung von Patienten mit Prostatakarzinom-Rezidiv nach primärer externer Bestrahlungstherapie – Status 2012

Patients with (local) recurrence of prostate cancer after radiation therapy face the question of the appropriate diagnostic and possible therapeutic options. Many patients in this setting receive palliative androgen deprivation therapy alone, with arguable impact on overall cancer survival. In the case of an isolated local recurrence, salvage prostatectomy represents a potentially curative therapeutic option, albeit with a high complication rate. Alternatively, these patients can be offered a local treatment with salvage HIFU therapy. Salvage HIFU therapy is based on the thermal ablation of tissue through high-intensity focused ultrasound. In addition, the formation of microbubbles (cavitation) and their implosion lead to an enhancement of tissue ablation. The results of 6 monocentric studies (2004-2011) with an overall number of 408 patients (22-167 patients) are presented and critically reviewed. The median follow-up was 18.71 months (7.4-39). The 3-year progression free survival (PFS) varied from 25% (D'Amico high risk) to 53% (D'Amico low-risk), the 5-year overall survival was 90%. The rate of urinary incontinence varied between 7 and 60% in all grades (grade III urinary incontinence 0-9.5%). In 22 cases surgical incontinence treatment was performed. 53 patients developed a urethral stricture or stenosis leading to surgical treatment. Urethral-rectal fistulae were seen in 0-7%. The current data on salvage HIFU can be evaluated as insufficient. The main criticisms can be seen in the lack of randomization, the monocentric and retrospective analyses of the data, the heterogeneous stratification of risk groups as well as inadequate definition of postinterventional treatment failure. The studies indicate that salvage HIFU therapy leads to a mid-term overall survival with complication rates that are comparable to those of other local salvage therapies. Randomized multicentric studies are needed to further validate the results of salvage HIFU therapy.

Cavitation micro-bubble behavior in ultrasound field for HIFU therapy enhancement

The incepted cavitation micro-bubbles at the target tissue are used to enhance tissue heating in High-Intensity Focused Ultrasound therapy. The control of the inertial cavitation is required to achieve the efficient tissue ablation. The high-intensity ultrasound is used to incept a cavitation, so that the duration time is short enough to prevent the tissue coagulation. The low-intensity ultrasound follows just after the high-intensity ultrasound to continuously drive the cavitating micro-bubbles and coagulate the tissue. Following the experiment, we simulate the focusing of ultrasounds through a mixture containing micro-bubbles with considering the size and number density distributions in space. The numerical simulation shows that the heating region coincides with the cavitation incepted region by high-intensity ultrasound where the micro-bubbles are remaining as cavitation nuclei. The numerical results elucidate well the experimental ones.

979 Localized prostate cancer control with primary HIFU therapy: Outcomes from 5663 men followed with the @-registry

979 Localized prostate cancer control with primary HIFU therapy: Outcomes from 5663 men followed with the @-registry

24 MR-directed selective HIFU therapy of prostate cancer using a TRUS guidance platform

24 MR-directed selective HIFU therapy of prostate cancer using a TRUS guidance platform

Preclinical Study of the Novel Vascular Occluding Agent, WST11, for Photodynamic Therapy of the Canine Prostate

Vascular targeted photodynamic therapy with WST09 shows promise for recurrent prostate cancer after radiation but hydrophobicity in aqueous solutions limited application. We tested the safety and efficacy of WST11, a novel water soluble vascular occluding agent, for vascular targeted photodynamic therapy of the dog prostate and compared it to WST09 vascular targeted photodynamic therapy. Optical fibers were inserted in the prostate and connected to diode lasers. WST11 (Steba Biotech, Cedex, France) at varying doses, including a drug control with no light in 34 dogs, and WST09 (Steba Biotech) (2 mg/kg) in 3 dogs were infused during 10 minutes. Illumination was initiated at 5 or 10 minutes, and lasted up to 33.2 minutes based on laser fluence and delivered energy. Blood was collected for analysis and pharmacokinetics. The end point was at 1 week. No vascular targeted photodynamic therapy associated change was observed in blood pressure or blood test values. Circulating WST11 increased with drug infusion and decreased rapidly during 1 hour to reach undetectable levels by 24 hours. All except 1 dog with bowel intussusception did well after vascular targeted photodynamic therapy with only mild urinary symptoms that resolved within 24 to 48 hours. Lung and liver were normal. Hemorrhage was present in all prostates except controls. This translated into necrosis at a WST11 threshold and within a window of doses at fixed illumination. Necrosis was associated with loss of the vessel endothelial layer. Fluence highly impacted necrosis. WST11 vascular targeted photodynamic therapy was advantageously comparable to WST09 vascular targeted photodynamic therapy, and optimally ablated about 5.0 cm(3) of tissue per lobe and about 10 cm(3) of the whole prostate. The safety and efficacy of WST11 vascular targeted photodynamic therapy in the dog prostate support clinical applications for prostate cancer and benign prostatic hyperplasia.