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Biomedical subjects

Michael Mullerad

Publications and source records attributed to Michael Mullerad.

17 recordsLinked to original sources

Imaging and therapy of malignant pleural mesothelioma using replication-competent herpes simplex viruses.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive cancer that is refractory to current treatment modalities. Oncolytic herpes simplex viruses (HSV) used for gene therapy are genetically engineered, replication-competent viruses that selectively target tumor cells while sparing normal host tissue. The localized nature, the potential accessibility and the relative lack of distant metastasis make MPM a particularly suitable disease for oncolytic viral therapy. METHODS: The infectivity, selective replication, vector spread and cytotoxic ability of three oncolytic HSV: G207, NV1020 and NV1066, were tested against eleven pathological types of MPM cell lines including those that are resistant to radiation therapy, gemcitabine or cisplatin. The therapeutic efficacy and the effect on survival of NV1066 were confirmed in a murine MPM model. RESULTS: All three oncolytic HSV were highly effective against all the MPM cell lines tested. Even at very low concentrations of MOI 0.01 (MOI: multiplicity of viral infection, ratio of viral particles per cancer cell), HSV were highly effective against MPM cells that are resistant to radiation, gemcitabine and cisplatin. NV1066, an oncolytic HSV that expresses green fluorescent protein (GFP), was able to delineate the extent of the disease in a murine model of MPM due to selective infection and expression of GFP in tumor cells. Furthermore, NV1066 was able to reduce the tumor burden and prolong survival even when treatment was at an advanced stage of the disease. CONCLUSION: These findings support the continued investigation of oncolytic HSV as potential therapy for patients with therapy-resistant MPM.

Animals↗

Functional sequelae of cavernous nerve injury in the rat: is there model dependency.

INTRODUCTION: The rat model of cavernous nerve (CN) injury has been developed in an effort to define the functional and structural consequences of neural trauma in the corpus cavernosum. However, there is no universally accepted method of inducing nerve injury in this model, with neurotomy and crush models being used currently. To address this issue, we induced CN injury using various techniques in an effort to compare the hemodynamic sequelae of these injuries. METHODS: Twenty-five adult male Sprague-Dawley rats were divided into five groups: (1) control: laparotomy only; (2) exposure: laparotomy and exposure of cavernous nerves bilaterally without nerve manipulation; (3) neurotomy; bilateral neurotomy; (4) bulldog crush: bilateral nerve crush with bulldog vascular clamp; and (5) hemostat nerve crush: bilateral nerve crush with a hemostat. Ten days later, a second operation was performed during which systemic mean arterial pressure (MAP) and intracavernosal pressure (ICP) were measured in response to CN stimulation proximal to the site of injury. Hemodynamic endpoints assessed included ICP/MAP ratio, rate of tumescence, and rate of detumescence. RESULTS: The ICP/MAP ratio (mean +/- 95% confidence interval) in the control group was 70 +/- 4%. ICP/MAP ratios were significantly reduced in all CN injury groups compared with control group: exposure: 41 +/- 10% (P < 0.001); neurotomy: 35 +/- 15% (P < 0.001); bulldog crush: 39 +/- 13% (P < 0.001); hemostat crush: 31 +/- 9% (P < 0.0001). No significant difference existed in ICP/MAP ratios between the injury groups. Of note, the exposure group also demonstrated significant functional alterations. The rates of tumescence and detumescence were significantly reduced in all groups compared with the control group. CONCLUSION: No significant difference in the magnitude and consistency of hemodynamic alterations has been demonstrated in all CN injury models assessed in this study.

Animals↗

Citation characteristics of basic science research publications in general surgical journals.

BACKGROUND: Basic science research (BSR) publications in general surgical (GS) journals are an important "translational bridge" for practicing surgeons and surgical trainees. The purpose of this study is to characterize the BSR publications in GS journals and to analyze their citation frequencies. METHODS: In 1996, all (224) BSR publications in the five highest rated U.S. GS journals (by impact factor) were reviewed, characterized, and their citation frequencies were compared to BSR publications in non-GS journals. RESULTS: On average, a BSR publication from these journals is cited 32 times (range 1-141, median 11). Half of the publications were cited more than 10 times in 6 years and 22% were cited twice, or more, within 1 year of publication. One in four publications were cited twice or more in journals with an impact factor greater than five. Citation frequencies of BSR publications in GS journals were related to the journal impact factor (P = 0.07), and to having a basic scientist (i.e., Ph.D.) as one of the authors (P < 0.01). Citation characteristics of BSR publications in GS journals were similar to those of BSR publications in non-GS journals with similar impact factors. CONCLUSIONS: We found that BSR publications in the U.S. GS journals studied had significant citation frequencies.

Biomedical Research↗

5-fluorouracil and gemcitabine potentiate the efficacy of oncolytic herpes viral gene therapy in the treatment of pancreatic cancer.

Oncolytic herpes viruses are attenuated, replication-competent viruses that selectively infect, replicate within, and lyse cancer cells and are highly efficacious in the treatment of a wide variety of experimental cancers. The current study seeks to define the pharmacologic interactions between chemotherapeutic drugs and the oncolytic herpes viral strain NV1066 in the treatment of pancreatic cancer cell lines. The human pancreatic cancer cell lines Hs 700T, PANC-1, and MIA PaCa-2 were treated in vitro with NV1066 at multiplicities of infection (MOI; ratio of the number of viral particles per tumor cell) ranging from 0.01 to 1.0 with or without 5-fluorouracil (5-FU) or gemcitabine. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Viral replication was measured using a standard plaque assay. Six days after combination therapy, 76% of Hs 700T cells were killed compared with 43% with NV1066 infection alone (MOI = 0.1) or 0% with 5-FU alone (2 micromol/L) (P < .01). Isobologram and combination-index analyses confirmed a strongly synergistic pharmacologic interaction between the agents at all viral and drug combinations tested (LD5 to LD95) in the three cell lines. Dose reductions up to 6- and 78-fold may be achieved with combination therapy for NV1066 and 5-FU, respectively, without compromising cell kill. 5-FU increased viral replication up to 19-fold compared with cells treated with virus alone. Similar results were observed by combining gemcitabine and NV1066. We have demonstrated that 5-FU and gemcitabine potentiate oncolytic herpes viral replication and cytotoxicity across a range of clinically achievable doses in the treatment of human pancreatic cancer cell lines. The potential clinical implications of this synergistic interaction include improvements in efficacy, treatment-associated toxicity, tolerability of therapeutic regimens, and quality of life. These data provide the cellular basis for the clinical investigation of combined oncolytic herpes virus therapy and chemotherapy in the treatment of pancreatic cancer.

Antineoplastic Agents↗

Comparison of nephron-sparing surgery in central versus peripheral renal tumors.

OBJECTIVES: To determine the feasibility of nephron-sparing surgery (NSS) in patients with centrally located tumors. METHODS: A retrospective cohort study of 118 patients who underwent NSS between 1993 and 2002 (35 patients with centrally located tumors and 83 with peripherally located tumors) was performed. Kaplan-Meier curves were constructed to evaluate freedom from local recurrence and disease-specific survival in patients with conventional histologic subtype tumors. The Wilcoxon test was used to compare the curves (two-tailed P < or =0.05 was considered to be statistically significant). RESULTS: Intraoperatively, in patients with centrally located tumors, the need to close the collecting system (P = 0.035) and for blood transfusions (P = 0.033) was greater. Two perioperative deaths occurred in patients with peripherally located tumors. Two patients with centrally located tumors subsequently underwent nephrectomy. Of the patients with centrally located tumors, 1 patient had a positive margin, 2 patients had local recurrence, and 1 patient developed metastasis. No positive surgical margins or local recurrence was found in patients with peripherally located tumors, although 4 patients developed distant metastasis. Kaplan-Meier curves for patients with conventional histologic subtype tumors demonstrated a statistically significant difference for local recurrence (P = 0.04), but not for survival (P = 0.71). The mean follow-up time was 38.8 and 43.8 months for patients with centrally located and peripherally located tumors, respectively. CONCLUSIONS: NSS can be used to postpone, or eliminate the need for, nephrectomy in 94.3% of patients with centrally located tumors and can achieve oncologic disease control similar to that for exophytic lesions. These data indicate that NSS should be considered even for patients with centrally located tumors, taking into account that performing such surgery is a challenging task.

Cohort Studies↗

Megameatus intact prepuce hypospadias variant: application of tubularized incised plate urethroplasty.

OBJECTIVES: The characteristics of the megameatus intact prepuce (MIP) hypospadias variant present a unique challenge to surgeons. Dissatisfaction with the results of conventional repair methods led to the emergence of several alternative surgical approaches, including the glanular approximation (GAP) and pyramid procedures. The application of tubularized, incised plate (TIP) urethroplasty has not been documented in this setting. METHODS: Twenty-four patients (mean age 18.5 months, range 6 to 60) presented with MIP. They had all been circumcised. The meatus was glanular in 6, coronal in 15, and distal shaft in 3 patients. Glanular MIP was repaired by meatal advancement and glanuloplasty (n = 2) or the GAP technique (n = 4). Coronal MIP was repaired by the GAP (n = 7) or TIP urethroplasty (n = 8), and distal shaft MIP was repaired by TIP urethroplasty (n = 3). Stents or catheters were used only with TIP urethroplasty. The mean follow-up period was 40 months (range 8 to 80). RESULTS: Satisfactory cosmetic and functional results were achieved in 20 patients (83%). The other 4 patients included 1 patient who underwent GAP and meatoplasty and 3 of the 11 patients who underwent TIP urethroplasty, of whom 2 underwent meatoplasty and 1 simple local repair of a urethrocutaneous fistula without the need for urethral reconstruction. CONCLUSIONS: The success rates for all selected techniques were satisfactory. TIP urethroplasty can be successfully used in the more severe, proximal forms of MIP.

Child, Preschool↗

Herpes simplex virus based gene therapy enhances the efficacy of mitomycin C for the treatment of human bladder transitional cell carcinoma.

PURPOSE: Oncolytic replication competent herpes simplex virus type-1 (HSV) mutants have the ability to replicate in and kill malignant cells. We have previously reported the ability of replication competent HSV to control bladder cancer growth in an orthotopic murine model. We hypothesized that the combination of a chemotherapeutic agent used for intravesical treatment, namely mitomycin C (MMC) (Bristol-Myers Squibb Oncology, Princeton, New Jersey), and oncolytic HSV would exert a synergistic effect for the treatment of human transitional cell carcinoma. MATERIALS AND METHODS: We used mutant HSV NV1066 (Medigene, San Diego, California), which is deleted for viral genes ICP0 and ICP4, and selectively infects cancer cells, to treat the transitional cell carcinoma lines KU19-19 and SKUB. Cell survival was determined by lactate dehydrogenase assay for each agent as well as for drug-viral combinations from days 1 to 5. The isobologram method and the combination index method of Chou-Talalay were used to assess the synergistic effect. RESULTS: NV1066 enhanced MMC mediated cytotoxicity at all combinations tested for KU19-19 and SKUB. The combination of the 2 agents demonstrated a synergistic effect and allowed dose reduction by 12 and 10.4 times (NV1066), and by 3 and 156 times (MMC) for the treatment of KU19-19 and SKUB, respectively, while achieving an estimated 90% cell kill. CONCLUSIONS: These data provide the cellular basis for the clinical investigation of combined MMC and oncolytic HSV therapy for the treatment of bladder cancer.

Antibiotics, Antineoplastic↗

Comparison of endorectal magnetic resonance imaging, guided prostate biopsy and digital rectal examination in the preoperative anatomical localization of prostate cancer.

PURPOSE: We compared the accuracy of endorectal magnetic resonance imaging (erMRI), transrectal ultrasound (TRUS) guided biopsy and digital rectal examination (DRE) for detecting the location of cancer in the prostate gland and seminal vesicles. MATERIALS AND METHODS: This is a retrospective study of 106 consecutive patients with prostate cancer who were referred for erMRI before radical prostatectomy. Step-section pathological data and erMRI were available in 90 patients, DRE data were available on 86 and individually labeled sextant core biopsies were available in 45. T1 and T2-weighted erMRI was interpreted by a single reader, who scored the likelihood of tumor on a 5-point scale in each seminal vesicle and in 12 locations in the prostate gland. MR spectroscopy data were not used for erMRI interpretation. One pathologist reviewed whole mount serial sections of radical prostatectomy specimens. The area under ROC curves was used to evaluate accuracy. RESULTS: The area under ROC curves for tumor localization was higher for erMRI than for DRE at the prostatic apex (0.72 vs 0.66), mid gland (0.80 vs 0.69) and base (0.83 vs 0.69). It was likewise higher for erMRI than for TRUS biopsy in the mid gland (0.75 vs 0.68) and base (0.81 vs 0.61) but not in the apex (0.67 vs 0.70). On mixed model analysis erMRI significantly increased the accuracy of prostate cancer localization by DRE or TRUS biopsy (each p <0.0001). CONCLUSIONS: For prostate cancer localization erMRI contributes significant incremental value to DRE or TRUS biopsy findings (each p <0.0001).

Biopsy↗

[Nephron sparing surgery as a treatment modality for renal angiomyolipoma].

OBJECTIVE: There is no consensus concerning the indications for active treatment (selective angioembolization (SAE) or surgery) versus observation alone, and the treatment modality for patients with renal angiomyolipoma (AML). Our study aimed to analyze the results of long-term follow-up of patients with renal AML treated by nephron-sparing surgery (NSS). MATERIALS AND METHODS: The medical records of thirteen patients with renal AML were retrospectively reviewed for clinical and histopathologic features. There were twelve women and one man (mean age 55 years) who were treated by NSS in our medical center between the years 1993-2001. RESULTS: One patient with tuberous sclerosis had bilateral multifocal tumors, another patient that presented with shock and retroperitoneal bleeding underwent an urgent NSS. Overall, eight patients were symptomatic at diagnosis. The mean tumor diameter was 5.5 cm (range 2.5-13 cm). There was no need to perform nephrectomy in any of the patients. Two patients had enucleation of more than one tumor in the same session. In one case the adrenal gland was surrounded by the AML and was removed with the specimen. No other serious complications were recorded. Four patients required blood transfusions. The mean follow-up period was 26 months (range: 6-62 months) and during that time there was no evidence of recurrence or decreased renal function. Only one patient developed AML in the contralateral kidney, there was one case of incisional hernia and another patient continued to suffer from flank pain. CONCLUSIONS: The results of the present study suggest that NSS is a safe and effective treatment modality for renal AML.

Adult↗

Prostate cancer: incremental value of endorectal MR imaging findings for prediction of extracapsular extension.

PURPOSE: To assess the incremental value of endorectal magnetic resonance (MR) imaging findings in addition to clinical variables for prediction of extracapsular extension (ECE) in patients with prostate cancer. MATERIALS AND METHODS: In this cohort study, 344 consecutive patients with biopsy-proved prostate cancer underwent endorectal MR imaging prior to surgery; 216 of these patients also underwent MR spectroscopic imaging. MR images were interpreted by 10 attending radiologists. The likelihood of ECE was scored retrospectively on the basis of MR imaging reports. Clinical variables included serum prostate-specific antigen (PSA) level, Gleason score, clinical stage of tumor, greatest percentage of cancer in all core biopsy specimens, percentage of cancer-positive core specimens in all core biopsy specimens, and presence of perineural invasion. For data analysis, receiver operating characteristic (ROC) curves and univariate and multivariate logistic regression analyses were used. Jackknife analysis was used for prediction of probability from a model that included clinical variables as tested comparatively with a model that included the clinical variables plus endorectal MR imaging findings. A difference with P <.05 was considered significant. RESULTS: At univariate analysis, all variables were associated with ECE. At ROC univariate analysis, endorectal MR imaging findings had the largest area under the ROC curve. At multivariate analysis, serum PSA level, percentage of cancer in all core biopsy specimens, and endorectal MR imaging findings (P =.001, P =.001, and P <.001, respectively) were predictors of ECE. Areas under ROC curve for two models, with and without endorectal MR imaging findings, were 0.838 and 0.772, respectively (P =.022). CONCLUSION: A model containing endorectal MR imaging findings has a significantly larger area under the ROC curve than a model containing only clinical variables; thus, endorectal MR imaging findings add incremental value in the prediction of ECE.

Adult↗

Prostate cancer: detection of extracapsular extension by genitourinary and general body radiologists at MR imaging.

PURPOSE: To determine whether predictive value of endorectal magnetic resonance (MR) imaging findings in detection of prostate cancer extracapsular extension (ECE) is significantly affected by the reader's subspecialty experience. MATERIALS AND METHODS: In this cohort study, 344 consecutive patients with biopsy-proved prostate cancer underwent endorectal MR imaging followed by surgery. Likelihood of ECE described in MR imaging reports was compared with clinical predictor variables. ECE was determined from the final pathologic report on specimens resected at surgery. Readers of MR images were classified into genitourinary MR imaging radiologists (n = 4) and general body MR imaging radiologists (n = 6). For data analysis, Wilcoxon rank sum and chi(2) tests, as well as receiver operating characteristic (ROC) curves and univariate and multivariate logistic regression analyses, were used. A difference with P <.05 was considered significant. RESULTS: Univariate analysis results demonstrated that all predictors except clinical stage were significantly associated with detection of ECE in both groups of readers (P <.05). In the genitourinary MR imaging radiologist group of patients, area under the ROC curve for endorectal MR imaging findings (0.833) was larger than areas under the curves for all other predictors (0.566-0.701). In the general body MR imaging radiologist group of patients, area under the ROC curve for endorectal MR imaging findings (0.646) was not larger than areas under the curves for all other predictors (0.582-0.793). Results of multivariate analysis of two models, one with all predictors and another with all predictors except endorectal MR imaging findings, demonstrated a significant increase in area under the ROC curve with endorectal MR images interpreted by genitourinary MR imaging radiologists (P =.019 and.31, respectively). CONCLUSION: Endorectal MR imaging findings are significant predictors for detection of ECE when MR images are interpreted by genitourinary radiologists experienced with MR imaging of the prostate.

Adult↗

Bladder cancer as a prognostic factor for upper tract transitional cell carcinoma.

PURPOSE: Upper tract transitional cell carcinoma (UTTCC) is a relatively rare tumor. Overall 5-year disease specific survival is in the range of 16.5% to 95% depending on stage. In this study we evaluated predictors associated with disease recurrence and disease specific survival. MATERIALS AND METHODS: We report on 129 patients with a median age of 68 years who underwent nephroureterectomy for UTTCC between July 1989 and June 2002. A total of 67 patients had primary UTTCC and 62 had previous (52) or synchronous (10) transitional cell carcinoma of the bladder (BTCC). Medical records were reviewed and analyzed for possible prognostic predictors (primary tumor stage, grade, multifocality, carcinoma in situ, symptoms and signs at presentation, sex, and history of smoking). Disease specific survival and freedom from bladder recurrence were assessed with the Kaplan-Meier method, and differences between the groups were compared using the log rank test. The Cox proportional hazards regression model was used to assess the significance of each predictor. RESULTS: Disease specific death was reported for 44 patients. In a multivariate analysis using previous BTCC as a predictor (categorized as superficial, invasive or none), primary disease stage and history of BTCC were associated with disease specific survival (p = 0.001 and p = 0.018). History of BTCC grouped the patients into distinct populations in terms of disease specific survival and freedom from bladder recurrence. CONCLUSIONS: This study demonstrates that a history of BTCC (invasive or superficial) has an adverse effect on the prognosis of patients diagnosed with UTTCC independent of primary tumor stage.

Adult↗

The value of quantitative 99M technetium dimercaptosuccinic acid renal scintigraphy for predicting postoperative renal insufficiency in patients undergoing nephrectomy.

PURPOSE: Radical nephrectomy is a routine urological practice. However, little is known about the use of dimercapto-succinic acid (DMSA) scan to evaluate compensatory changes after surgery and its ability to identify patient at risk for postoperative chronic renal failure or insufficiency. We predicted remaining kidney function using DMSA scan and serum creatinine. MATERIALS AND METHODS: A total of 42 patients were enrolled in the study. All underwent DMSA scan before surgery and in 38 DMSA scan was done after unilateral nephrectomy. Serum creatinine was determined before and 1 year after surgery. The Student t test was used to determine statistical significance. Spearman rank core analysis was used to evaluate the association of calculated creatinine clearance time after surgery and renal absolute uptake before surgery. We performed 1-way ANOVA comparison of the means to determine the influence of age distribution on kidney hypertrophy and the increase in kidney uptake. RESULTS: Average patient age was 61.5 years. Baseline mean creatinine clearance time was 71.5 ml. per minute, which decreased to 58.6 ml. per minute after nephrectomy (p <0.0001). Before surgery DMSA scan of the remaining kidney demonstrated an absolute uptake of 4.2% higher than that in the resected kidney (13.5% versus 9.35%, p = 0.0008). After nephrectomy the remaining kidney had an average increase of 3.9% of mean absolute uptake (17.7% versus 13.8%, p = 0.0001). Spearman rank core analysis demonstrated an association of higher preoperative absolute uptake in the remaining kidney with postoperatively high creatinine clearance time (r = 0.458, p = 0.003). Furthermore, 75% of patients with postoperative creatinine clearance time less than 40 ml. per minute presented with a preoperative absolute uptake of lower than 11% in the remaining kidney. In contrast, 75% of those with a postoperative creatinine clearance time of higher than 40 ml. per minute had a preoperative absolute uptake of higher than 11%. CONCLUSIONS: A preoperative absolute uptake of lower than 11% in the remaining kidney was a significant risk factor for postoperative chronic renal insufficiency.

Adult↗

[The role of nephron sparing surgery for renal cancer].

AIM: A contemporary review of the indications, techniques and outcome of the nephron sparing surgical approach in the management of solid renal masses. MATERIAL AND METHODS: Pertinent articles were reviewed using the MEDLINE. RESULTS: Nephron sparing surgery is increasingly being used to treat patients with solid renal lesions. The technical success rate of nephron sparing surgery is excellent, and operative morbidity and mortality are low. For renal cell carcinoma, long-term cancer-free survival is comparable to radical nephrectomy, particularly in patients with low stage disease. The reported incidence of multifocal renal cell carcinoma is approximately 15%, and it depends on tumor size, histology and stage. The risk of multifocal disease is low (less than 5%), when the maximal diameter of the primary tumor is 4 cm or less. Minimally invasive modalities of tumor resection or destruction show promising results, however they should be reserved for selected patients and await improvement in technology. Only when long-term follow-up data is available these methods might become routine clinical practice. CONCLUSIONS: Nephron sparing surgery provides effective therapy for patients in whom preservation of renal function is a relevant clinical consideration. Accumulating data in appropriately selected patients suggest a long-term functional advantage gained by the maximal preservation of unaffected renal parenchyma without sacrificing cancer control.

Carcinoma, Renal Cell↗

Bladder tumor antigen stat test in non-urothelial malignant urologic conditions.

BACKGROUND: The bladder tumor antigen stat is a simple and fast one-step immunochromatographic assay for the detection of bladder tumor-associated antigen in urine. OBJECTIVES: To evaluate the BTA stat in non-bladder cancer patients in order to identify the categories contributing to its low specificity. METHODS: A single voided urine sample was collected from 45 patients treated in the urology clinic for conditions not related to bladder cancer. Each urine sample was examined by the BTA stat test and cytology. RESULTS: The overall specificity of the BTA stat test was 44%, which was significantly lower than that of urine cytology, 90%. The false positive rates for the BTA stat test varied among the different clinical categories, being highest in cases of urinary tract calculi (90%), and benign prostatic hypertrophy (73%). Exclusion of these categories from data analysis improved BTA stat specificity to 66%. CONCLUSIONS: Clinical categories contributing to low BTA stat specificity can be identified, and their exclusion improves the specificity of this test.

Antigens, Neoplasm↗

Use of positron emission tomography to target prostate cancer gene therapy by oncolytic herpes simplex virus.

Herpes simplex virus (HSV) oncolytic gene therapy is a promising treatment modality against cancer. We have demonstrated that androgen-induced cellular changes enhance oncolytic viral replication and improve efficacy in the treatment of androgen-dependent prostate cancer cell line. Imaging of changes in 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake by positron emission tomography (PET) is a sensitive method of detecting altered cellular metabolism involved in cancer therapy. We therefore hypothesized that FDG-PET can predict tumor response to oncolytic HSV therapy. In this study, androgen increased cell kill (74%) in vitro and enhanced viral yield (2.4-fold) in vivo following HSV therapy. This enhanced efficacy was predicted by high FDG accumulation in intact animals compared to low FDG uptake following orchiectomy (p = 0.002). This proof-of-concept study provides the mechanistic basis for selecting patients for targeted oncolytic viral therapy by means of a noninvasive molecular imaging method in the treatment of prostate cancer.

Animals↗