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We assessed the incidence rate and management impact of oligometastatic disease detected onWe retrospectively reviewed our clinical database for men with PCA who underwentWe identified 21 patients with oligometastases upon first BCR (PSA 0.2-56.8 ng/mL) out of 89 eligible patients. There was a significant difference (p = 0.04) in the mean PSA levels between patients with local recurrence (n = 12) and those without local recurrence (n = 9). In the subgroup of analysis of patients without local recurrence, there was no significant association between mean PSA level and number of oligometastases (p = 0.83). Distribution of oligometastases included 66.7% isolated nodal disease and 33.3% bone only. Twelve (57.1%) patients had change in management to include change in ADT, salvage therapy, or both. Treatment change was initiated in 62.5%, 28.6%, 66.7%, 100%, and 100% of patients with 1, 2, 3, 4, and 5 oligometastatic lesions, respectively.The incidence rate of oligometastatic disease in men with first BCR of PCA undergoing

Background F-Fluciclovine is the most recent prostate cancer (PCa)-directed PET radiotracer approved by the US Food and Drug Administration for detection of recurrent PCa. We report the treatments and outcomes of patients at our institution with PCa recurrences detected on F-fluciclovine PET/CT. Methods We identified men with recurrent PCa detected on F-fluciclovine PET/CT performed between 2017 and 2018 who were previously treated definitively and analyzed their patterns of care and cancer-specific outcomes. Results We identified 28 men with recurrent PCa detected on F-fluciclovine PET/CT. Twenty-three were initially treated with surgery and 13 also received postoperative radiation therapy (RT). Five patients were initially treated with definitive radiation. After surgery, the median time to F-fluciclovine PET/CT was 67 months (median prostate-specific antigen [PSA] of 1.63 ng/mL). After RT, the median time to F-fluciclovine PET/CT was 95 months with median PSA of 13.31 ng/mL. Six men recurred locally, 9 recurred in the pelvic nodes, 9 had distant nodal recurrences, and 4 had osseous metastases. Of the patients initially treated with surgery, 4 received salvage radiation and 3 received androgen deprivation therapy (ADT). Of the patients initially treated with surgery and postoperative RT, 3 received salvage pelvic nodal dissection, 4 received salvage radiation, and 2 received ADT. Of the patients initially treated with radiation, 4 received salvage ADT. All had PSA decline after salvage therapy. Conclusions F-fluciclovine PET/CT can localize PCa recurrences, and subsequent salvage therapies appear effective with decreasing PSA. Longer follow-up will reveal if these diagnostic tests and subsequent therapies will improve PCa survival.

The theranostics concept using the same target for both imaging and therapy dates back to the middle of the last century, when radioactive iodine was first used to treat thyroid diseases. Since then, radioiodine has become broadly established clinically for diagnostic imaging and therapy of benign and malignant thyroid disease, worldwide. However, only since the approval of SSTR2-targeting theranostics following the NETTER-1 trial in neuroendocrine tumors, and the positive outcome of the VISION trial has theranostics gained substantial attention beyond nuclear medicine. The roll-out of radioligand therapy for treating a high-incidence tumor such as prostate cancer requires the expansion of existing and the establishment of new theranostics centers. Despite wide global variation in the regulatory, financial and medical landscapes, this guide attempts to provide valuable information to enable interested stakeholders to safely initiate and operate theranostic centers. This enabling guide does not intend to answer all possible questions, but rather to serve as an overarching framework for multiple, more detailed future initiatives. It recognizes that there are regional differences in the specifics of regulation of radiation safety, but common elements of best practice valid globally.

Metastatic castration resistant prostate cancer (mCRPC) is incurable. The expression of the transmembrane protein prostate-specific membrane antigen (PSMA) is markedly increased in most mCRPC lesions. PSMA has been recognized as a viable biologic target for imaging and radionuclide therapy (theranostics) in mCRPC. The PET agents (68)Ga-PSMA-11 and (18)F-DCFPyL have recently been approved for imaging evaluation of patients with suspected metastasis who are candidates for initial definitive therapy and patients with suspected recurrence based on elevated serum prostate-specific antigen level. Radioligand therapy (RLT) with (177)Lu-PSMA-617 ((177)Lu-vipivotide tetraxetan, Pluvicto, Novartis/AAA) was approved on March 23, 2022, based on the favorable results of the VISION trial. It has been recognized that PET imaging of PSMA expression and glucose metabolism (with (18)F-FDG) provides a more comprehensive assessment of the tumor burden and heterogeneity. However, there are many unresolved issues that surround whether or not imaging with (18)F-FDG PET is advantageous in the clinical setting of PSMA RLT in mCRPR.

A 51-year-old man diagnosed with high-grade, high-volume metastatic castration-sensitive prostate adenocarcinoma received pelvic radiation, androgen deprivation therapy, and intravenous docetaxel. Serum prostate-specific antigen became undetectable following treatment. Within a year, his cancer progressed to castration-resistant disease, and he was treated with oral abiraterone acetate 1000 mg and prednisone 10 mg daily. Despite this, the serum prostate-specific antigen rose from 0.03 to 1.39 μg/L, and F-DCFPyL and F-FDG PET/CT showed progression. While F-DCFPyL uptake may be seen in aggressive disease, F-FDG portends poor prognosis. Despite intravenous platinum-based chemotherapy, the patient died of respiratory failure 20 months after his initial diagnosis.

OBJECTIVE. The purpose of this study is to provide a concise summary of the current experience with (68)Ga-labeled prostate-specific membrane antigen (PSMA)–11 imaging of prostate and nonprostate malignancies and benign conditions. CONCLUSION. PSMA is overexpressed in prostate cancer and in the neovasculature of many other malignancies. The relevance of PSMA as a biologic target, coupled with advances in the design, synthesis, and evaluation of PSMA-based radionuclides for imaging and therapy, is anticipated to play a major role in patient care.

PURPOSE: The aims of this study were to report on our initial experience using (18)F-fluciclovine PET/CT to detect recurrent prostate carcinoma in patients with low serum prostate-specific antigen (PSA) after definitive treatment of primary disease and to conduct a preliminary investigation for factors associated with positive scan findings. PATIENTS AND METHODS: In this retrospective study, (18)F-fluciclovine PET/CT scans from 28 men with suspected recurrence of prostate carcinoma and PSAvalues of 1 ng/mL or less were examined to identify the site(s) of disease recurrence. Differences in detection rate for Gleason scores of 7 and greater than 7, T2 and T3 disease, negative and positive surgical margins, and negative and positive seminal vesicle invasion were compared using the Fisher exact test. Mean PSA and mean PSA doubling time of patients with positive scans and negative scans were compared using the independent 2-group t test. RESULTS: At least one site of disease recurrence was identified in 13 (46.4%) of 28 patients. Disease detection rate was significantly higher in patients with history of Gleason score greater than 7 (Fisher exact test, P = 0.004). Mean PSA and PSA doubling time were not significantly different between patients with positive and negative (18)F-fluciclovine PET/CT scans (P = 0.29 and 0.70, respectively). CONCLUSIONS: Detection of recurrent prostate cancer using (18)F-fluciclovine PET/CT is possible in patients with low but rising PSA levels of 1 ng/mL or less. In such patients, local and nodal recurrences are more common than distant metastasis, and Gleason score greater than 7 is associated with positive scan results.

Progress in unraveling the complex biology of cancer, novel developments in radiochemistry, and availability of relevant α-emitters for targeted therapy have provided innovative approaches to precision cancer management. The approval of 223Ra dichloride for treatment of men with osseous metastatic castrate-resistant prostate cancer unleashed targeted α-therapy as a safe and effective cancer management strategy. While there is currently active research on new α-therapy regimens for prostate cancer based on the prostate-specific membrane antigen, there is emerging development of radiopharmaceutical therapy with a range of biological targets and α-emitting radioisotopes for malignancies other than the prostate cancer. This article provides a brief review of preclinical and first-in-human studies of targeted α-therapy in the cancers of brain, breast, lung, gastrointestinal, pancreas, ovary, and the urinary bladder. The data on leukemia, melanoma, myeloma, and neuroendocrine tumors will also be presented. It is anticipated that with further research the emerging role of targeted α-therapy in cancer management will be defined and validated.

Twenty-five years ago, oligometastatic disease was proposed as an intermediary clinical state of cancer with unique implications for therapies that may impact cancer evolution and patient outcome. Identification of limited metastases that are potentially amenable to targeted therapies fundamentally depends on the sensitivity of diagnostic tools, including new-generation imaging methods. For men with biochemical recurrence after definitive therapy of the primary prostate cancer, PET/CT using either the FDA-approved radiolabeled amino acid analogue

Approximately 5% of patients with cutaneous squamous cell carcinoma (CSCC) may develop recurrent or metastatic disease. The management of such cases is challenging and requires multi-disciplinary care. Immunotherapy using PD-1 inhibition was approved to treat unresectable or metastatic CSCC in 2018. Given limited data regarding clinical outcomes outside of published trials, we describe our experience using this therapy.We retrospectively reviewed all patients treated with PD-1 inhibition as therapy for locally advanced, regionally metastatic or distant metastatic CSCC at the University of Southern California. Clinicopathological characteristics, treatment data using PD-1 inhibitors, and outcomes were assessed.Among 26 patients treated with PD-1 inhibition, the objective response rate was 42.3%, with 19.2% of patients having partial response and 23.1% having complete response to therapy. The median progression-free survival was 5.4 months. Median tumor mutational burden (TMB) was higher among responders compared to non-responders (60 vs. 9 Mut/Mb, p = 0.04). Primary CSCC tumor location on the head/neck was also associated with response to PD-1 inhibition (p = 0.04). Two patients with mutations affecting mismatch repair deficiency were noted to have complete response to treatment. No other variables were associated with treatment outcomes.PD-1 inhibition produces durable responses among patients with advanced or metastatic CSCC. PD-1 inhibition therapy is well tolerated, but patients should be monitored closely for immune-related adverse events, particularly frail or immune-suppressed patients. Further investigation of potential biomarkers to help identify patients who will derive the most benefit from this therapeutic option is needed.

PURPOSE Provide evidence- and expert-based recommendations for optimal use of imaging in advanced prostate cancer. Due to increases in research and utilization of novel imaging for advanced prostate cancer, this guideline is intended to outline techniques available and provide recommendations on appropriate use of imaging for specified patient subgroups. METHODS An Expert Panel was convened with members from ASCO and the Society of Abdominal Radiology, American College of Radiology, Society of Nuclear Medicine and Molecular Imaging, American Urological Association, American Society for Radiation Oncology, and Society of Urologic Oncology to conduct a systematic review of the literature and develop an evidence-based guideline on the optimal use of imaging for advanced prostate cancer. Representative index cases of various prostate cancer disease states are presented, including suspected high-risk disease, newly diagnosed treatment-naïve metastatic disease, suspected recurrent disease after local treatment, and progressive disease while undergoing systemic treatment. A systematic review of the literature from 2013 to August 2018 identified fully published English-language systematic reviews with or without meta-analyses, reports of rigorously conducted phase III randomized controlled trials that compared ≥ 2 imaging modalities, and noncomparative studies that reported on the efficacy of a single imaging modality. RESULTS A total of 35 studies met inclusion criteria and form the evidence base, including 17 systematic reviews with or without meta-analysis and 18 primary research articles. RECOMMENDATIONS One or more of these imaging modalities should be used for patients with advanced prostate cancer: conventional imaging (defined as computed tomography [CT], bone scan, and/or prostate magnetic resonance imaging [MRI]) and/or next-generation imaging (NGI), positron emission tomography [PET], PET/CT, PET/MRI, or whole-body MRI) according to the clinical scenario.

Imaging is often used to evaluate men with biochemical recurrence (BCR) of prostate cancer after definitive primary treatment (radical prostatectomy [RP] or radiotherapy [RT]). The goal of imaging is to identify the source of elevated or rising serum prostate-specific antigen (PSA) levels because

OBJECTIVE. This article reviews recent developments in targeted radionuclide therapy (TRT) approaches directed to malignant liver lesions, bone metastases, neuroendocrine tumors, and castrate-resistant metastatic prostate cancer and discusses challenges and opportunities in this field. CONCLUSION. TRT has been employed since the first radioiodine thyroid treatment almost 75 years ago. Progress in the understanding of the complex underlying biology of cancer and advances in radiochemistry science, multimodal imaging techniques including the concept of “see and treat” within the framework of theranostics, and universal traction with the notion of precision medicine have all contributed to a resurgence of TRT.

A novel recombinant disintegrin, vicrostatin (VCN), displays high binding affinity to a broad range of human integrins in substantial competitive biological advantage over other integrin-based antagonists. In this study, we synthesized a new (64)Cu-labeled VCN probe and evaluated its imaging properties for prostate cancer in PC-3 tumor bearing mice. Macrocyclic chelating agent 1,8-diamino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]-eicosine (DiAmSar) was conjugated with PEG unit, and followed by a coupling with VCN. The precursor was then radiolabeled with positron emitter (64)Cu (t(1/2) = 12.7h) in ammonium acetate buffer to provide (64)Cu-Sar-PEG-VCN, which was subsequently subject to in vitro studies, small animal PET, and biodistribution studies. The PC-3 tumor targeting efficacy of (64)Cu-Sar-PEG-VCN was compared to a cyclic RGD peptide based PET probe ((64)Cu-Sar-RGD). (64)Cu labeling was achieved in 75% decay-corrected yield with radiochemical purity of >98%. The specific activity of (64)Cu-Sar-PEG-VCN was estimated to be 37 MBq/nmol. MicroPET imaging results showed that (64)Cu-Sar-PEG-VCN has preferential tumor uptake and good tumor retention in PC-3 tumor xenografts. As compared to (64)Cu-Sar-RGD, (64)Cu-Sar-PEG-VCN produces higher tumor-to-muscle (T/M) imaging contrast ratios at 2 h (4.66 ± 0.34 vs. 2.88 ± 0.46) and 24 h (4.98 ± 0.80 vs. 3.22 ± 0.30) post-injection (pi), and similar tumor-to-liver ratios at 2 h (0.43 ± 0.09 vs. 0.37 ± 0.04) and 24 h (0.57 ± 0.13 vs. 0.52 ± 0.07) pi. The biodistribution results were consistent with the quantitative analysis of microPET imaging, demonstrating good T/M ratio (2.73 ± 0.36) of (64)Cu-Sar-PEG-VCN at 48 h pi in PC-3 tumor xenografts. For both microPET and biodistribution studies at 48 h pi, the PC-3 tumor uptake of (64)Cu-Sar-PEG-VCN is lower than that of (64)Cu-Sar-RGD. (64)Cu-Sar-PEG-VCN has the potential for in vivo imaging of prostate cancer with PET, which may provide a unique non-invasive method to quantitatively localize and characterize prostate cancer.

Accurate appraisal of treatment response in metastatic castrate-resistant prostate cancer (mCRPC) is challenging in view of remarkable tumor heterogeneity and the available choices among many established and novel therapeutic approaches. The purpose of this single-center prospective study was to evaluate the comparative prognostic utility of PERCIST 1.0 in predicting overall survival (OS) in patients with mCRPC compared to RECIST 1.1 and prostate-specific antigen (PSA)-based treatment response assessments. Methods: Patients with mCRPC were prospectively enrolled if they were beginning systemic medical therapy or transitioning to new systemic therapy after not responding to a prior treatment. All patients underwent a baseline 18F-fluorodeoxyglucose (FDG) positron emission tomography/ computed tomography (PET/CT) prior to the initiation of treatment and again 4 months after the start of therapy. Patients' responses to treatment at 4 months compared to baseline were evaluated with RECIST 1.1, PERCIST 1.0 and PSA response criteria. The associations between patients' response categories and OS were evaluated. OS was defined as the duration in time between the date of baseline PET/CT to death from any cause. Patients with different response status were compared with logrank tests. Survival probabilities were calculated using the Kaplan-Meier method. Results: Patients with progressive disease by PSA response criteria at 4 months demonstrated significantly shorter OS (24-month OS probability: 18% ± 11%) compared to patients with stable disease, SD, (44% ± 19%, p=0.03) and complete response, CR, or partial response, PR, (53% ± 11%, p=0.03). RECIST 1.1 response criteria demonstrated a similar trend in OS, however no statistically significant differences were noted between patients with PD (25% ± 15%) compared to SD/non-CR, non-PD (54% ± 13%) and CR/PR (54% ± 14%) (p=0.13). PERCIST 1.0 criteria demonstrated significant differences in OS between responders, CMR/PMR (56% ± 12%), compared to SMD (38% ± 17%, p=0.03) and PMD (21% ± 10%, p=0.01). Patients with progressive disease by both PERICST 1.0 and PSA response criteria demonstrated significantly worse OS (24-month OS: 0%, 12-month OS: 31% ± 14%) compared to patients with progressive disease by either response criteria. Conclusion: PERCIST 1.0 may provide significant prognostic information for patients with mCRPC undergoing systemic chemotherapy, particularly when incorporated with PSA treatment response criteria.

Background: National Comprehensive Cancer Network guidelines consider 18F-fluciclovine PET-CT for prostate cancer biochemical recurrence localisation after radical prostatectomy, whereas European Association of Urology guidelines recommend prostate-specific membrane antigen (PSMA) PET-CT. To the best of our knowledge, no prospective head-to-head comparison between these tests has been done so far. The aim of this study was to compare prospectively paired 18F-fluciclovine and PSMA PET-CT scans for localising biochemical recurrence of prostate cancer after radical prostatectomy in patients with low prostate-specific antigen (PSA) concentrations (

The aim of this prospective investigation was to assess the association of (18)F-FDG PET/CT with time to hormonal treatment failure (THTF) in men with metastatic castration-sensitive prostate cancer. Methods: 76 men with metastatic castration-sensitive prostate cancer recruited from 2005 to 2011 underwent (18)F-FDG PET/CT and were followed prospectively for THTF, defined as treatment change to chemotherapy or death. Patients who had not switched to chemotherapy were censored at the last follow-up date (median of 36 mo; range, 12–108 mo). Cox regression analyses were performed to examine the association between PET/CT measurements: sum of SUV(max), maximum SUV(max), and average SUV(max) for up to 10 of the most active lesions and THTF. Survival probabilities were based on the Kaplan–Meier method. Results: 43 patients had hormonal treatment failure, and 8 died without documented treatment failure. Median THTF was 26.5 mo (95% confidence interval [CI], 15.5–46.6 mo). The THTF-free probability at 5 y was 35% ± 6%. On univariate analysis, all PET parameters, including number of lesions, were statistically significant for THTF. In a reduced multivariate model accounting for clinical variables, only sum of SUV(max) (hazard ratio, 1.01; 95% CI, 1.002–1.03; P = 0.024) and number of lesions (hazard ratio, 1.18; 95% CI, 1.08–1.29; P < 0.001) were independently associated with THTF. When sum of SUV(max) was grouped into quartile ranges, there was a significantly worse survival probability for patients in the fourth-quartile range than in the first, with a univariate hazard ratio of 6.2 (95% CI, 2.8–13.6; P < 0.001). Conclusion: Sum of SUV(max) and number of lesions derived from (18)F-FDG PET/CT provide independent prognostic information on THTF in men with metastatic castration-sensitive prostate cancer.

Integrated positron emission tomography/computed tomography (PET/CT) with 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)F-FDG) has emerged as a powerful tool for the combined metabolic and anatomic evaluation of many cancers. In urological oncology, however, the use of (18)F-FDG has been limited by a generally low tumor uptake, and physiological excretion of FDG through the urinary system. (18)F-FDG PET/CT is useful when applied to specific indications in selected patients with urological malignancy. New radiotracers and positron emission tomography/magnetic resonance imaging (PET/MRI) are expected to further improve the performance of PET in uro-oncology.

Prostate cancer is a prevalent public health problem worldwide. While imaging has played a major role in this disease, there still remain many challenges and opportunities. Positron emission tomography with various physiologically based radiotracers is fundamentally suited to interrogate this biologically and clinically heterogeneous disease along the course of its natural history. In this article, I review briefly the published evidence for the use of positron emission tomography with 18F-fluorodeoxyglucose, 11C-acetate, and 18F- or 11C-choline in the imaging evaluation of prostate cancer. Although the focus of the article will be on these radiotracers given the accumulated experience with them, but I will also comment on the outlook for the use of other emerging PET radiotracers such as those targeted to the prostate-specific membrane antigen and the amino acid metabolism pathway. It is anticipated that PET will play major role in the evaluation of prostate cancer in the current evidence-based medicine environment. There will also be exciting novel prospects for the use of therapeutic-diagnostic (theransotic) pairs in the management of patients with prostate cancer.

Background A remarkable therapeutic efficacy has been demonstrated with 225Ac-prostate-specific membrane antigen (PSMA)-617 in heavily pre-treated metastatic castration-resistant prostate cancer (mCRPC) patients. We report our experience with 225Ac-PSMA-617 therapy in chemotherapy-naïve patients with advanced metastatic prostate carcinoma. Methods Seventeen patients with advanced prostate cancer were selected for treatment with 225Ac-PSMA-617 in 2-month intervals, with initial activity of 8 MBq, then de-escalation to 7 MBq, 6 MBq or 4 MBq in cases of good response. In one patient, activity was escalated to 13 MBq in the third cycle. Fourteen patients had three treatment cycles administered, while in three patients treatment was discontinued after two cycles due to good response. Six out of 17 patients received additional treatments after the third cycle. Prostate-specific antigen (PSA) was measured every 4 weeks for PSA response assessment. 68Ga-PSMA-PET/CT was used for functional response assessment before each subsequent treatment cycle. Serial full blood count, renal function test, and liver function were obtained to determine treatment-related side effects. Results Good antitumor activity assessed by serum PSA level and 68Ga-PSMA-PET/CT was seen in 16/17 patients. In 14/17 patients, PSA decline ≥90% was seen after treatment, including seven patients with undetectable serum PSA following two (2/7) or three cycles (5/7) cycles of 225Ac-PSMA-617. Fifteen of 17 patients had a > 50% decline in lesions avidity for tracer on 68Ga-PSMA-PET/CT including 11 patients with complete resolution (PET-negative and either stable sclerosis on CT for bone or resolution of lymph node metastases) of all metastatic lesions. Grade 1/2 xerostomia was seen in all patients, and none was severe enough to lead to discontinuation of treatment. One patient had with extensive bone marrow metastases and a background anemia developed a grade 3 anemia while another patient with solitary kidney and pre-treatment grade 3 renal failure developed grade 4 renal toxicity following treatment. The group presented with significant palliation of bone pain and reduced toxicity to salivary glands due to de-escalation. Conclusions 225Ac-PSMA-617 RLT of chemotherapy-naïve patients with advanced metastatic prostate carcinoma led to a ≥ 90% decline in serum PSA in 82% of patients including 41% of patients with undetectable serum PSA who remained in remission 12 months after therapy. The remarkable therapeutic efficacy reported in this study could be achieved with reduced toxicity to salivary glands due to de-escalation of administered activities in subsequent treatment cycles. This necessitates further exploration for informing clinical practice and clinical trial design.

Primary bone malignancies are characterized with anatomic imaging. However, in recent years, there has been an increased interest in PET/computed tomography scanning and PET/MRI with fludeoxyglucose F 18 for evaluating and staging musculoskeletal neoplasms. These hybrid imaging modalities have shown promise largely owing to their high sensitivity, ability to perform more thorough staging, and ability to monitor treatment response. This article reviews the current role of PET/computed tomography scanning and PET/MRI in primary malignancies of bone, with an emphasis on imaging characteristics, clinical usefulness, and current limitations.

PURPOSE: (18)F-fluciclovine is a synthetic amino acid radiotracer that has recently been approved in Europe and the United States for positron emission tomography (PET) imaging in men with biochemical recurrence (BCR) of prostate cancer following prior definitive treatment. Accurate identification of the sites of disease in patients presenting with BCR of prostate cancer is important in determining the appropriate treatment. Bone is the most frequent site of metastatic disease in patients with prostate cancer. METHODS: We conducted a comprehensive review of the available preclinical and clinical data on the diagnostic performance of (18)F-fluciclovine PET-computed tomography (PET/CT) in an attempt to draw practical and general conclusions on the utility and limitations of (18)F-fluciclovine PET/CT in localization of osseous metastatic disease in prostate cancer. RESULTS: The cumulative preclinical data and results of some retrospective and two prospective clinical studies suggest that (18)F-fluciclovine can detect early bone marrow involvement in patients with BCR of prostate cancer and negative prior bone specific imaging findings. CONCLUSIONS: (18)F-Fluciclovine PET/CT appears to offer useful information for early detection of bone metastases in men with BCR of prostate cancer. Additional investigations will be needed to compare the diagnostic performance of (18)F-fluciclovine PET/CT to other standard and novel imaging methods in initial staging, BCR and castrate-resistant phases of disease.

Gastrin-releasing peptide receptors (GRPRs), part of the bombesin (BBN) family, are aberrantly overexpressed in many cancers, including those of the breast, prostate, pancreas, and lung, and therefore present an attractive target for cancer diagnosis and therapy. Different bombesin analogs have been radiolabeled and used for imaging diagnosis, staging, evaluation of biochemical recurrence, and assessment of metastatic disease in patients with prostate cancer. Recently, interest has shifted from BBN-like receptor agonists to antagonists, because the latter does not induce adverse effects and demonstrate superior in vivo pharmacokinetics. We review the preclinical and clinical literatures on the use of GRPRs as targets for imaging and therapy of prostate cancer, with a focus on the newer developments and theranostic potential of GRPR peptides.

We assessed the association between the presence and absence of androgen on the normal biodistribution of the positron emission tomography (PET) cellular proliferation imaging biomarker, [Non-castrated (n=4) and castrated (n=4) athymic non-tumor-bearing male mice served as models for presence and absence, respectively, of androgen. MicroPET-CT scans were performed 1 h following tail vein administration of 200 uCi ofPre-pellet baseline average SUVThere is a significant modulatory effect of androgen on normal

The utility of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in prostate cancer depends on the phase of the disease along the natural history of this prevalent malignancy in men. Incidental high FDG uptake in the prostate gland, while rare, should prompt further investigation with at least a measurement of serum prostate specific antigen (PSA) level. While in general FDG uptake level may significantly overlap among normal, benign, and malignant tissues, aggressive primary tumors with Gleason score greater than 7 tend to display high FDG uptake. PET with FDG may be useful in staging of those patients with aggressive primary tumors and can localize the site of disease in a small fraction of men with biochemical failure and negative conventional imaging studies. FDG PET may be quite useful in treatment response assessment and prognostication of patients with castrate-resistant metastatic prostate cancer.

1338 Objectives: Differentiated thyroid cancer (DTC) patients with elevated or rising serum thyroglobulin (Tg) levels and multiple other negative conventional imaging studies represent a clinically difficult group of patients. 99m Tc-sestamibi is a non-conventional imaging study for DTC that was used in the 1980s-1990s to help evaluate DTC patients before being replaced with 18F-FDG. However, 18F-FDG PET scans may also be negative in these patients. This is a preliminary analysis of our study to evaluate the diagnostic use of 99mTc-sestamibi scans to identify the source of elevated or rising Tgs in patients with negative conventional imaging including negative 18F-FDG PET scans. Methods This prospective study included DTC patients who were at least 18 years old, had at least one prior 131I therapy, and had elevated Tg>5 ng/ml or positive anti-Tg antibodies (TgAb). In addition, all of the following imaging studies must have been clinically reported as negative for recurrence or metastasis within the last 12 months: neck ultrasound, diagnostic radioiodine scan, chest x-ray, CT of the chest/abdomen with/without contrast, and 18F-FDG PET/CT. If other imaging studies were performed, such as bone scans or brain imaging, these must also have been read as negative. This study was approved by the IRB at MedStar Health and all participants signed informed consent. Participants were injected with 925 MBq (25 mCi) of 99mTc-sestamibi intravenously and whole body images were acquired after ~1h with acquisition speed 4cm/min with parallel-hole low-energy collimator. Extra spot view, pinhole view, or SPECT/CT images were performed when necessary. Two blinded nuclear medicine physicians independently interpreted the 99mTc-sestamibi images, and graded each foci 1-5 (1 = definite physiological uptake or artifact; 2 = most likely physiological uptake or artifact; 3 = indeterminate; 4 = most likely recurrence or metastasis; 5 = definite recurrence or metastasis). Discordant findings were resolved by consensus. Foci graded 3-5 were categorized as positive result and was followed-up for confirmation. Results A total of four patients completed the sestamibi scan to date. One out of four patients (Patient1) was positive on the sestamibi scan for distant metastasis. In Patient 1, the sestamibi whole-body posterior image demonstrated abnormal focal uptake in the right posterior calvarium and corresponding to an occipital lytic bone lesion on the SPECT/CT (Figure 1). The patient underwent surgical resection of the skull metastasis, and pathology confirmed metastatic thyroid cancer. Five months post-surgery the suppressed Tg was markedly reduced and stable at ~3.2ng/ml. Table 1 shows the sestamibi scan results, subsequent management and follow-up. With confirmation of the location of the metastatic foci in Patient 1, the two negative 18F-FDG PET/CT that were previously performed one year apart were reviewed again. The radiology reports did not document interpretation of the low-dose localization CT. In retrospect, the lytic skull metastasis was visible on both of the head CT, but could have been easily missed on the PET due to the normal intensive brain 18F-FDG activity. Conclusions In this preliminary analysis, 99mTc-sestamibi was able to identify the source of elevated Tg levels in one out of four DTC patients with biochemical recurrence and negative conventional imaging studies. 99mTc-sestamibi may have a role in thyroid cancer localization when physical exam, neck ultrasound, radioiodine scan, chest/abdomen CT, and 18F-FDG PET/CT could not identify. Additional patients are being recruited. Research Support We are grateful for the generous donations from our patients.

We report on an incidental detection of a meningioma on [(18)F]-2′-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil ((18)F-FMAU) PET/CT scan that was performed during a prospective investigation of (18)F-FMAU PET/CT for targeted biopsy of potential sites of tumor in men with suspected prostate cancer based on elevated prostate specific antigen level. Neither prostate multiparamteric MRI nor (18)F-FMAU PET/CT localized small volume Gleason 3+3 tumor deposits. However, an incidental focal high accumulation of (18)F-FMAU was observed in high right parietal lobe that displayed characteristics of a meningioma on a subsequent brain MRI.

Molecular imaging is paving the way for precision and personalized medicine. In view of the significant biologic and clinical heterogeneity of prostate cancer, molecular imaging is expected to play an important role in the evaluation of this prevalent disease. The natural history of prostate cancer spans from an indolent localized process to biochemical relapse after radical treatment with curative intent to a lethal castrate-resistant metastatic disease. The ongoing unraveling of the complex tumor biology of prostate cancer uniquely positions molecular imaging with PET to contribute significantly to every clinical phase of prostate cancer evaluation. The purpose of this article was to provide a concise review of the current state of affairs and potential future developments in the diagnostic utility of PET in prostate cancer.

The lifetime risk of prostate cancer in developed countries is about 1 in 6 men (1). In the post–prostate-specific antigen (PSA) screening era, most patients (about 93%) present with locoregional disease, whereas metastatic disease is the initial presentation in about 4% of patients, with the remaining 3% categorized as of unknown stage (1). Although men with localized prostate cancer are treated with curative intent, many will eventually develop biochemical recurrence and metastatic disease (2). Most men with metastatic prostate cancer develop a castrate-resistant state having a hallmark of tumor growth despite castrate levels of serum androgens (3). Castrate-resistant metastatic prostate cancer is incurable and is the main cause of disease-related morbidity and mortality. An important unmet need in this clinical context is the optimal selection and sequencing of various drug options guided by the most informative outcome measures to provide maximum benefit to individual patients (4). Given the proclivity of prostate cancer to metastasize to bone, and the limitations of existing imaging tools for assessment of bone metastases, evaluating response quantitatively has been difficult. These difficulties include the inability to use response criteria such as Response Evaluation Criteria in Solid Tumors for assessment of bone metastases on CT, the confounding effect of the flare phenomenon on standard bone scintigraphy, and the ambiguity associated with the clinical significance of changes in serum PSA level (5,6). This notion is also coupled with the current evolution in the treatment paradigm to control, relieve, or eliminate disease manifestations (e.g., PSA, imaging findings, or symptoms) and to delay or prevent future disease manifestations (7). A recognized and relevant outcome measure in castrate-resistant metastatic prostate cancer is overall survival (OS), which may be useful for guiding and optimizing treatment decisions. OS may be predicted by several clinical, laboratory, and imaging parameters. However, given the remarkable heterogeneity of disease in terms of prognosis, a quantitative patient-specific imaging-based predictive model of OS will be of significant clinical value. PET is an ideal imaging tool for noninvasive interrogation of the underlying tumor biology. Several promising radiotracers are being investigated in the imaging evaluation of prostate cancer, including 18F- or 11C-choline, 18F- or 11C-acetate, 16β-18F-fluoro-5α-dihydrotestosterone targeted to the androgen receptor, the synthetic L-leucine analog anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid, and PSMA-based PET radiotracers (8,9). However, the exact diagnostic and prognostic roles of these radiotracers in prostate cancer are undefined and will require continued investigation. 18F-FDG is the most common PET radiotracer used for oncologic applications and is based on elevated glucose metabolism in malignant tissue in comparison to normal tissue. 18F-FDG uptake in prostate cancer depends on tumor differentiation, with low uptake in well-differentiated tumors and high uptake in aggressive poorly differentiated tumors (10). Cumulative current evidence strongly suggests that 18F-FDG PET/CT may be useful in the imaging evaluation of men with metastatic prostate cancer (10). The aim of this prospective investigation was to determine whether parameters derived from 18F-FDG PET/CT bear independent prognostic information on OS in patients with castrate-resistant prostate cancer.

Purpose This study aims to determine a velocity threshold in the main renal vein (MRV) of renal transplants and evaluate the cause and clinical significance of elevated velocity. Methods Maximum MRV velocity from 331 consecutive renal transplant Doppler ultrasounds in 170 patients was recorded. A priori, twice the median MRV velocity was selected as the threshold for elevation. Ultrasounds were divided into “early” and “late” periods based on time after transplantation. Charts were reviewed for outcomes associated with elevated MRV velocity. Endpoints included graft failure or death. Serum creatinine (Cr) levels among groups were compared, and temporal changes in MRV velocity were plotted. Results A ≥70 cm/s was chosen as the threshold for elevated MRV velocity. Graft failure and complication/intervention rates were higher only in the “late” group with elevated MRV velocity. There was no association between elevated MRV velocity and death, no predilection for a particular biopsy result, and no difference in Cr levels among groups. The majority of elevated velocities occurred during the immediate postoperative period and resolved without intervention. Conclusions Elevated MRV velocity in the early postoperative period is a transient phenomenon not correlating with outcome or requiring intervention. In the late period, elevated MRV velocity is associated with entities including hydronephrosis, perinephric collections, and arteriovenous fistulae.

Although selective metabolic and receptor-based molecular agents will surely be included in the future of prostate cancer diagnosis and therapy, currently available inorganic compounds-such as 18F-NaF for the diagnosis of bony disease and 223RaCl2 for the therapy of bone metastases-were recently shown to be superior to standard 99mTc-phosphonates for diagnosis and 153Sm-ethylenediaminetetramethylene phosphonate or 89SrCl2 for therapy. The advantages of 18F-NaF include improved lesion detection and, when used in combination with CT, improved diagnostic confidence and specificity. In addition to being the first approved α-emitter, 223RaCl2 is the first radiopharmaceutical to show an increase in overall survival, a decrease in skeletal events, palliation of bone pain, and a low profile of adverse reactions (which are mild and manageable). The management of metastatic bone disease with 223RaCl2 is uniquely satisfying, as patients can be monitored directly during their monthly treatment visits.

Imaging of the Warburg effect, which is the principal but not the sole cause for enhanced glucose metabolism in tumors, with PET and 18F-FDG has become the mainstay for the imaging evaluation of several cancers. Despite the seemingly prevalent notion that 18F-FDG PET may not be useful in prostate cancer, relatively limited evidence suggests that this imaging modality can be useful for the evaluation of the extent of metastatic disease and the assessment of the therapy response and prognosis in men with castration-resistant prostate cancer. Incidental high focal 18F-FDG uptake in the prostate gland, although generally rare, may also indicate occult prostate cancer that may need to be further scrutinized. In general, 18F-FDG PET is not useful for initial staging and is of limited utility in the clinical setting of biochemical failure after prior definitive therapy for primary cancer. Although more experience is needed, it appears that the imaging of cellular proliferation with PET and 3'-deoxy-3'-18F-fluorothymidine or 2'-18F-fluoro-5-methyl-1-β-d-arabinofuranosyluracil may also allow for targeted biopsy and localization for focal therapy of aggressive prostate tumors as well as assessment of the therapy response to various standard and novel treatment regimens in patients with metastatic disease.

OBJECTIVE. Recent advances in the fundamental understanding of the complex biology of prostate cancer have provided an increasing number of potential targets for imaging and treatment. The imaging evaluation of prostate cancer needs to be tailored to the various phases of this remarkably heterogeneous disease. CONCLUSION. In this article, I review the current state of affairs on a range of PET radiotracers for potential use in the imaging evaluation of men with prostate cancer.

Prostate cancer is the most common cancer and the second leading cause of cancer death affecting men in the United States.1 Despite successful treatments for localized prostate cancer, up to 40% of men will eventually (most within 10 y from primary treatment) experience a detectable rise in the serum prostate-specific antigen (PSA) level (biochemical failure), suggesting that prostate cancer can metastasize early in the course of the disease.2 However, biochemical failure may occur years before metastases become clinically evident, and the clinical course can be markedly different. The stratification of men with biochemical recurrence is an important unmet clinical need. Conventional imaging evaluation with CT and 99mTc-based bone scintigraphy (BS) may be negative or indeterminate in a substantial number of men with biochemical failure. 111In-capromab pendetide (ProstaScint; EUSA Pharma, Inc, Langhorne, Pa), which is a radiolabeled antibody targeted at the prostate-specific membrane antigen, has low sensitivity for detecting osseous metastases and poor specificity, making it of limited clinical value.3 More sensitive and specific imaging procedures may provide valuable information because treatment options are primarily based on detection and location of disease, for instance, observation in the absence of frank metastases, and the use of bone-targeted therapy for bone metastases. There is an increasing interest in the potential role of PET in prostate cancer. Several promising radiotracers are currently being investigated in the imaging evaluation of prostate cancer including 18F- or 11C-choline, 18F- or 11C-acetate, 16β-18F-fluoro-5α -dihydrotestosterone, targeted to the androgen receptor, anti–1-amino-3-18F-fluorocyclobutane-1-carboxylic acid, a synthetic l-leucine analog, and prostate-specific membrane antigen–based PET radiotracers.4 However, the contribution of these radiotracers to decision-making in prostate cancer remains undefined, and this will require continued investigation. 18F-FDG is the most common PET radiotracer used for oncologic applications. The ability of 18F-FDG PET to detect cancer is based on elevated glucose metabolism in malignant tissue in comparison to that in normal tissue.5 Current literature suggests that 18F-FDG PET/CT may be useful in the imaging evaluation of men with metastatic prostate cancer.6 Similarly, 18F-NaF PET/CT offers significantly higher sensitivity and specificity for identifying bone metastases in comparison to 99mTc-based BS.7,8 Recent decision by the Center for Medicare and Medicaid Services to reimburse sites participating in the National Oncologic PET Registry for 18F-NaF PET/CT scans has facilitated use of this sensitive imaging method in patients with cancer.9 There is lack of data regarding the potential utility of 18F-NaF and 18F-FDG PET/CT in men with biochemical recurrence of prostate cancer, who have negative conventional imaging studies. In view of the current critical need for early and accurate localization of occult metastatic disease in biochemical failure of prostate cancer, we set out to perform a prospective evaluation of 18F-NaF and 18F-FDG PET/CT imaging in this population.

Retinal degenerations trigger the loss of photoreceptors and cause the remaining de-afferented neural retina to undergo remodeling. Concerns over this potential retinal synaptic reorganization following visual loss have raised questions regarding the usefulness of visual restoration via retinal electrical stimulation. We have used quantitative positron emission tomography (PET) and 2-deoxy-2-[18F]fluoro-d-glucose (FDG) to objectively evaluate the connection between the retina and the primary visual cortex under both light and transcorneal electrical stimulation (TcES) in five subjects with retinal degeneration (RD) who have had more than ten years of light-perception-only best visual acuity and five age-matched normal-sighted controls. All subjects underwent quantitative PET with FDG as the metabolic tracer during stimulation of the right eye under both light stimulation condition and transcorneal electrical stimulation (TcES) using ERG-Jet contact lens electrode. Cortical activation maps from each stimulation condition were obtained using statistical parametric mapping. TcES phosphene threshold current and qualitative visual cortex activation from both stimulation conditions were compared between the two subject groups. Average phosphene threshold current was 0.72 ± 0.18 mA for the five normal-sighted controls and 3.08 ± 2.01 mA for the retinal degenerative subjects. Phosphene threshold current was significantly higher in retinal degenerative subjects compared to normal-sighted controls (p < 0.05). We found both light stimulation and TcES resulted in retinotopically mapped primary visual cortex activation in both groups. In addition, the patterns of early visual area activation between the two subject groups are more similar during TcES than light stimulation. Our findings suggest primary visual cortex continues to maintain its retinotopy in RD subjects despite prolonged visual loss.

Retinal activation via transcorneal electrical stimulation (TcES) in normal humans was investigated by comparing subject perception, model predictions, and brain activation patterns. The preferential location of retinal stimulation was predicted from 3-D admittance modeling. Visual cortex activation was measured using positron emission tomography (PET) and (18)F-fluorodeoxyglucose (FDG). Two different corneal electrodes were investigated: DTL-Plus and ERG-Jet. Modeling results predicted preferential stimulation of the peripheral, inferior, nasal retina during right eye TcES using DTL-Plus, but more extensive activation of peripheral, nasal hemiretina using ERG-Jet. The results from human FDG PET study using both corneal electrodes showed areas of visual cortex activation that consistently corresponded with the reported phosphene percept and modeling predictions. ERG-Jet was able to generate brighter phosphene percept than DTL-Plus and elicited retinotopically mapped primary visual cortex activation. This study demonstrates that admittance modeling and PET imaging consistently predict the perceived location of electrically elicited phosphenes produced during TcES.

Prostate cancer is biologically and clinically a heterogeneous disease that makes imaging evaluation challenging. The role of imaging in prostate cancer should include diagnosis, localization, and characterization (indolent vs. lethal) of the primary tumor, determination of extracapsular spread, guidance and evaluation of local therapy in organ-confined disease, staging of locoregional lymph nodes, detection of locally recurrent and metastatic disease in biochemical relapse, planning of radiation treatment, prediction and assessment of tumor response to salvage and systemic therapy, monitoring of active surveillance and definition of a trigger for definitive therapy, and prognostication of time to hormone refractoriness in castrate disease and overall survival. To address these tasks effectively, imaging needs to be tailored to the specific phases of the disease in a patient-specific, risk-adjusted manner. In this article, I review the preclinical and clinical evidence on the potential and emerging role of PET with the 3 most commonly studied radiotracers in prostate cancer, namely 18F-FDG, 18F- or 11C-acetate, and 18F- or 11C-choline.

Prostate cancer poses a major public health problem, particularly in the US and Europe, where it constitutes the most common type of malignancy among men, excluding nonmelanoma skin cancers. The disease is characterized by a wide spectrum of biological and clinical phenotypes, and its evaluation by imaging remains a challenge in view of this heterogeneity. Imaging in prostate cancer can be used in the initial diagnosis of the primary tumor, to determine the occurrence and extent of any extracapsular spread, for guidance in delivery and evaluation of local therapy in organ-confined disease, in locoregional lymph node staging, to detect locally recurrent and metastatic disease in biochemical relapse, to predict and assess tumor response to systemic therapy or salvage therapy, and in disease prognostication (in terms of the length of time taken for castrate-sensitive disease to become refractory to hormones and overall patient survival). Evidence from animal-based translational and human-based clinical studies points to a potential and emerging role for PET, using 18F-fluorodeoxyglucose as a radiotracer, in the imaging evaluation of prostate cancer.

We determined the glucose metabolism and computed tomographic (CT) density of the normal prostate gland in relation to age and prostate size on [F-18] fluorodeoxyglucose positron emission tomography (PET)-CT.We determined the CT density (Hounsfield Units, HU) and glucose metabolism (standardized uptake value, SUV) of the normal prostate in 145 men (age range 22-97 years) on PET-CT scans which were performed for indications unrelated to prostate pathology. Correlations among SUV, HU, prostate size, and age were calculated using Pearson's correlation coefficients, scatter plots, and linear regression trend lines. The SUV and HU values were also compared among different primary cancer types using the Kruskal-Wallis test.The population average and range of the normal prostate size were 4.3 +/- 0.5 cm (mean +/- SD) and 2.9-5.5 cm, respectively. The population average of mean and maximum CT densities was 36.0 +/- 5.1 HU (range 23-57) and 91.7 +/- 20.1 HU (range 62-211), respectively. The population average of mean and maximum SUV was 1.3 +/- 0.4 (range 0.1-2.7) and 1.6 +/- 0.4 (range 1.1-3.7), respectively. Mean SUV tended to decrease as the prostate size increased (r = -0.16, P = 0.058). Higher mean HU was correlated with higher mean SUV (r = 0.18, P = 0.033). The strongest association was observed between age and prostate size. The prostate gets larger as age increases (r = 0.32, P0.001). Prostate mean SUV, max SUV, mean HU, and max HU were not significantly different among different types of primary cancers.Although the normal prostate size increases with age, it does not significantly affect the gland's metabolism and CT density, and therefore age-correction of these parameters may be unnecessary.

Objectives We retrospectively assessed the diagnostic utility of dedicated positron emission tomography (PET) and hybrid PET-computed tomography (CT) scans with [F-18]fluorodeoxyglucose (FDG) in the imaging evaluation of patients with known or suspected recurrent and metastatic cholangiocarcinoma. Methods The study group included 24 patients (13 males and 11 females; age range, 34-75 years) with known or suspected recurrent and metastatic cholangiocarcinoma. We performed 8 dedicated PET scans (Siemens 953/A, Knoxville, Tenn) in 8 patients and 24 hybrid PET-CT scans (Siemens Biograph, Knoxville, Tenn) in 16 patients. Four patients underwent both pretreatment and posttreatment scans. Nonenhanced CT transmission scans were obtained for attenuation correction after administration of oral contrast material. PET images were obtained 60 minutes after the intravenous administration of 15 mCi (555 MBq) FDG. Prior treatments included surgery alone in 12 patients, surgery and chemotherapy in 6 patients, and surgery and combined chemoradiation therapy in 6 patients. Diagnostic validation was conducted through clinical and radiologic follow-up (2 months to 8 years). Results PET and CT were concordant in 18 patients. PET-CT correctly localized a hypermetabolic metastatic lesion in the anterior subdiaphragmatic fat instead of within the liver and was falsely negative in intrahepatic infiltrating type cholangiocarcinoma. PET was discordant with CT in 6 patients. PET was negative in an enlarged right cardiophrenic lymph node on CT, which remained stable for 1 year. In 1 patient, PET-CT scan showed hypermetabolic peritoneal disease in the right paracolic gutter without definite corresponding structural abnormalities, which was subsequently confirmed on a follow-up PET-CT scan performed 6 months after the initial study, at which time peritoneal nodular thickening was evident on concurrent CT. PET-CT documented the progression of locally recurrent and metastatic disease in another patient based on interval appearance of several new hypermetabolic lesions and significant increase in the standardized uptake values of the known lesions despite little interval change in the size and morphologic character of lesions on concurrent CT. It was also helpful in excluding metabolically active disease in patients with contrast enhancement at either surgical margin of hepatic resection site or focally within hepatic parenchyma and in an osseous lesion. Overall, based on the clinically relevant patient basis for detection of recurrent and metastatic cholangiocarcinoma, the sensitivity and specificity of PET (alone and combined with CT) were 94% and 100% and, for CT alone, were 82% and 43%, respectively. Conclusions FDG PET and PET-CT are useful in the imaging evaluation of patients with cholangiocarcinoma (except for infiltrating type) for detection of recurrent and metastatic disease and for assessment of treatment response. In particular, the combined structural and metabolic information of PET-CT enhances the diagnostic confidence in lesion characterization.

We report our 1-year postapproval clinical experience with Radium-223 dichloride for treatment of castrate-resistant prostate cancer with bone metastases.The clinical courses of the first 25 patients treated were reviewed retrospectively. Incidence of hematologic, gastrointestinal, and other adverse events were identified, including those events that led to cessation or delay in treatment. Alterations in bone pain and serum alkaline phosphatase and prostate-specific antigen (PSA) levels were evaluated.Six patients received all 6 scheduled doses of Radium-223 dichloride, 2 completed 5 doses, 6 received 4 doses, 2 completed 3 doses, 6 patients had 2 doses, and 3 patients received one dose, for a total of 91 doses administered. Nine patients discontinued treatment after receiving at least one dose due to progressive disease, 5 required blood transfusions, 5 developed gastrointestinal symptoms, 4 reported worsening bone pain, and 1 developed dermatitis. Downward trends in serum alkaline phosphatase and PSA were seen in 11 and 5 patients, respectively.About one-quarter of cohort completed the entire six-dose treatment. Advancing soft tissue disease was the primary reason for cessation of therapy. The adverse events were mild and manageable. A decline in serum alkaline phosphatase was more common than a decline in PSA.

Molecular imaging with PET using an increasing list of biologically relevant radiotracers is paving the way for precision and personalized medicine in prostate cancer ([1][1]). Prostate-specific membrane antigen (PSMA) has received a resurgence of attention as a useful biomarker in the imaging

Accurate prediction and assessment of relevant outcomes is important in clinical trial design and in clinical practice for selecting and sequencing appropriate individualized management of patients with prostate cancer. There have been many standard non-imaging based prediction tools for the various phases of prostate cancer. However these tools may be limited in individual cases and need updating based on the improved understanding of the underlying complex biology of the disease and the emergence of the novel targeted molecular imaging methods. A new platform of automated predictive tools that combine the independent molecular, imaging, and clinical information can contribute significantly to patient care and improve outcome. Such platform will also be of interest to regulatory agencies and payers as more emphasis is placed on supporting those interventions that have quantifiable and significant beneficial impact on patient outcome.

We evaluated the clinical utility of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG)–positron emission tomography (PET)/computed tomography (CT) on the precise localization of pathologic foci and exclusion of normal variants in the imaging evaluation of patients with esophageal carcinoma. Combined PET/CT scans were performed in 60 patients (50 males, 10 females, age range 47–84 years) with history of esophageal carcinoma either at the time of initial diagnosis (group I, n = 14) or for surveillance and/or detection of recurrent and metastatic disease (group II, n = 46). Prior treatments included esophagectomy with gastric pull-up (n = 23), surgery and chemotherapy (n = 3), surgery and chemoradiation therapy (n = 10), chemotherapy alone (n = 5), radiation therapy alone (n = 2), and chemoradiation without surgery (n = 3). Diagnostic validation was by tissue sampling in three patients and clinical/radiological follow-up for up to 1.5 years in the remaining patients. In group I, discordant abnormalities were noted in seven patients. PET demonstrated hypermetabolism in normal-size lymph nodes on CT in three patients that were considered likely true positive in view of concurrent existence of other adjacent enlarged hypermetabolic lymph nodes in the same nodal basin. Hypometabolic incidental CT abnormalities of up to 1-cm lung nodules were noted in three patients and pleural effusion in one patient, which were considered true negative in view of no change on follow-up PET/CT studies. In group II, both PET and CT showed concordant abnormalities in 23 patients. The precise image fusion of hypermetabolism in a liver lesion allowed a diagnostic CT-guided biopsy in one patient. PET demonstrated true positive hypermetabolic abnormalities in four patients that localized to structures, which were normal by noncontrast CT criteria, and true negative in one patient with hepatic fatty deposits. PET showed decline in metabolic activity of the primary lesion in one patient after chemotherapy, while the corresponding CT abnormality remained unchanged. PET/CT image fusion provided relevant complementary diagnostic information in 14 patients with discordant findings (23% of total) that resulted in biopsy in three cases, institution of chemotherapy in four cases, and a wait-and-watch strategy in seven cases. In conclusion, our findings add to the current body of literature that suggests that FDG-PET/CT scanning may improve the imaging evaluation of patients with esophageal cancer by providing complementary structural-metabolic information. In particular, our findings support the notion that PET/CT may be the most appropriate imaging modality in the evaluation of patients of esophageal cancer that may impact patient management.

Diagnostic imaging has played a major role in the evaluation of patients with the cancers of the reproductive tract. The imaging modalities have included ultrasonography, computed tomography, magnetic resonance imaging, hysterosalpingography, and scintigraphy with radiolabeled monoclonal antibodies. Positron emission tomography (PET) with [F-18]fluorodeoxyglucose also has been shown to be useful in the imaging evaluation of these patients. Clinical applications have included initial staging and posttherapy restaging of disease, detecting metastatic disease, differentiating posttherapy anatomic alterations from recurrent or residual disease, and predicting and evaluating treatment response. In this article, we review the diagnostic utility of dedicated PET and combined PET-computed tomography systems in the imaging assessment of reproductive tract malignancies (excluding prostate cancer) in both sexes with an emphasis on fluorodeoxyglucose applications.

We assessed the pattern of metabolic activity in the colon of subjects who received oral contrast and had no known or suspected colonic disease.Positron emission tomography/computed tomography (PET/CT) with [F-18]-fluorodeoxyglucose was performed in 50 patients with cancer and no known or suspected colonic pathology. Studies with intense focal or segmental colonic activity (in comparison to liver reference activity), which are known to be predictive of colonic pathology were excluded. Retrospectively, colon was divided into cecum, ascending, transverse, descending, and rectosigmoid partitions, and the corresponding volumetric regions of interest were drawn on all relevant CT images. Partitioned colonic maximum standardized uptake values (SUVmax) were compared using Wilcoxon rank-sum test. Frequency of occurrence for the various colonic uptake rank orders was also tabulated.For colonic partitions, range and median SUVmax, respectively, were in decreasing order: rectosigmoid (1.5-9.9, 2.9), cecum (1.2-6.3, 2.6), ascending (0.7-4.0, 1.8), transverse (0.4-4.1, 1.2), and descending (0.6-3.1, 1.2). The SUVmax at different colonic partitions were significantly different from each other (P0.001), except for the SUVmax between descending and transverse colonic segments (P=0.77). Combining the latter segments, the uptake rank order of "rectosigmoidcecumascending" was demonstrated in 50% and "cecumrectosigmoidascending" in 30% of subjects.Rectosigmoid and cecum tend to demonstrate higher metabolism than other colonic segments in the majority subjects who receive oral contrast during [F-18]-fluorodeoxyglucose positron emission tomography/CT and have no known or suspected colonic pathology.

Medical oncology is moving toward personalized and precision treatments. This evolution is spearheaded by ongoing discoveries on the fundamental machinery that controls tumor and hosts microenvironment biological behavior. α-Particles with their high energy and short range had long been recognized as potentially useful in the treatment of cancer. More than a century after the discovery of radium by the Curies, 223Ra dichloride is now available in the expanding armamentarium of therapies for metastatic castration-resistant prostate cancer. This advance occurs in the context of several other novel therapeutics in advanced prostate cancer that include more effective androgen receptor pathway inhibition, better chemotherapy, and immunotherapy. We present a concise review on the therapeutic use of 223Ra dichloride in this clinically important setting including excerpts on the radium history, physical properties, the alpharadin in symptomatic prostate cancer clinical trial, and practical information on its use in the clinic. It is anticipated that, with the current emergence of 223Ra as a viable form of therapy, interest in and use of α-particle therapy in the management of cancer will grow.

We evaluated 10 patients with suspected recurrent papillary thyroid cancer using [18F]fluorodeoxyglucose positron emission tomography (FDG PET). Prior therapy included total (n = 8) or subtotal (n = 2) thyroidectomy, radiation therapy (n = 2) and radioiodine ablation (n = 2). All patients had an 131I scan and one or more of the following imaging studies: 99Tcm-sestamibi scan. 111In-octreotide scan, sonography (US), computed tomography (CT) and magnetic resonance imaging (MRI). Both the PET and 131I scans were negative in four patients. The PET and 131I scan results were discordant in six patients. Of the six discordant cases, five had true-positive PET scans and false-negative 131I studies. Three of these patients underwent neck lymph node dissection that showed positive histology for metastatic papillary carcinoma. Another patient had fine-needle aspiration (FNA) of a parapharyngeal mass that was also positive for papillary carcinoma. One patient was treated with radiation to the thyroid surgical bed based on an elevated serum thyroglobulin and a positive PET finding. Tumour response with a decrease in the size of the lesion was documented by a follow-up MRI scan. The remaining patient had a presumed false-positive PET scan, since a difficult hypocellular FNA of a small palpable lymph node was negative for tumour. We conclude that FDG PET is useful in the evaluation of patients with suspected recurrent papillary thyroid cancer when the 131I scan is negative.