An Ultra-Rapid Biosensory Point-of-Care (POC) Assay for Prostate-Specific Antigen (PSA) Detection in Human Serum.

Prostate-specific antigen (PSA) is the established routine screening tool for the detection of early-stage prostate cancer. Given the laboratory-centric nature of the process, the development of a portable, ultra rapid high-throughput system for PSA screening is highly desirable. In this study, an advancedpoint-of-care system for PSA detection in human serum was developed based on a cellular biosensor where the cell membrane was modified by electroinserting a specific antibody against PSA. Thirty nine human serum samples were used for validation of this biosensory system for PSA detection. Samples were analyzed in parallel with a standard immunoradiometric assay (IRMA) and an established electrochemical immunoassay was used for comparison purposes. They were classified in three different PSA concentration ranges (0, <4 and ≥4 ng/mL). Cells membrane-engineered with 0.25 µg/mL anti-PSA antibody demonstrated a statistically lower response against the upper (≥4 ng/mL) PSA concentration range. In addition, the cell-based biosensor performed better than the immunosensor in terms of sensitivity and resolution against positive samples containing <4 ng/mL PSA. In spite of its preliminary, proof-of-concept stage of development, the cell-based biosensor could be used as aninitiative for the development of a fast, low-cost, and high-throughput POC screening system for PSA.

Performance and safety profile of regadenoson myocardial perfusion imaging: first experience in Greece.

OBJECTIVE: MPI can provide valuable information in the investigation of patients with known or suspected coronary artery disease. The stress component of the studies can be conducted with regadenoson, which was approved for clinical use in Greece in 2016. We investigated the performance and safety profile of regadenoson MPI based on our 7 months institutional experience. PATIENTS AND METHODS: We studied 96 consecutive patients (59 males, 37 females, mean age 70.35y.o, range: 46-87y.o.) referred to our department for a clinically indicated MPI study with pharmacological stress. Eleven patients suffered from chronic obstructive pulmonary disease. Patients underwent regadenoson stress test, combined with both stress and rest imaging. Data on the symptoms and electrocardiographic changes due to regadenoson administration were recorded. Symptoms were graded as 1-mild: a symptom that did not distress the patient, 2-moderate: a symptom that distressed the patient but it was self-limiting, or 3-severe: a symptom that distressed the patient requiring medical intervention. RESULTS: Regadenoson-related symptoms were reported in 56 patients and were: dyspnea, discomfort, dizziness, chest pain, epigastric pain, neck pain, headache, flushing, nausea, heartburn, weakness, and upper limbs numbness. The severity of symptoms was recorded as grade 1 in 30 patients, grade 2 in 25 patients, and grade 3 in 1 patient. Two or more different symptoms were reported in 28 patients. Ischemic electrocardiographic changes and arrhythmias were observed in 8 patients. CONCLUSION: Our findings support previously published data indicating the optimal safety profile of regadenoson MPI, even in the group of patients suffering from chronic obstructive pulmonary disease.

Scoring systems of quantitative bone scanning in prostate cancer: historical overview, current status and future perspectives.

Whole-body bone scintigraphy using technetium-99m-methylene-diphosphonate ((99m)Tc-MDP) is the most widely used radionuclide imaging modality applied in patients with prostate cancer. With this technique, the choice of methods to estimate the extend of the metastatic disease on the skeletal system includes various different approaches, classified in two main categories: First, the quantitative measurements of tracer uptake, defined either as the percentage of the injected dose of tracer, or as the more complicated plasma clearance techniques and second, the various semi-quantitative scoring systems of the bone scan images. These scoring systems can be based either on visual counting of bone lesions, or on the estimation of a numerical index that expresses the fractional involvement of each bone by tumour, called "Bone Scan Index" (BSI); the latter can be produced either visually (manually) or by the more sophisticated techniques of fully- or semi-automated (computerized) forms. In this review, a brief chronological overview of the aforementioned methods is presented, along with the main advantages, drawbacks and the prognostic implications of each method. There remains, however, the challenge of defining, developing and validating the optimal measurement methodology in order these scoring systems to obtain a wider clinical use.

Predictive implications of bone turnover markers after palliative treatment with (186)Re-HEDP in hormone-refractory prostate cancer patients with painful osseous metastases.

PURPOSE: To prospectively evaluate the predictive value of various bone formation and resorption markers in patients with bone metastases from prostate cancer after palliative treatment with (186)Re-1,1-hydroxyethylidene diphosphonate ((186)Re-HEDP). METHODS: Included in the study were 36 men with prostate cancer, suffering from painful osseous metastases and treated with (186)Re-HEDP. None had received any treatment that would have interfered with bone metabolism before (186)Re-HEDP treatment or throughout the follow-up period. For each patient, pretreatment and posttreatment serum levels of osteocalcin (OC), bone alkaline phosphatase (BALP), aminoterminal (PINP) and carboxyterminal (PICP) propeptides of type I collagen, amino-terminal (NTx) and carboxyterminal (CTx) telopeptides of type I collagen and their combinations were compared with the level and duration of pain response to radionuclide treatment. RESULTS: Pain response was correlated only with pretreatment NuTaux/PINP, PICP/PINP and NTx/CTx ratios and posttreatment decrease in baseline NTx and PICP values (p = 0.0025-0.035). According to multivariate and ROC analyses, the best marker-derived predictors of better and longer duration of response to (186)Re-HEDP treatment were a posttreatment decrease in NTx of > or = 20% (RR = 3.44, p = 0.0005) and a pretreatment NTx/PINP ratio of > or = 1.2 (RR = 3.04, p = 0.036) CONCLUSION: NTx, a potent collagenous marker of bone resorption, along with the novel NTx/PINP ratio provide useful cut-off values for identifying a group of patients suffering from painful osseous metastases from hormone-refractory prostatic carcinoma who do not respond to palliative treatment with (186)Re-HEDP. This information could help avoid an inefficient and expensive radionuclide treatment. Also, in the cohort of patients who will eventually undergo such treatment, the medium-term posttreatment changes in NTx offer valuable predictive information regarding long-term palliative response.

Clinical and imaging correlations of bone turnover markers in prostate cancer patients with bone only metastases.

OBJECTIVES: To correlate serum levels of bone markers with pain levels and extent of skeletal disease (EOD), in patients suffering from prostate cancer with bone only metastases. METHODS: Thirty-six males with hormone-refractory prostate carcinoma, bone only metastases and no history of therapies, drugs, or diseases that affect bone metabolism were studied. Karnofsky performance status, pain scoring, EOD, osteocalcin (OC), prostate-specific antigen, bone alkaline phosphatase amino-terminal and carboxy-terminal propeptides and telopeptides of type I collagen were analysed. Twenty-four healthy controls of the same age were also established. RESULTS: With only the exception of OC, bone marker values of patients were significantly increased compared with the upper reference limits (P<0.0001 for bone alkaline phosphatase and amino-terminal telopeptide of type I collagen, 0.012 for amino-terminal propeptide of type I collagen, 0.0023 for carboxy-terminal propeptide of type I collagen, and 0.04 for carboxy-terminal telopeptide of type I collagen). All bone markers and prostate-specific antigen also showed significant paired correlations (P < or = 0.019) and linear increases with advancing EOD (P < or = 0.032). Finally, none of the measured markers correlated significantly with pain levels. CONCLUSION: Bone markers are remarkably elevated in the serum of prostate cancer patients with metastatic bone disease and correlate with EOD. Paired correlations also suggest an accelerated but proportional (coupled) bone metabolism.

Management of metastatic bone pain with repeated doses of rhenium 186-HEDP in patients under therapy with zoledronic acid: a safe and additively effective practice.

PURPOSE: The aim of this study was to compare pain response and hematologic toxicity between single and multiple therapies with (186)Re-HEDP under zoledronic acid in patients suffering from painful osseous metastases from prostate or breast cancer. MATERIALS AND METHODS: Forty-five (45) patients received multiple therapies of (186)Re-HEDP (n = 77), under a stable regimen of analgesics and zoledronic acid, far off other therapeutic manipulations, and with no extraosseous disease progression. Hematologic status and pain indices were followed up regularly. RESULTS: Evaluable patients (n = 12), received 31 (186)Re-HEDP therapies. After the first treatment with (186)Re-HEDP, the mean percentile decrease for hemoglobin was 4.7%, for white blood cells was 21.4%, and for platelets was 12%. After multiple therapies, the respective declines were 7.0%, 16.0%, and 23.4%. With respect to baseline blood counts, only thrombocytes showed a tendency for greater decrease after repeated treatments, yet not of clinical significance. Favorable clinical response occurred after the first therapy in 10 of 12 patients (83.3%), after multiple doses in 15 of 19 (78.9%), and overall in 25 of 31 (80.6%) of (186)Re-HEDP therapies. Significant post-therapy improvement in pain indices was observed in all cases, regardless of the number of therapeutic doses. CONCLUSIONS: Retreatments with (186)Re-HEDP under zoledronic acid provide continuing effectiveness in metastatic bone pain and are safe enough, if an acceptable baseline hematologic status exists.

Can response to palliative treatment with radiopharmaceuticals be further enhanced?

Bone-seeking radiopharmaceuticals (RF) are an effective systemic pain-palliative treatment schedule in patients with disseminated bone disease. This treatment relies on selective uptake and prolonged retention of RF at sites of increased osteoblastic activity, while the potential toxicity of systemic administration is reduced by relatively selective tumour targeting. The main theoretic advantage of bone-targeted radionuclide treatment is that radiation can be delivered selectively to subclinical tumours and to metastases that are too small to be imaged and treated by surgical excision or local external beam radiotherapy. The distribution of radiation dose throughout a tumour is heterogeneous, whilst the rate of response depends upon the pre-treatment condition of the patient and other factors. To enhance the effect of treatment with RF on cancer cells, the following strategies have been investigated: Individualisation of the administered dose, higher-doses, earlier or repeated radionuclide treatment, the use of new RF, and the use of a mixture of different RF. Furthermore, external beam radiotherapy, biphosphonates or chemotherapeutic agents have been combined with RF and have scored significantly better treatment results referring to pain relief, bone disease progression, etc, without important side effects. The role of bone seeking RF can be extended beyond bone pain palliation, to a synergistic anti-tumour effect.