technetium-tc-99m-medronate and Prostatic-Neoplasms--Castration-Resistant

Understanding the mechanisms driving disease progression is fundamental to identifying new therapeutic targets for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC). Owing to the prevalence of bone metastases in mCRPC, obtaining sufficient tumor tissue for analysis has historically been a challenge. In this exploratory analysis, we evaluated imaging, procedural and clinical variables associated with tumor yield on image-guided bone biopsy in men with mCRPC.. Clinical data were collected prospectively from men with mCRPC enrolled on a phase II trial with serial metastasis biopsies performed according to standard clinical protocol. Imaging was retrospectively reviewed. We evaluated the percent positive biopsy cores (PPC), calculated as the number of positive cores divided by the total number of cores collected per biopsy.. Twenty-nine men had 39 bone biopsies. Seventy-seven percent of bone biopsies had at least one positive biopsy core. We determined that lesion size and distance from the skin to the lesion edge correlated with tumor yield on biopsy (median PPC 75% versus 42% for lesions >8.8 cm(3) versus ⩽ 8.8 cm(3), respectively, P=0.05; median PPC 33% versus 71% for distance ⩾ 6.1 versus <6.1 cm, respectively, P = 0.02). There was a trend towards increased tumor yield in patients with increased uptake on radionuclide bone scan, higher calcium levels and shorter duration of osteoclast-targeting therapy, although this was not statistically significant. Ten men had 14 soft tissue biopsies. All soft tissue biopsies had at least one positive biopsy core.. This exploratory analysis suggests that there are imaging, procedural and clinical variables that have an impact on image-guided bone biopsy yield. In order to maximize harvest of prostate cancer tissue, we have incorporated a prospective analysis of the metrics described here as part of a multi-institutional project aiming to use the molecular characterization of mCRPC tumors to direct individual therapy.

Topics: Aged; Androgen Antagonists; Androstenes; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Azasteroids; Biopsy; Bone Neoplasms; Drug Resistance, Neoplasm; Dutasteride; Humans; Male; Middle Aged; Prostatic Neoplasms, Castration-Resistant; Radiography, Interventional; Radionuclide Imaging; Radiopharmaceuticals; Surgery, Computer-Assisted; Technetium Tc 99m Medronate

Based on the SUV measurements of non-pathological bones, the optimal SUV threshold, which defines abnormal bone SPECT uptake, was determined to be 8. Median LUV was 39 mL (interquartile range 4.0-104.3 mL) in the CRPC subjects with bone metastases. Kaplan-Meier survival analysis showed a significant relation between prostate cancer-specific survival and LUV (cut-off value, 19.95 mL; P = 0.001). Multivariate analysis revealed LUV as an independent prognostic factor for the survival (P = 0.008, hazard ratio 23.424). Global chi-square test showed that LUV had significant incremental prognostic value in addition to prostate-specific antigen and the interval from progression to CRPC until bone SPECT/CT (P = 0.022).. Quantitative assessment of

Topics: Bone Neoplasms; Castration; Humans; Male; Prognosis; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Single Photon Emission Computed Tomography Computed Tomography; Technetium Tc 99m Medronate; Tomography, Emission-Computed, Single-Photon

A 75-year-old man with castrate-resistant prostate cancer and increasing prostate-specific antigen (PSA) level developed severe bone marrow depression during Ra radionuclide therapy. Because of this, he was treated with Lu-PSMA in compassionate use for this not-yet-approved therapy. At the beginning of Lu-PSMA therapy, repeated blood transfusions (BT) were necessary. Six months after the last BT, after 3 cycles of Lu-PSMA, his blood count stabilized. He required no further BTs and his PSA level remained lowered.

Topics: Aged; Anemia; Antineoplastic Agents; Bone Marrow Diseases; Bone Neoplasms; Compassionate Use Trials; Dipeptides; Edetic Acid; Gallium Isotopes; Gallium Radioisotopes; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Oligopeptides; Positron Emission Tomography Computed Tomography; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Radionuclide Imaging; Radiopharmaceuticals; Radium; Technetium Tc 99m Medronate

Prostate cancer is incurable once it has metastasized to the bone. Appropriate preclinical models are lacking. The therapeutic efficacy of the multikinase inhibitor cabozantinib was assessed in an orthotopic xenograft model of castration-resistant prostate cancer (CRPC) bone metastasis using noninvasive, multimodality functional imaging.. NOD/SCID mice were injected intratibially with luciferase-expressing ERG (v-ets avian erythroblastosis virus E26 oncogene homolog) rearranged VCaP human prostate carcinoma cells. The response of VCaP xenografts (n = 7 per group) to cabozantinib was investigated using bioluminescence imaging and anatomical and diffusion weighted magnetic resonance imaging. This enabled quantitation of tumor volume and apparent diffusion coefficient (ADC). Bone uptake of technetium-methylene diphosphonate ((99m)Tc-MDP) was assessed by single-photon emission computed tomography. Ex vivo micro computed tomography was used to quantify bone volume and correlated with appropriate histopathology. Statistical significance was determined using the two-sided Mann-Whitney test or Wilcoxon signed rank test.. VCaP xenografts were predominantly osteosclerotic with some osteolytic activity. Fluorescent in situ hybridization analysis confirmed retention of ERG oncogene rearrangements. Cabozantinib induced a statistically significant 52% reduction in tumor luminance (P = .02) and stasis in tumor volume after 15 days of treatment. Tumor ADC statistically significantly increased with cabozantinib and was associated with extensive necrosis (after 10 days, mean tumor ADC ± SD = 556±43×10(-6) mm(2)/s vs pretreatment ADC = 485±43×10(-6) mm(2)/s; P = .02 ). Tumor-associated uptake of (99m)Tc-MDP was statistically significantly reduced after 3 days of treatment (P = .02), sustained over 15 days treatment, and associated with a statistically significant (P = .048) reduction in bone growth on the tibial cortex, yet a highly statistically significant (P = .001) increase in trabecular bone volume.. The intratibial VCaP model faithfully emulates clinical disease. Cabozantinib exerts potent effects on both tumor and tumor-induced bone matrix remodeling, and quantitation of ADC provides a clinically translatable imaging biomarker for early, sensitive assessment of treatment response in CRPC bone metastasis.

Topics: Aged; Anilides; Animals; Antineoplastic Agents; Biomarkers, Tumor; Bone Neoplasms; Bone Remodeling; Diffusion Magnetic Resonance Imaging; Humans; Luminescent Measurements; Male; Mice; Mice, Inbred NOD; Mice, Nude; Middle Aged; Osteolysis; Osteosclerosis; Prostatic Neoplasms, Castration-Resistant; Pyridines; Radiopharmaceuticals; Receptor Protein-Tyrosine Kinases; Technetium Tc 99m Medronate; Tomography, Emission-Computed, Single-Photon; Tumor Burden; Xenograft Model Antitumor Assays