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Supplementary materials for Fendler et al.

Purpose:Systemic androgen-signaling inhibition added to ongoing androgen-deprivation therapy (ADT) improved clinical outcomes in patients with nonmetastatic castration-resistant prostate cancer without detectable metastases by conventional imaging (nmCRPC). Prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET) detects prostate cancer with superior sensitivity to conventional imaging, but its performance in nmCRPC remains largely unknown. We characterized cancer burden in high-risk patients with nmCRPC using PSMA-PET.Experimental Design:We retrospectively included 200 patients with nmCRPC, prostate-specific antigen (PSA) >2 ng/mL, and high risk for metastatic disease [PSA doubling time (PSADT) of ≤10 months and/or Gleason score of ≥8] from six high-volume PET centers. We centrally reviewed PSMA-PET detection rate for pelvic disease and distant metastases (M1). We further evaluated SPARTAN patients stratified by risk factors for PSMA-PET-detected M1 disease.Results:PSMA-PET was positive in 196 of 200 patients. Overall, 44% had pelvic diseases, including 24% with local prostate bed recurrence, and 55% had M1 disease despite negative conventional imaging. Interobserver agreement was very high (κ: 0.81–0.91). PSA ≥ 5.5 ng/mL, locoregional nodal involvement determined by pathology (pN1), prior primary radiation, and prior salvage radiotherapy independently predicted M1 disease (all P < 0.05).Conclusions:PSMA-PET detected any disease in nearly all patients and M1 disease in 55% of patients previously diagnosed with nmCRPC, including subgroups with PSADT of ≤10 months and Gleason score of ≥8. The value of PSMA-PET imaging for treatment guidance should be tested in future studies.

La tuberculosis (TB) es una de las enfermedades infecciosas con mayor carga de morbimortalidad a nivel mundial, la presentación pulmonar es la forma más común, sin embargo, las manifestaciones extrapulmonares, especialmente las osteoarticulares, pueden ser difíciles de diagnosticar debido a sus síntomas inespecíficos sugestivos de otras entidades como neoplasias o enfermedades infiltrativas, lo que hace de su diagnóstico un reto clínico. Está enfermedad esta asociada a múltiples factores de riesgo como inmunosupresión, contacto cercano con pacientes con tuberculosis, hacinamiento, residir en zona endémica, entre otros. A continuación, se presentan dos casos de pacientes pediátricos sin compromiso inmune que cursaron con cuadros sugestivos de neoplasias musculoesqueleticas, con hallazgos imagenológicos congruentes, pero con estudios microbiológicos positivos para TB.

Bone is the most common site of distant metastatic spread in prostate adenocarcinoma. Prostate-specific membrane antigen uptake has been described in both benign and malignant bone lesions, which can lead to false-positive findings on 68Ga-prostate-specific membrane antigen-11 positron emission tomography (68Ga-PSMA-11 PET). The purpose of this study was to evaluate the diagnostic accuracy of 68Ga-PSMA-11 PET for osseous prostate cancer metastases and improve bone uptake interpretation using semi-quantitative metrics. METHODS: 56 prostate cancer patients (18 pre-prostatectomy, 38 biochemical recurrence) who underwent 68Ga-PSMA-11 PET/MRI or PET/CT examinations with osseous PSMA-ligand uptake were included in the study. Medical records were reviewed retrospectively by board-certified nuclear radiologists to determine true or false positivity based on a composite endpoint. For each avid osseous lesion, biological volume, size, PSMA-RADS rating, maximum standardized uptake value (SUVmax), and ratio of lesion SUVmax to liver, blood pool, and background bone SUVmax were measured. Differences between benign and malignant lesions were evaluated for statistical significance, and cut-off values for these parameters were determined to maximize diagnostic accuracy. RESULTS: Among 56 participants, 13 patients (22.8%) had false-positive osseous 68Ga-PSMA-11 findings and 43 patients (76.8%) had true-positive osseous 68Ga-PSMA-11 findings. Twenty-two patients (39%) had 1 osseous lesion, 18 (32%) had 2-4 lesions, and 16 (29%) had 5 or more lesions. Cut-off values resulting in statistically significant (p

Alterations in Zn2+ concentration are seen in normal tissues and in disease states, and for this reason imaging of Zn2+ is an area of active investigation. Herein, enriched [1-13 C]cysteine and [1-13 C2 ]iminodiacetic acid were developed as Zn2+ -specific imaging probes using hyperpolarized 13 C magnetic resonance spectroscopy. [1-13 C]cysteine was used to accurately quantify Zn2+ in complex biological mixtures. These sensors can be employed to detect Zn2+ via imaging mechanisms including changes in 13 C chemical shift, resonance linewidth, or T1 .

We present a case of a 61-year-old man with history of prostate cancer and rising PSA levels referred for restaging. Ga-PSMA-11 PET/CT identified 2 lung nodules with low and moderate PSMA uptake. Subsequent F-FDG PET/CT showed high hypermetabolism in the nodule with low PSMA uptake, and low hypermetabolism in the nodule with moderate PSMA uptake. The isolated pulmonary findings and metabolic appearance is an atypical presentation of prostate cancer metastases and raised concern for a second primary malignancy. Fine-needle aspiration of the F-FDG active lung nodule confirmed metastatic prostatic adenocarcinoma that subsequently responded to androgen deprivation therapy and abiraterone acetate.

Background: Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome driven by ectopic production of fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting, hypophosphatemia, and bone demineralization. Successful therapy requires complete resection of the tumor, which is often challenging to localize. Clinical Case: A bedridden 37-year-old woman presented to Endocrine Clinic after 9 years of progressive pain and weakness in her back, hips, and extremities. She had previously been diagnosed with a neurodegenerative disease, though an MRI from 5 years ago showed bilateral subacute sacral ala fractures. CT scan on presentation showed generalized osteopenia and numerous subacute to chronic atraumatic fractures (involving ribs, scapula, pubic rami, and right femoral shaft) concerning for osteomalacia. On exam, she had profound lower extremity weakness. Laboratory testing was notable for serum phosphorus 0.6 mg/dL (normal (nl) 2.5-4.9), calcium 8.4 mg/dL (nl 8.5-10.5), PTH 216 pg/mL (nl 13-85), 25-OH vitamin D 26 ng/mL (nl 30-100), alkaline phosphatase 345 U/L (nl 45-130), 1,25-(OH)2 vitamin D 28 pg/mL (nl 18-72), renal tubular phosphorus reabsorption TmP/GFR 0.53 mg/dL (nl 2.97-4.45), and inappropriately normal FGF23 level 170 RU/mL (nl

Bone is the most common site of distant metastatic spread in prostate adenocarcinoma. Prostate-specific membrane antigen (PSMA) uptake has been described in both benign and malignant bone lesions, which can lead to false-positive findings on

Alterations in Zn(2+) concentration are seen in normal tissues and in disease states, and for this reason imaging of Zn(2+) is an area of active investigation. Herein, enriched [1-(13)C]cysteine and [1-(13)C(2)]iminodiacetic acid were developed as Zn(2+)-specific imaging probes using hyperpolarized (13)C magnetic resonance spectroscopy. [1-(13)C]cysteine was used to accurately quantify Zn(2+) in complex biological mixtures. These sensors can be employed to detect Zn(2+) via imaging mechanisms including changes in (13)C chemical shift, resonance linewidth, or T(1).

We present the case of an 87-year-old man with a history of melanoma metastatic to the lungs found to have an FDG-negative liver lesion that was initially thought to be benign. Follow-up CT revealed growth of the liver lesion despite excellent response to nivolumab therapy of the pulmonary melanoma metastases. Biopsy of the lesion confirmed primary hepatocellular carcinoma. Follow-up F-FDG PET/CT showed minimal FDG uptake, slightly above liver background, and subsequent Ga-PSMA-11 PET/MR showed focal, intense uptake of radiotracer in a different region of the tumor. These imaging findings support intratumor metabolic heterogeneity with radiotracer uptake in different tumor locations.

Purpose: Systemic androgen-signaling inhibition added to ongoing androgen-deprivation therapy (ADT) improved clinical outcomes in patients with nonmetastatic castration-resistant prostate cancer without detectable metastases by conventional imaging (nmCRPC). Prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET) detects prostate cancer with superior sensitivity to conventional imaging, but its performance in nmCRPC remains largely unknown. We characterized cancer burden in high-risk patients with nmCRPC using PSMA-PET. Experimental Design: We retrospectively included 200 patients with nmCRPC, prostate-specific antigen (PSA) >2 ng/mL, and high risk for metastatic disease [PSA doubling time (PSADT) of ≤10 months and/or Gleason score of ≥8] from six high-volume PET centers. We centrally reviewed PSMA-PET detection rate for pelvic disease and distant metastases (M1). We further evaluated SPARTAN patients stratified by risk factors for PSMA-PET-detected M1 disease. Results: PSMA-PET was positive in 196 of 200 patients. Overall, 44% had pelvic diseases, including 24% with local prostate bed recurrence, and 55% had M1 disease despite negative conventional imaging. Interobserver agreement was very high (κ: 0.81–0.91). PSA ≥ 5.5 ng/mL, locoregional nodal involvement determined by pathology (pN1), prior primary radiation, and prior salvage radiotherapy independently predicted M1 disease (all P < 0.05). Conclusions: PSMA-PET detected any disease in nearly all patients and M1 disease in 55% of patients previously diagnosed with nmCRPC, including subgroups with PSADT of ≤10 months and Gleason score of ≥8. The value of PSMA-PET imaging for treatment guidance should be tested in future studies.

Fusion proteins provide a facile route for the purification and self-assembly of biofunctional protein block copolymers into complex nanostructures; however, the use of biochemical synthesis techniques introduces unexplored variables into the design of the structures. Using model fusion constructs of the red fluorescent protein mCherry and the coil-like protein elastin-like polypeptide (ELP), it is shown that the molar mass and hydrophobicity of the ELP sequence have a large effect on the propensity of a fusion to form well-ordered nanostructures, even when the ELP is in the low temperature, highly solvated state. In contrast, the presence of a 6xHis purification tag has little effect on self-assembly, and the order of blocks in the construct (N-terminal vs C-terminal) only has a significant effect on the nanostructure when the conjugates are heated above the transition temperature of the ELP block. These results indicate that for a sufficiently hydrophobic and high molar mass ELP block, there is a great deal of design latitude in the construction of fusion protein block copolymers for self-assembling nanomaterials.

Poster: "EANM 19 / OP-105 / Prostate-Specific Membrane Antigen Positron-Emission Tomography (PSMA-PET) in High-Risk Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC) SPARTAN-like Patients Negative by Conventional Imaging" by: "W. Fendler1, M. M. Weber1, A. Iravani2, M. S. Hofman2, J. Calais3, J. Czernin3, H. Ilhan4, F. Saad5, E. J. Small6, M. R. Smith7, P. M. Perez6, T. Hope6, I. Rauscher8, A. Londhe9, A. Lopez-Gitlitz10, S. Cheng11, T. Maurer8, K. Herrmann1, B. Hadaschik12, M. Eiber8; 1Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK), partner site University Hospital Essen, Essen, GERMANY, 2Department of Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, AUSTRALIA, 3Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, UNITED STATES OF AMERICA, 4Department of Nuclear Medicine, Ludwig Maximilian University, Munich, GERMANY, 5Centre Hospitalier de l'Universite de Montreal, Universite de Montreal, Montreal, CANADA, 6Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, UNITED STATES OF AMERICA, 7Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, UNITED STATES OF AMERICA, 8Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, GERMANY, 9Janssen Research & Development, Titusville, UNITED STATES OF AMERICA, 10Janssen Research & Development, Los Angeles, UNITED STATES OF AMERICA, 11Janssen Research & Development, Raritan, UNITED STATES OF AMERICA, 12Department of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK), partner site University Hospital Essen, Essen, GERMANY"

With the rise of research utilizing microphysiological systems (MPSs), the need for tools that enable the physiological mimicking of the relevant cellular environment is vital. The limited ability to reproduce crucial features of the microenvironment, such as surrounding fluid flow and dynamic changes in biochemical stimuli, severely limits the types of experiments that can be carried out. Current equipment to achieve this, such as syringe and peristaltic pumps, is expensive, large, difficult to program and has limited potential for scalability. Here, we present a new pumping platform that is open-source, low-cost, modular, scalable, fully-programmable and easy to assemble that can be incorporated into cell culture systems to better recapitulate physiological environments. By controlling two commercially available piezoelectric pumps using a Raspberry Pi Zero microcontroller, the system is capable of producing arbitrary dynamic flow profiles with reliable flow rates ranging from 1 to 3000 µL/min as specified by an easily programmable Python-based script. We validated the accuracy of the flow rates, the use of time-varying profiles, and the practicality of the system by creating repeatable dynamic concentration profiles using a 3D-printed static micromixer., United States. Defense Advanced Research Projects Agency. Microphysiological Systems Program (W911NF-12-2-0039)