63 research outputs found
Interobserver agreement rates on C-X-C Motif chemokine receptor 4âdirected molecular imaging and therapy
Impact of tumor burden on normal organ distribution in patients imaged with CXCR4-targeted [68Ga]Ga-PentixaFor PET/CT
BACKGROUND: CXCR4-directed positron emission tomography/computed tomography (PET/CT) has been used as a diagnostic tool in patients with solid tumors. We aimed to determine a potential correlation between tumor burden and radiotracer accumulation in normal organs. METHODS: Ninety patients with histologically proven solid cancers underwent CXCR4-targeted [(68)Ga]Ga-PentixaFor PET/CT. Volumes of interest (VOIs) were placed in normal organs (heart, liver, spleen, bone marrow, and kidneys) and tumor lesions. Mean standardized uptake values (SUV(mean)) for normal organs were determined. For CXCR4-positive tumor burden, maximum SUV (SUV(max)), tumor volume (TV), and fractional tumor activity (FTA, defined as SUV(mean) x TV), were calculated. We used a Spearman's rank correlation coefficient (Ï) to derive correlative indices between normal organ uptake and tumor burden. RESULTS: Median SUV(mean) in unaffected organs was 5.2 for the spleen (range, 2.44 â 10.55), 3.27 for the kidneys (range, 1.52 â 17.4), followed by bone marrow (1.76, range, 0.84 â 3.98), heart (1.66, range, 0.88 â 2.89), and liver (1.28, range, 0.73 â 2.45). No significant correlation between SUV(max) in tumor lesions (Ïââ€â0.189, Pââ„â0.07), TV (Ïââ„â-0.204, Pââ„â0.06) or FTA (Ïââ„â-0.142, Pââ„â0.18) with the investigated organs was found. CONCLUSIONS: In patients with solid tumors imaged with [(68)Ga]Ga-PentixaFor PET/CT, no relevant tumor sink effect was noted. This observation may be of relevance for therapies with radioactive and non-radioactive CXCR4-directed drugs, as with increasing tumor burden, the dose to normal organs may remain unchanged
High SUVs have more robust repeatability in patients with metastatic prostate cancer: results from a prospective test-retest cohort imaged with 18F-DCFPyL
OBJECTIVES: In patients with prostate cancer (PC) receiving prostate-specific membrane antigen- (PSMA-) targeted radioligand therapy (RLT), higher baseline standardized uptake values (SUVs) are linked to improved outcome. Thus, readers deciding on RLT must have certainty on the repeatability of PSMA uptake metrics. As such, we aimed to evaluate the test-retest repeatability of lesion uptake in a large cohort of patients imaged with (18)F-DCFPyL. METHODS: In this prospective, IRB-approved trial (NCT03793543), 21 patients with history of histologically proven PC underwent two (18)F-DCFPyL PET/CTs within 7 days (mean 3.7, range 1 to 7 days). Lesions in the bone, lymph nodes (LN), and other organs were manually segmented on both scans, and uptake parameters were assessed (maximum (SUV(max)) and mean (SUV(mean)) SUVs), PSMA-tumor volume (PSMA-TV), and total lesion PSMA (TL-PSMA, defined as PSMA â TV Ă SUV(mean))). Repeatability was determined using Pearson's correlations, within-subject coefficient of variation (wCOV), and Bland-Altman analysis. RESULTS: In total, 230 pairs of lesions (177 bone, 38 LN, and 15 other) were delineated, demonstrating a wide range of SUV(max) (1.5â80.5) and SUV(mean) (1.4â24.8). Including all sites of suspected disease, SUVs had a strong interscan correlation (R(2) â„ 0.99), with high repeatability for SUV(mean) and SUV(max) (wCOV, 7.3% and 12.1%, respectively). High SUVs showed significantly improved wCOV relative to lower SUVs (P < 0.0001), indicating that high SUVs are more repeatable, relative to the magnitude of the underlying SUV. Repeatability for PSMA-TV and TL-PSMA, however, was low (wCOV â„ 23.5%). Across all metrics for LN and bone lesions, interscan correlation was again strong (R(2) â„ 0.98). Moreover, LN-based SUV(mean) also achieved the best wCOV (3.8%), which was significantly reduced when compared to osseous lesions (7.8%, P < 0.0001). This was also noted for SUV(max) (wCOV, LN 8.8% vs. bone 12.0%, P < 0.03). On a compartment-based level, wCOVs for volumetric features were â„22.8%, demonstrating no significant differences between LN and bone lesions (PSMA-TV, Pâ=0.63; TL-PSMA, Pâ=0.9). Findings on an entire tumor burden level were also corroborated in a hottest lesion analysis investigating the SUV(max) of the most intense lesion per patient (R(2), 0.99; wCOV, 11.2%). CONCLUSION: In this prospective test-retest setting, SUV parameters demonstrated high repeatability, in particular in LNs, while volumetric parameters demonstrated low repeatability. Further, the large number of lesions and wide distribution of SUVs included in this analysis allowed for the demonstration of a dependence of repeatability on SUV, with higher SUVs having more robust repeatability
Optical control of L-Type Ca2+ channels using a diltiazem photoswitch
L-type Ca2+ channels (LTCCs) play a crucial role in excitation-contraction coupling and release of hormones from secretory cells. They are targets of antihypertensive and antiarrhythmic drugs such as diltiazem. Here, we present a photoswitchable diltiazem, FHU-779, which can be used to reversibly block endogenous LTCCs by light. FHU-779 is as potent as diltiazem and can be used to place pancreatic ÎČ-cell function and cardiac activity under optical control
Flow-based SPPS for protein synthesis: A perspective
Flowâbased approaches to solid phase peptide synthesis (SPPS) have been pursued since the method's early days, with anticipated gains in speed, reaction monitoring, and ease of automation. Here, we discuss how these advantages are being realized by synthesis at elevated temperature, facilitated by a 'preheat/activation' loop. This important modification both accelerates peptide synthesisâproviding a wealth of new data from inâline monitoringâand in conjunction with an optimized protocol, extends the length of peptides routinely accessible by stepwise synthesis. Streamlined synthesis of longer peptides will address a major challenge in chemical protein synthesis: preparation of peptide segments for use in chemical ligation. The context of recent results in flowâbased SPPS is discussed, highlighting remaining challenges and future opportunities
Projektvorstellung: Multimorbide Menschen in der ambulanten Betreuung: Patientenzentriertes, Bedarfsorientiertes Versorgungsmanagement (MamBo)
Lebensbedrohliche Meningeome bei Neurofibromatose Typ II - eine Indikation fĂŒr eine Peptid-Rezeptor-Radionuklid-Therapie?
An expanded palette of photoswitchable sphingolipids for optical control of lipid microdomains
CXCR4-directed PET/CT in patients with newly diagnosed neuroendocrine carcinomas
We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUVmean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard F-FDG PET/CT
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