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Utilizing 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT), we performed this pilot study to evaluate the link between cytogenetic/genomic markers and imaging patterns in relapsed/refractory (RR) multiple myeloma (MM). We retrospectively analyzed data of 24 patients with RRMM who were treated at our institution between November 2018 and February 2020. At the last relapse/progression, patients had been treated with a median of three (range 1–10) lines of therapy. Six (25%) patients showed FDG avid extramedullary disease without adjacency to bone. We observed significantly higher maximum standardized uptake values (SUV\(_{max}\)) in patients harboring del(17p) compared with those without del(17p) (p = 0.025). Moreover, a high SUV\(_{max}\) of >15 indicated significantly shortened progression-free survival (PFS) (p = 0.01) and overall survival (OS) (p = 0.0002). One female patient exhibited biallelic TP53 alteration, i.e., deletion and mutation, in whom an extremely high SUV\(_{max}\) of 37.88 was observed. In summary, this pilot study suggested a link between del(17p)/TP53 alteration and high SUV\(_{max}\) on 18F-FDG PET/CT in RRMM patients. Further investigations are highly warranted at this point.
This study aimed to explore the correlation between imaging patterns and clinical features in patients with smoldering multiple myeloma (SMM) who simultaneously underwent 18F-FDG, 11C-Methionine, and 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT). We retrieved and analyzed clinical characteristics and PET imaging data of 10 patients with SMM. We found a significant correlation between bone marrow (BM) plasma cell (PC) infiltration and mean standardized uptake values (SUV\(_{mean}\)) of lumbar vertebrae L2-L4 on 11C-Methionine PET/CT scans (r = 0.676, p = 0.031) and 68Ga-Pentixafor PET/CT scans (r = 0.839, p = 0.002). However, there was no significant correlation between BM involvement and SUV\(_{mean}\) of lumbar vertebrae L2-L4 on 18F-FDG PET/CT scans (r = 0.558, p = 0.093). Similarly, mean target-to-background ratios (TBR\(_{mean}\)) of lumbar vertebrae L2-L4 also correlated with bone marrow plasma cell (BMPC) infiltration in 11C-Methionine PET/CT (r = 0.789, p = 0.007) and 68Ga-Pentixafor PET/CT (r = 0.724, p = 0.018) PET/CT. In contrast, we did not observe a significant correlation between BMPC infiltration rate and TBR\(_{mean}\) in 18F-FDG PET/CT (r = 0.355, p = 0.313). Additionally, on 11C-Methionine PET/CT scans, we found a significant correlation between BMPC infiltration and TBR\(_{max}\) of lumbar vertebrae L2-L4 (r = 0.642, p = 0.045). In conclusion, 11C-Methionine and 68Ga-Pentixafor PET/CT demonstrate higher sensitivity than 18F-FDG PET/CT in detecting BM involvement in SMM.
Purpose: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has become commonly utilized in patients with prostate cancer (PCa). The PSMA reporting and data system version 1.0 (PSMA-RADS version 1.0) categorizes lesions on the basis of the likelihood of PCa involvement, with PSMA-RADS-3A (soft tissue) and PSMA-RADS-3B (bone) lesions being indeterminate for the presence of disease. We retrospectively reviewed the imaging follow-up of such lesions to determine the rate at which they underwent changes suggestive of underlying PCa.
Methods: PET/CT imaging with \(^{18}\)F-DCFPyL was carried out in 110 patients with PCa and lesions were categorized according to PSMA-RADS Version 1.0. 56/110 (50.9%) patients were determined to have indeterminate PSMA-RADS-3A or PSMA-RADS-3B lesions and 22/56 (39.3%) patients had adequate follow-up to be included in the analysis. The maximum standardized uptake values (SUV\(_{max}\)) of the lesions were obtained and the ratios of SUV\(_{max}\) of the lesions to SUV\(_{mean}\) of blood pool (SUV\(_{max}\)-lesion/SUV\(_{mean}\)-bloodpool) were calculated. Pre-determined criteria were used to evaluate the PSMA-RADS-3A and PSMA-RADS-3B lesions on follow-up imaging to determine if they demonstrated evidence of underlying malignancy.
Results: A total of 46 lesions in 22 patients were considered indeterminate for PCa (i.e. PSMA-RADS-3A (32 lesions) or PSMA-RADS-3B (14 lesions)) and were evaluable on follow-up imaging. 27/46 (58.7%) lesions demonstrated changes on follow-up imaging consistent with the presence of underlying PCa at baseline. These lesions included 24/32 (75.0%) PSMA-RADS-3A lesions and 3/14 (21.4%) lesions categorized as PSMA-RADS-3B. The ranges of SUVmax and SUVmax-lesion/SUVmean-bloodpool overlapped between those lesions demonstrating changes consistent with malignancy on follow-up imaging and those lesions that remained unchanged on follow-up.
Conclusion: PSMA-RADS-3A and PSMA-RADS-3B lesions are truly indeterminate in that proportions of findings in both categories demonstrate evidence of malignancy on follow-up imaging. Overall, PSMA-RADS-3A lesions are more likely than PSMA-RADS-3B lesions to represent sites of PCa and this information should be taken into when guiding patient therapy.
In der vorliegenden Studie wurde der mögliche Einfluß von heterophilen Antikörpern auf die Thyreoglobulinbestimmung in der Nachsorge beim Patienten mit differenziertem Schilddrüsenkarzinom untersucht. Dazu wurde bei 201 Patientenseren der Thyreoglobulinwert auf herkömmliche Weise und in einer Parallelbestimmung nach Vorbehandlung mit heterophilen Antikörper blocking tubes bestimmt. Dieses Vorgehen ermöglichte es, einen direkten Vergleich beider Messergebnisse anzustellen und einen möglichen Einfluß heterophiler Antikörper aufzudecken. Darüber hinaus wurde das selbe Verfahren bei einer heterogenen Kontrollgruppe angewandt. In 99% der Proben ergab sich kein signifikanter Unterschied zwischen den beiden Messergebnissen. Somit ist ein Einfluß von heterophilen Antikörpern auf die Thyreoglobulinbestimmung bei Patienten mit differenziertem Schilddrüsenkarzinom unwahrscheinlich.
BACKGROUND:
We observed a disproportional 18 F-fluorothymidine (F-FLT) uptake in follicular lymphoma (FL) relative to its low cell proliferation. We tested the hypothesis that the 'excess' uptake of 18 F-FLT in FL is related to error-prone DNA repair and investigated whether this also contributes to 18 F-FLT uptake in diffuse large B cell lymphoma (DLBCL).
METHODS:
We performed immunohistochemical stainings to assess the pure DNA replication marker MIB-1 as well as markers of both DNA replication and repair like PCNA, TK-1 and RPA1 on lymph node biopsies of 27 FLs and 35 DLBCLs. In 7 FL and 15 DLBCL patients, 18 F-FLT-PET had been performed.
RESULTS:
18 F-FLT uptake was lower in FL than in DLBCL (median SUVmax 5.7 vs. 8.9, p = 0,004), but the ratio of 18 F-FLT-SUVmax to percentage of MIB-1 positive cells was significantly higher in FL compared with DLBCL (p = 0.001). The median percentage of MIB-1 positive cells was 10% (range, 10% to 20%) in FL and 70% (40% to 80%) in DLBCL. In contrast, the median percentages of PCNA, TK-1 and RPA1 positive cells were 90% (range, 80 to 100), 90% (80 to 100) and 100% (80 to 100) in FL versus 90% (60 to 100), 90% (60 to 100) and 100% (80 to 100) in DLBCL, respectively.
CONCLUSIONS:
This is the first demonstration of a striking discordance between 18 F-FLT uptake in FL and tumour cell proliferation. High expression of DNA replication and repair markers compared with the pure proliferation marker MIB-1 in FL suggests that this discordance might be due to error-prone DNA repair. While DNA repair-related 18 F-FLT uptake considerably contributes to 18 F-FLT uptake in FL, its contribution to 18 F-FLT uptake in highly proliferative DLBCL is small. This apparently high contribution of DNA repair to the 18 F-FLT signal in FL may hamper studies where 18 F-FLT is used to assess response to cytostatic therapy or to distinguish between FL and transformed lymphoma.
Ziel: Der Therapieerfolg der Radiosynoviorthese sollte bei rheumatoider Arthritis und anderen entzündlichen Gelenkerkrankungen anhand subjektiver, objektiver, so wie laborchemischer und bildgebender Parameter prospektiv beurteilt werden. Methode: Es wurden insgesamt 174 Gelenke bei 97 Patienten behandelt, wobei 55% der Patienten an einer rheumatoiden Arthritis und 23% an einer aktivierten Arthrose litten.Die Veränderungen 6 Monate nach einer Radiosynoviorthese wurden sowohl an subjektiven, wie auch an objektiven Parametern (Schmerz, Schwellung, Gelenk-beweglichkeit) evaluiert. Zusätzlich wurden laborchemische Parameter (CRP, BSG), bildgebende Verfahren (Skelett-szintigraphie, MRT) und Einnahme von Medikamenten beurteilt. Eine weitere Befragung zum Wiederauftreten von Beschwerden (Rezidiv) erfolgte in Zeit-räumen zwischen einem und drei Jahren nach der Radiosynoviorthese. Ergebnisse: Gute Erfolge in 60 bis 80% der Fälle zeigten sich bei der klinischen Symptomatik, sowohl auf subjektiver, als auch auf objektiver Ebene, wobei sich in der Korrelationsanalyse niedrige Werte zwischen den subjektiven und objektiven Parametern ergeben hatten. Bei 55% der Gelenke hatte sich die Schmerzintensität verringert, 23% waren gänzlich schmerzfrei. Die objektiv gemessene Änderung der Gelenkbeweglichkeit hatte bei 73% eine Besserung ergeben, 12% waren uneingeschränkt beweglich, bei 68% war die Schwellung zurückgegangen. Die Radionuklidaufnahme in der Weichteilphase der Sklettszintigraphie verminderte sich bei 58% der Gelenke, die Kernspin-tomographie ergab bei 44% der Kniegelenke einen Entzündungsrückgang. Rezidive traten nach einem bis drei Jahren nur bei 15% der Patienten auf.Die labor-chemischen Parameter sowie die Medikamenteneinnahme wurden durch die Radiosynoviorthese nicht beeinflusst. Schlussfolgerung: Die Radiosynoviorthese liefert auf subjektiver und objektiver Ebene gute Ergebnisse im Sinne einer Besserung. Sie ist dabei eine schonende Therapieform, die ohne Risiken einer Operation gleichzeitig an mehreren Gelenke vorgenommen und gegebenfalls wiederholt werden kann. Sie bietet damit somit eine gute Therapie-möglichkeit im Rahmen der interdisziplinären Behandlungsformen dar.
Background
Reliable central venous access (CVC) is essential for hematology–oncology patients since frequent puncture of peripheral veins—e.g., for chemotherapy, antibiotic administration, repeated blood sampling, and monitoring—can cause unacceptable pain and psychological trauma, as well as severe side effects in cases of extravasation of chemotherapy drugs. However, CVC lines still carry major risk factors, including thrombosis, infection (e.g., entry site, tunnel, and luminal infections), and catheter dislocation, leakage, or breakage.
Methods
Here we performed a retrospective database analysis to determine the incidence of CVC-associated thrombosis in a single-center cohort of 448 pediatric oncologic patients, and to analyze whether any subgroup of patients was at increased risk and thus might benefit from prophylactic anticoagulation.
Results
Of the 448 patients, 269 consecutive patients received a CVC, and 55 of these 269 patients (20%) also had a thrombosis. Of these 55 patients, 43 had at least one CVC-associated thrombosis (total number of CVC-associated thrombosis: n = 52). Among all patients, the median duration of CVC exposure was 464 days. Regarding exposure time, no significant difference was found between patients with and without CVC-associated thrombosis. Subclavia catheters and advanced tumor stages seem to be the main risk factors for the development of CVC-associated thrombosis, whereas pharmacologic prophylaxis did not seem to have a relevant impact on the rate of thrombosis.
Conclusions
We conclude that pediatric surgeons and oncologists should pay close attention to ensuring optimal and accurate CVC placement, as this appears the most effective tool to minimize CVC-associated complications.
Inter-comparison of quantitative imaging of lutetium-177 (\(^{177}\)Lu) in European hospitals
(2018)
Background
This inter-comparison exercise was performed to demonstrate the variability of quantitative SPECT/CT imaging for lutetium-177 (\(^{177}\)Lu) in current clinical practice. Our aim was to assess the feasibility of using international inter-comparison exercises as a means to ensure consistency between clinical sites whilst enabling the sites to use their own choice of quantitative imaging protocols, specific to their systems.
Dual-compartment concentric spherical sources of accurately known activity concentrations were prepared and sent to seven European clinical sites. The site staff were not aware of the true volumes or activity within the sources—they performed SPECT/CT imaging of the source, positioned within a water-filled phantom, using their own choice of parameters and reported their estimate of the activities within the source.
Results
The volumes reported by the participants for the inner section of the source were all within 29% of the true value and within 60% of the true value for the outer section. The activities reported by the participants for the inner section of the source were all within 20% of the true value, whilst those reported for the outer section were up to 83% different to the true value.
Conclusions
A variety of calibration and segmentation methods were used by the participants for this exercise which demonstrated the variability of quantitative imaging across clinical sites. This paper presents a method to assess consistency between sites using different calibration and segmentation methods.
Disclosing the CXCR4 expression in lymphoproliferative diseases by targeted molecular imaging
(2015)
Chemokine ligand-receptor interactions play a pivotal role in cell attraction and cellular trafficking, both in normal tissue homeostasis and in disease. In cancer, chemokine receptor-4 (CXCR4) expression is an adverse prognostic factor. Early clinical studies suggest that targeting CXCR4 with suitable high-affinity antagonists might be a novel means for therapy. In addition to the preclinical evaluation of [\(^{68}\)Ga]Pentixafor in mice bearing human lymphoma xenografts as an exemplary CXCR4-expressing tumor entity, we report on the first clinical applications of [\(^{68}\)Ga]Pentixafor-Positron Emission Tomography as a powerful method for CXCR4 imaging in cancer patients. [\(^{68}\)Ga]Pentixafor binds with high affinity and selectivity to human CXCR4 and exhibits a favorable dosimetry. [\(^{68}\)Ga]Pentixafor-PET provides images with excellent specificity and contrast. This non-invasive imaging technology for quantitative assessment of CXCR4 expression allows to further elucidate the role of CXCR4/CXCL12 ligand interaction in the pathogenesis and treatment of cancer, cardiovascular diseases and autoimmune and inflammatory disorders.
Background: Precise regional quantitative assessment of renal function is limited with conventional \(^{99m}\)Tc-labeled renal radiotracers. A recent study reported that the positron emission tomography (PET) radiotracer 2-deoxy-2-(\(^{18}\)F-fluorosorbitol (\(^{18}\)F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, (\(^{18}\)F-FDS is available via simple reduction from routinely used 2-deoxy-2-(\(^{18}\)F-fluoro-D-glucose ((\(^{18}\)F-FDG). We aimed to further investigate the potential of (\(^{18}\)F-FDS PET as a functional renal imaging agent using rat models of kidney diseases.
Methods: Two different rat models of renal impairment were investigated: Glycerol induced acute renal failure (ARF) by intramuscular administration of glycerol in hind legs and unilateral ureteral obstruction (UUO) by ligation of the left ureter. 24h after these treatments, dynamic 30 min 18F-FDS PET data were acquired using a dedicated small animal PET system. Urine 18F-FDS radioactivity 30 min after radiotracer injection was measured together with co-injected \(^{99m}\)Tc-diethylenetriaminepentaacetic acid (\(^{99m}\)Tc-DTPA) urine activity. Results: Dynamic PET imaging demonstrated rapid (\(^{18}\)F-FDS accumulation in the renal cortex and rapid radiotracer excretion via kidneys in control healthy rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in ARF rats and UUO-treated kidneys. Measured urine radiotracer concentrations of (\(^{18}\)F-FDS and \(^{99m}\)Tc-DTPA were well correlated (R=0.84, P<0.05).
Conclusions: (\(^{18}\)F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. Advantages of high spatiotemporal resolution of PET imaging and simple tracer production could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging.