Refine
Has Fulltext
- yes (40)
Is part of the Bibliography
- yes (40)
Year of publication
Document Type
- Journal article (40) (remove)
Language
- English (40)
Keywords
- PET (11)
- theranostics (10)
- CXCR4 (8)
- Positronen-Emissions-Tomografie (7)
- neuroendocrine tumor (7)
- PET/CT (6)
- PRRT (6)
- multiple myeloma (6)
- molecular imaging (5)
- positron emission tomography (4)
Institute
- Klinik und Poliklinik für Nuklearmedizin (38)
- Medizinische Klinik und Poliklinik II (13)
- Institut für diagnostische und interventionelle Radiologie (Institut für Röntgendiagnostik) (6)
- Pathologisches Institut (6)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (4)
- Medizinische Klinik und Poliklinik I (4)
- Comprehensive Cancer Center Mainfranken (2)
- Institut für Klinische Biochemie und Pathobiochemie (2)
- Neurochirurgische Klinik und Poliklinik (2)
- Urologische Klinik und Poliklinik (2)
Sonstige beteiligte Institutionen
EU-Project number / Contract (GA) number
- 701983 (9)
Multiple myeloma (MM) remains an essentially incurable hematologic malignancy. However, new treatment modalities and novel drugs have been introduced and thus additional tools for therapy monitoring are increasingly needed. Therefore, we evaluated the radiotracers \(^{11}\)C-Methionine (paraprotein-biosynthesis) and \(^{18}\)F-FDG (glucose-utilization) for monitoring response to anti-myeloma-therapy and outcome prediction. Influence of proteasome-inhibition on radiotracer-uptake of different MM cell-lines and patient-derived CD138\(^{+}\) plasma cells was analyzed and related to tumor-biology. Mice xenotransplanted with MM. 1S tumors underwent MET- and FDG-\(\mu\)PET. Tumor-to-background ratios before and after 24 h, 8 and 15 days treatment with bortezomib were correlated to survival. Treatment reduced both MET and FDG uptake; changes in tracer-retention correlated with a switch from high to low CD138-expression. In xenotransplanted mice, MET-uptake significantly decreased by 30-79% as early as 24 h after bortezomib injection. No significant differences were detected thus early with FDG. This finding was confirmed in patient-derived MM cells. Importantly, early reduction of MET-but not FDG-uptake correlated with improved survival and reduced tumor burden in mice. Our results suggest that MET is superior to FDG in very early assessment of response to anti-myeloma-therapy. Early changes in MET-uptake have predictive potential regarding response and survival. MET-PET holds promise to individualize therapies in MM in future.
C-X-C motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. This study investigated the feasibility of CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using [\(^{68}\)Ga]Pentixafor in malignant pleural mesothelioma.
Six patients with pleural mesothelioma underwent [\(^{68}\)Ga]Pentixafor-PET/CT. 2′-[\(^{18}\)F]fluoro-2′-deoxy-D-glucose ([\(^{18}\)F]FDG)-PET/CT (4/6 patients) and immunohistochemistry obtained from biopsy or surgery (all) served as standards of reference. Additionally, 9 surgical mesothelioma samples were available for histological work-up.
Whereas [\(^{18}\)F]FDG-PET depicted active lesions in all patients, [\(^{68}\)Ga]Pentixafor-PET/CT recorded physiologic tracer distribution and none of the 6 patients presented [\(^{68}\)Ga]Pentixafor-positive lesions. This finding paralleled results of immunohistochemistry which also could not identify relevant CXCR4 surface expression in the samples analyzed.
In contrast to past reports, our data suggest widely absence of CXCR4 expression in pleural mesothelioma. Hence, robust cell surface expression should be confirmed prior to targeting this chemokine receptor for diagnosis and/or therapy.
C-X-C motif chemokine receptor 4 (CXCR4) and somatostatin receptors (SSTR) are overexpressed in gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). In this study, we aimed to elucidate the feasibility of non-invasive CXCR4 positron emission tomography/computed tomography (PET/CT) imaging in GEP-NET patients using [\(^{68}\)Ga]Pentixafor in comparison to \(^{68}\)Ga-DOTA-D-Phe-Tyr3-octreotide ([\(^{68}\)Ga]DOTATOC) and \(^{18}\)F-fluorodeoxyglucose ([\(^{18}\)F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [\(^{68}\)Ga]DOTATOC, [\(^{18}\)F]FDG, and [\(^{68}\)Ga]Pentixafor PET/CT for staging and planning of the therapeutic management. Scans were analyzed on a patient as well as on a lesion basis and compared to immunohistochemical staining patterns of CXCR4 and somatostatin receptors SSTR2a and SSTR5. [\(^{68}\)Ga]Pentixafor visualized tumor lesions in 6/12 subjects, whereas [\(^{18}\)F]FDG revealed sites of disease in 10/12 and [\(^{68}\)Ga]DOTATOC in 11/12 patients, respectively. Regarding sensitivity, SSTR-directed PET was the superior imaging modality in all G1 and G2 NET. CXCR4-directed PET was negative in all G1 NET. In contrast, 50% of G2 and 80% of G3 patients exhibited [\(^{68}\)Ga]Pentixafor-positive tumor lesions. Whereas CXCR4 seems to play only a limited role in detecting well-differentiated NET, increasing receptor expression could be non-invasively observed with increasing tumor grade. Thus, [\(^{68}\)Ga]Pentixafor PET/CT might serve as non-invasive read-out for evaluating the possibility of CXCR4-directed endoradiotherapy in advanced dedifferentiated SSTR-negative tumors.
Peptide Receptor Radionuclide Therapy (PRRT) for the treatment of neuroendocrine tumors may lead to kidney deterioration. This study aimed to evaluate the suitability of \(^{99m}\)Tc-mercaptoacetyltriglycine (\(^{99m}\)Tc-MAG3) clearance for the early detection of PRRT-induced changes on tubular extraction (TE). TE rate (TER) was measured prior to 128 PRRT cycles (7.6±0.4 GBq \(^{177}\)Lu-octreotate/octreotide each) in 32 patients. TER reduction during PRRT was corrected for age-related decrease and analyzed for the potential to predict loss of glomerular filtration (GF). The GF rate (GFR) as measure for renal function was derived from serum creatinine. The mean TER was 234 ± 53 ml/min/1.73 m² before PRRT (baseline) and 221 ± 45 ml/min/1.73 m² after a median follow-up of 370 days. The age-corrected decrease (mean: -3%, range: -27% to +19%) did not reach significance (p=0.09) but significantly correlated with the baseline TER (Spearman p=-0.62, p<0.001). Patients with low baseline TER showed an improved TER after PRRT, high decreases were only observed in individuals with high baseline TER. Pre-therapeutic TER data were inferior to plasma creatinine-derived GFR estimates in predicting late nephropathy. TER assessed by \(^{99m}\)Tc-MAG3clearance prior to and during PRRT is not suitable as early predictor of renal injury and an increased risk for late nephropathy.
Background
Peptide receptor radionuclide therapy (PRRT) is applied in patients with advanced neuroendocrine tumors. Co-infused amino acids (AA) should prevent nephrotoxicity. The aims of this study were to correlate the incidence of AA-induced hyperkalemia (HK) (≥5.0 mmol/l) and to identify predictors of AA-induced severe HK (>6.0).
Methods
In 38 patients, standard activity of \(^{177}Lu\)-labelled somatostatin analogs was administered. Pre-therapeutic kidney function was assessed by renal scintigraphy and laboratory tests. For kidney protection, AA was co-infused. Biochemical parameters (potassium, glomerular filtration rate, creatinine, blood urea nitrogen (BUN), sodium, phosphate, chloride, and lactate dehydrogenase (LDH)) were obtained prior to 4 and 24 h after the AA infusion. Incidence of HK (≥5.0) was correlated with pre-therapeutic kidney function and serum parameters. Formulas for the prediction of severe hyperkalemia (>6.0) were computed and prospectively validated.
Results
At 4 h, HK (≥5.0) was present in 94.7% with severe HK (>6.0) in 36.1%. Values normalized after 24 h in 84.2%. Pre-therapeutic kidney function did not correlate with the incidence of severe HK.
Increases in K+ were significantly correlated with decreases in phosphate (r = −0.444, p < 0.005) and increases in BUN (r = 0.313, p = 0.056). A baseline BUN of >28 mg/dl had a sensitivity of 84.6% and a specificity of 60.0% (AUC = 0.75) in predicting severe HK of >6.0 (phosphate, AUC = 0.37).
Computing of five standard serum parameters (potassium, BUN, sodium, phosphate, LDH) resulted in a sensitivity of 88.9% and a specificity of 79.3% for the prediction of severe HK >6.0 (accuracy = 81.6%).
Conclusions
A combination of serum parameters predicted prospectively the occurrence of relevant HK with an accuracy of 81.6% underlining its potential utility for identifying ‘high-risk’ patients prone to PRRT.
Background
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM) have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN′,N″,N′″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) labeled with Gallium-68 selectively binds to somatostatin receptor 2A (SSTR2A) which is specifically expressed and up-regulated in activated macrophages. On the other hand, the role of SSTR2A expression on the cell surface of glioma cells has not been fully elucidated yet. The aim of this study was to non-invasively assess SSTR2A expression of both glioma cells as well as macrophages in GBM.
Methods
15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68), proliferative activity (Ki67) as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET) imaging using \(^{68}Ga-DOTATATE\) was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry.
Results
The amount of microglia/macrophages ranged from <10% to >50% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns.
Conclusion
SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM.
The aim of this study was to investigate the prognostic value of 18F-fluoro-deoxyglucose positron emission tomography–computed tomography (18F-FDG-PET/CT) in 37 patients with a history of multiple myeloma (MM) and suspected or confirmed recurrence after stem cell transplantation (SCT). All patients had been heavily pre-treated. Time to progression (TTP) and overall survival (OS) were correlated to a number of different PET-derived as well as clinical parameters. Impact on patient management was assessed.
Absence of FDG-avid MM foci was a positive prognostic factor for both TTP and OS (p<0.01). Presence of >10 focal lesions correlated with both TTP (p<0.01) and OS (p<0.05). Interestingly, presence of >10 lesions in the appendicular skeleton proved to have the strongest association with disease progression. Intensity of glucose uptake and presence of extramedullary disease were associated with shorter TTP (p=0.037 and p=0.049, respectively). Manifestations in soft tissue structures turned out to be a strong negative predictor for both, TTP and OS (p<0.01, respectively). PET resulted in a change of management in 30% of patients.
Our data underline the prognostic value of 18F-FDG-PET/CT in MM patients also in the setting of post-SCT relapse. PET/CT has a significant impact on patient management.
Background
Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm with increasing incidence, aggressive behavior and poor prognosis. Somatostatin receptors (SSTR) are expressed in MCC and represent a potential target for both imaging and treatment.
Methods
To non-invasively assess SSTR expression in MCC using PET and the radiotracers [68Ga]DOTA-D-Phe1-Tyr3-octreotide (DOTATOC) or -octreotate (DOTATATE) as surrogate for tumor burden. In 24 patients with histologically proven MCC SSTR-PET was performed and compared to results of computed tomography (CT).
Results
SSTR-PET detected primary and metastatic MCC lesions. On a patient-based analysis, sensitivity of SSTR-PET was 73% for nodal metastases, 100% for bone, and 67% for soft-tissue metastases, respectively. Notably, brain metastases were initially detected by SSTR-PET in 2 patients, whereas liver and lung metastases were diagnosed exclusively by CT. SSTR-PET showed concordance to CT results in 20 out of 24 patients. Four patients (17%) were up-staged due to SSTR-PET and patient management was changed in 3 patients (13%).
Conclusion
SSTR-PET showed high sensitivity for imaging bone, soft tissue and brain metastases, and particularly in combination with CT had a significant impact on clinical stage and patient management.
Background
Peptide receptor radionuclide therapy (PRRT) is routinely used for advanced or metastasized neuroendocrine tumours (NET). To prevent nephrotoxicity, positively charged amino acids (AA) are co-infused. The aim of this study was to correlate the risk for therapy-related hyperkalaemia with the total amount of AA infused.
Methods
Twenty-two patients undergoing PRRT with standard activities of 177Lu-DOTATATE/-TOC were monitored during two following treatment cycles with co-infusion of 75 and 50 g of AA (L-arginine and L-lysine), respectively. Mean serum levels of potassium and other parameters (glomerular filtration rate [GFR], creatinine, blood urea nitrogen [BUN], phosphate, chloride, lactate dehydrogenase) prior to, 4 h and 24 h after AA infusion were compared.
Results
Self-limiting hyperkalaemia (>5.0 mmol/l) resolving after 24 h occurred in 91% (20/22) of patients in both protocols. Potassium levels, BUN, creatinine, GFR, phosphate, chloride and LDH showed a similar range at 4 h after co-infusion of 75 or 50 g of AA, respectively (p > 0.05). Only GFR and creatinine levels at 24 h varied significantly between the two co-infusion protocols (p < 0.05).
Conclusions
Hyperkalaemia is a frequent side effect of AA infusion in PRRT. Varying the dose of co-infused amino acids did not impact on the incidence and severity of hyperkalaemia.
We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer \(^{68}\)Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard \(^{18}\)F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent \(^{18}\)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. \(^{68}\)Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while \(^{18}\)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, \(^{18}\)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 \(^{68}\)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 \(^{18}\)F-FDG PET/CT.
Background: Ga-[1,4,7,10-tetraazacyclododecane-N,N0,N00,N000-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) positron emission tomography (PET) is commonly used for the visualization of somatostatin receptor (SSTR)-positive neuroendocrine tumors. SSTR is also known to be expressed on macrophages, which play a major role in inflammatory processes in the walls of coronary arteries and large vessels. Therefore, imaging SSTR expression has the potential to visualize vulnerable plaques. We assessed 68Ga-DOTATATE accumulation in large vessels in comparison to 18F-2-fluorodeoxyglucose (FDG) uptake, calcified plaques (CPs), and cardiovascular risk factors. Methods: Sixteen consecutive patients with neuroendocrine tumors or thyroid cancer underwent both 68Ga-DOTATATE and 18F-FDG PET/CT for staging or restaging purposes. Detailed clinical data, including common cardiovascular risk factors, were recorded. For a separate assessment, they were divided into a high-risk and a low-risk group. In each patient, we calculated the maximum target-to-background ratio (TBR) of eight arterial segments. The correlation of the TBRmean of both tracers with risk factors including plaque burden was assessed. Results: The mean TBR of 68Ga-DOTATATE in all large arteries correlated significantly with the presence of CPs (r = 0.52; p < 0.05), hypertension (r = 0.60; p < 0.05), age (r = 0.56; p < 0.05), and uptake of 18F-FDG (r = 0.64; p < 0.01). There was one significant correlation between 18F-FDG uptake and hypertension (0.58; p < 0.05). Out of the 37 sites with the highest focal 68Ga-DOTATATE uptake, 16 (43.2%) also had focal 18F-FDG uptake. Of 39 sites with the highest 18F-FDG uptake, only 11 (28.2%) had a colocalized 68Ga-DOTATATE accumulation. Conclusions: In this series of cancer patients, we found a stronger association of increased 68Ga-DOTATATE uptake with known risk factors of cardiovascular disease as compared to 18F-FDG, suggesting a potential role for plaque imaging in large arteries. Strikingly, we found that focal uptake of 68Ga-DOTATATE and 18F-FDG does not colocalize in a significant number of lesions.
(1) Background: We aimed to quantitatively investigate [\(^{68}\)Ga]Ga-FAPI-04 uptake in normal organs and to assess a relationship with the extent of FAPI-avid tumor burden. (2) Methods: In this single-center retrospective analysis, thirty-four patients with solid cancers underwent a total of 40 [\(^{68}\)Ga]Ga-FAPI-04 PET/CT scans. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were established by placing volumes of interest (VOIs) in the heart, liver, spleen, pancreas, kidneys, and bone marrow. Total tumor burden was determined by manual segmentation of tumor lesions with increased uptake. For tumor burden, quantitative assessment included maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA = TV × SUV\(_{mean}\)). Associations between uptake in normal organs and tumor burden were investigated by applying Spearman's rank correlation coefficient. (3) Results: Median SUV\(_{mean}\) values were 2.15 in the pancreas (range, 1.05–9.91), 1.42 in the right (range, 0.57–3.06) and 1.41 in the left kidney (range, 0.73–2.97), 1.2 in the heart (range, 0.46–2.59), 0.86 in the spleen (range, 0.55–1.58), 0.65 in the liver (range, 0.31–2.11), and 0.57 in the bone marrow (range, 0.26–0.94). We observed a trend towards significance for uptake in the myocardium and tumor-derived SUV\(_{max}\) (ρ = 0.29, p = 0.07) and TV (ρ = −0.30, p = 0.06). No significant correlation was achieved for any of the other organs: SUV\(_{max}\) (ρ ≤ 0.1, p ≥ 0.42), TV (ρ ≤ 0.11, p ≥ 0.43), and FTA (ρ ≤ 0.14, p ≥ 0.38). In a sub-analysis exclusively investigating patients with high tumor burden, significant correlations of myocardial uptake with tumor SUV\(_{max}\) (ρ = 0.44; p = 0.03) and tumor-derived FTA with liver uptake (ρ = 0.47; p = 0.02) were recorded. (4) Conclusions: In this proof-of-concept study, quantification of [\(^{68}\)Ga]Ga-FAPI-04 PET showed no significant correlation between normal organs and tumor burden, except for a trend in the myocardium. Those preliminary findings may trigger future studies to determine possible implications for treatment with radioactive FAP-targeted drugs, as higher tumor load or uptake may not lead to decreased doses in the majority of normal organs.
C-X-C-motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. We have recently reported promising first-in-man experience with CXCR4-directed endoradiotherapy (ERT) in multiple myeloma (MM).
Eight heavily pretreated MM patients underwent a total of 10 ERT cycles (7 patients with 1 cycle and a single patient with 3 cycles). ERT was administered in combination with chemotherapy and autologous stem cell support. End points were occurrence and timing of adverse events, progression-free and overall survival.
ERT was overall well tolerated without any unexpected acute adverse events or changes in vital signs. With absorbed tumor doses >30-70 Gy in intra- or extramedullary lesions, significant anti-myeloma activity was observed with 1 patient achieving complete remission and 5/8 partial remission. Directly after ERT major infectious complications were seen in one patient who died from sepsis 22 days after ERT, another patient with high tumor burden experienced lethal tumor lysis syndrome. Median progression-free survival was 54 days (range, 13-175), median overall survival was 223 days (range, 13-313). During follow-up (6 patients available), one patient died from infectious complications, 2/8 from disease progression, the remaining 3/8 patients are still alive.
CXCR4-directed ERT was well-tolerated and exerted anti-myeloma activity even at very advanced stage MM with presence of extramedullary disease. Further assessment of this novel treatment option is highly warranted.
Chemokine (C-X-C motif) receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer including multiple myeloma (MM). Proof-of-concept of CXCR4-directed radionuclide therapy in MM has recently been reported. This study assessed the diagnostic performance of the CXCR4-directed radiotracer [\(^{68}\)Ga]Pentixafor in MM and a potential role for stratifying patients to CXCR4-directed therapies.
Thirty-five patients with MM underwent [\(^{68}\)Ga]Pentixafor-PET/CT for evaluation of eligibility for endoradiotherapy. In 19/35 cases, [\(^{18}\)F]FDG-PET/CT for correlation was available. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with standard clinical parameters of disease activity.
[\(^{68}\)Ga]Pentixafor-PET detected CXCR4-positive disease in 23/35 subjects (66%). CXCR4-positivity at PET was independent from myeloma subtypes, cytogenetics or any serological parameters and turned out as a negative prognostic factor. In the 19 patients in whom a comparison to [\(^{18}\)F]FDG was available, [\(^{68}\)Ga]Pentixafor-PET detected more lesions in 4/19 (21%) subjects, [\(^{18}\)F]FDG proved superior in 7/19 (37%). In the remaining 8/19 (42%) patients, both tracers detected an equal number of lesions. [\(^{18}\)F]FDG-PET positivity correlated with [\(^{68}\)Ga]Pentixafor-PET positivity (p=0.018).
[\(^{68}\)Ga]Pentixafor-PET provides further evidence that CXCR4 expression frequently occurs in advanced multiple myeloma, representing a negative prognostic factor and a potential target for myeloma specific treatment. However, selecting patients for CXCR4 directed therapies and prognostic stratification seem to be more relevant clinical applications for this novel imaging modality, rather than diagnostic imaging of myeloma.
Objective: Radiotracers targeting prostate-specific membrane antigen (PSMA) have increasingly been recognized as showing uptake in a number of normal structures, anatomic variants, and non-prostate-cancer pathologies. We aimed to explore the frequency and degree of uptake in peripheral ganglia in patients undergoing PET with the PSMA-targeted agent \(^{18}\)F-DCFPyL.
Methods: A total of 98 patients who underwent \(^{18}\)F-DCFPyL PET/CT imaging were retrospectively analyzed. This included 76 men with prostate cancer (PCa) and 22 patients with renal cell carcinoma (RCC; 13 men, 9 women). Scans were evaluated for uptake in the cervical, stellate, celiac, lumbar and sacral ganglia. Maximum standardized uptake value corrected to body weight (SUV\(_{max}\)), and maximum standardized uptake value corrected to lean body mass (SUL\(_{max}\)) were recorded for all ganglia with visible uptake above background. Ganglia-to-background ratios were calculated by dividing the SUV\(_{max}\) and SUL\(_{max}\) values by the mean uptake in the ascending aorta (Aortamean) and the right gluteus muscle (Gluteusmean).
Results: Overall, 95 of 98 (96.9%) patients demonstrated uptake in at least one of the evaluated peripheral ganglia. With regard to the PCa cohort, the most frequent sites of radiotracer accumulation were lumbar ganglia (55/76, 72.4%), followed by the cervical ganglia (51/76, 67.1%). Bilateral uptake was found in the majority of cases [lumbar 44/55 (80%) and cervical 30/51 (58.8%)]. Additionally, discernible radiotracer uptake was recorded in 50/76 (65.8%) of the analyzed stellate ganglia and in 45/76 (59.2%) of the celiac ganglia, whereas only 5/76 (6.6%) of the sacral ganglia demonstrated \(^{18}\)F-DCFPyL accumulation. Similar findings were observed for patients with RCC, with the most frequent locations of radiotracer uptake in both the lumbar (20/22, 90.9%) and cervical ganglia (19/ 22, 86.4%). No laterality preference was found in mean PSMA-ligand uptake for either the PCa or RCC cohorts.
Conclusion: As PSMA-targeted agents become more widely disseminated, the patterns of uptake in structures that are not directly relevant to patients’ cancers must be understood. This is the first systematic evaluation of the uptake of \(^{18}\)F-DCFPyL in ganglia demonstrating a general trend with a descending frequency of radiotracer accumulation in lumbar, cervical, stellate, celiac, and sacral ganglia. The underlying biology that leads to variability of PSMA-targeted radiotracers in peripheral ganglia is not currently understood, but may provide opportunities for future research.
Objectives. This study is aimed at investigating the impact of frame numbers in preclinical electrocardiogram- (ECG-) gated \(^{18}\)F-fluorodeoxyglucose (\(^{18}\)F-FDG) positron emission tomography (PET) on systolic and diastolic left ventricular (LV) parameters in rats. Methods. \(^{18}\)F-FDG PET imaging using a dedicated small animal PET system with list mode data acquisition and continuous ECG recording was performed in diabetic and control rats. The list-mode data was sorted and reconstructed with different numbers of frames (4, 8, 12, and 16) per cardiac cycle into tomographic images. Using an automatic ventricular edge detection software, left ventricular (LV) functional parameters, including ejection fraction (EF), end-diastolic (EDV), and end-systolic volume (ESV), were calculated. Diastolic variables (time to peak filling (TPF), first third mean filling rate (1/3 FR), and peak filling rate (PFR)) were also assessed. Results. Significant differences in multiple parameters were observed among the reconstructions with different frames per cardiac cycle. EDV significantly increased by numbers of frames (353.8 & PLUSMN; 57.7 mu l*, 380.8 & PLUSMN; 57.2 mu l*, 398.0 & PLUSMN; 63.1 mu l*, and 444.8 & PLUSMN; 75.3 mu l at 4, 8, 12, and 16 frames, respectively; *P < 0.0001 vs. 16 frames), while systolic (EF) and diastolic (TPF, 1/3 FR and PFR) parameters were not significantly different between 12 and 16 frames. In addition, significant differences between diabetic and control animals in 1/3 FR and PFR in 16 frames per cardiac cycle were observed (P < 0.005), but not for 4, 8, and 12 frames. Conclusions. Using ECG-gated PET in rats, measurements of cardiac function are significantly affected by the frames per cardiac cycle. Therefore, if you are going to compare those functional parameters, a consistent number of frames should be used.
Purpose: Early identification of aggressive disease could improve decision-support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-PET before PRRT was analyzed.
Procedures: 31 patients with G1/G2 pNET were enrolled (G2, n=23/31). Prior to PRRT with [\(^{177}\)Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET/CT was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV\(_{mean/max}\)), imaging-based TF as well as clinical parameters (Ki67, CgA) for prediction of both progression-free (PFS) and overall survival (OS) after PRRT was evaluated.
Results: Within a median follow-up of 3.7y, tumor progression was detected in 21 patients (median, 1.5y) and 13/31 deceased (median, 1.9y). In ROC analysis, the TF Entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff=6.7, AUC=0.71, p=0.02). Of note, increasing Entropy could predict a longer survival (>6.7, OS=2.5y, 17/31), whereas less voxel-based derangement portended inferior outcome (<6.7, OS=1.9y, 14/31). These findings were supported in a G2 subanalysis (>6.9, OS=2.8y, 9/23 vs. <6.9, OS=1.9y, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using Entropy (n=31, p<0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n=31, p=0.04). Ki67 was negatively associated with PFS (p=0.002); however, SUVmean/max failed in prognostication (n.s.).
Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.
Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-targeted positron emission tomography (PET) imaging agents for staging and restaging of prostate carcinoma or neuroendocrine tumors, respectively, are seeing rapidly expanding use. In addition to diagnostic applications, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy. While interpreting PSMA- or SSTR-targeted PET/computed tomography (CT) scans, the reader has to be aware of certain pitfalls. Adding to the complexity of the interpretation of those imaging agents, both normal biodistribution, and also false-positive and -negative findings differ between PSMA- and SSTR-targeted PET radiotracers. Herein summarized under the umbrella term molecular imaging reporting and data systems (MI-RADS), two novel RADS classifications for PSMA- and SSTR-targeted PET imaging are described (PSMA- and SSTR-RADS). Both framework systems may contribute to increase the level of a reader’s confidence and to navigate the imaging interpreter through indeterminate lesions, so that appropriate workup for equivocal findings can be pursued. Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e. if the reader is familiar with one system, the other system can readily be applied as well. In the present review we will discuss the most common pitfalls on PSMA- and SSTR-targeted PET/CT, briefly introduce PSMA- and SSTR-RADS, and define a future role of the umbrella framework MI-RADS compared to other harmonization systems.
Purpose: The metabolically most active lesion in 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic \(^{18}\)F-FDG PET.
Methods: Eighteen patients with progressive MTC underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated.
Results: The TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3y (vs. low-risk group, OS=5.3y, 8/18, AUC=0.78, P=0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS=3.5y vs. low-risk group, OS=5y, 7/18, AUC=0.83, P=0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P=0.02, OS, n.s.).
Conclusions: The TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.