[Show abstract][Hide abstract] ABSTRACT: Since prostate-specific membrane antigen (PSMA) has been identified as a diagnostic target for prostate cancer, many urea-based small PSMA-targeting molecules were developed. First, the clinical application of these Ga-68 labelled compounds in positron emission tomography (PET) showed their diagnostic potential. Besides, the therapy of prostate cancer is a demanding field, and the use of radiometals with PSMA bearing ligands is a valid approach. In this work, we describe the synthesis of a new PSMA ligand, CHX-A''-DTPA-DUPA-Pep, the subsequent labelling with Ga-68, Lu-177 and Y-90 and the first in vitro characterization. In cell investigations with PSMA-positive LNCaP C4-2 cells, K D values of ≤14.67 ± 1.95 nM were determined, indicating high biological activities towards PSMA. Radiosyntheses with Ga-68, Lu-177 and Y-90 were developed under mild reaction conditions (room temperature, moderate pH of 5.5 and 7.4, respectively) and resulted in nearly quantitative radiochemical yields within 5 min.
[Show abstract][Hide abstract] ABSTRACT: Functional nanoparticles are highly interesting imaging agents for positron emission tomography (PET) due to the possibility of multiple incorporation of positron emitting radionuclides thus increasing the signal strength. Furthermore, long-term nanoparticle biodistribution tests with increased signal-to-noise ratio can be achieved with nanoparticles carrying long-lived isotopes. Mesoporous silica nanoparticles, MSNs, have recently attracted a lot of interest as both imaging agents and carriers for drugs in vitro and in vivo. Here we present results related to the synthesis of PET imageable MSNs carrying the long-lived (89)Zr isotope (half-life of 78.4 hours). Here, (89)Zr(4+) was immobilized through covalent attachment of the complexing agent p-isothiocyanatobenzyldesferrioxamine (DFO-NCS) to large-pore MSNs. Due to the presence of the high DFO content on the MSNs, quantitative (89)Zr(4+) labeling was achieved within just a few minutes, and no subsequent purification step was needed in order to remove non-complexed (89)Zr(4+). The stability of the (89)Zr-labeled MSNs against leaching of (89)Zr(4+) was verified for 24 hours. The high signal strength of the (89)Zr-DFO-MSNs was evidenced by successful PET imaging using a mouse model at particle loadings one order of magnitude lower than those previously applied in PET-MSN studies. The biodistribution followed the same trends as previously observed for MSNs of different sizes and surface functionalities. Taken together, our results suggest that (89)Zr-DFO-MSNs are promising PET imaging agents for long-term in vivo imaging.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To evaluate the diagnostic accuracy of choline-PET/CT for nodal relapse of prostate cancer (PCA) according to topographical location and the size of tumor infiltration in lymph nodes (LN).
72 patients with nodal PCA-relapse after primary therapy underwent pelvic and/or retroperitoneal salvage lymph node dissection (salvage-LND) after a whole body PET/CT with 11C-Choline or 18F-Fluoroethylcholine showing PET-positive LN but no other detectable metastases. Diagnostic accuracy was evaluated for 160 dissected LN-regions (pelvic left/right, retroperitoneal), 498 subregions (common,-external,-internal-iliac, obturatoria, presacral, aortic-bifurcation, aortal, caval, interaortocaval) and 2122 LNs.
Lymph node metastases (LNM) were present in 32% of the resected LN (681/2122) resulting in 238 positive subregions and 111 positive regions. PET/CT was positive for 110 regions and 209 subregions. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were: region-based 91.9%, 83.7%, 92.7%, 82.0% and 89.4%, subregion-based 80.7%, 93.5%, 91.9%, 84.1% and 87.3%, lesion-based 57.0%, 98.4%, 94.5%, 82.6% and 84.9%. 70.7% (278/393) of true positive LNM detected by PET/CT were located in LN with a short axis diameter <10mm. Sensitivity of choline-PET/CT was 13.3%, 57.4% and 82.8% for depth of tumor infiltration of ≥2-<3mm, ≥5-<6mm and ≥10-<11mm, respectively. Location of LNM and radiotracer (11C-choline/18F-fluoroethylcholine) had no substantial impact on diagnostic accuracy.
Choline-PET/CT detects affected LN-regions (left/right pelvic, retroperitoneal) in PCA-relapse with high accuracy and seems helpful for guiding salvage-LND. Sensitivity of choline-PET/CT decreases with the size of metastatic infiltration in LNs. Choline-PET/CT detects metastases in a significant fraction of LNs that are not pathologically enlarged on CT.
The Journal of urology 01/2014; · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since prostate-specific membrane antigen (PSMA) has been identified as a diagnostic target for prostate cancer, many urea-based small PSMA-targeting molecules were developed. First, the clinical application of these Ga-68 labelled compounds in positron emission tomography (PET) showed their diagnostic potential. Besides, the therapy of prostate cancer is a demanding field, and the use of radiometals with PSMA bearing ligands is a valid approach. In this work, we describe the synthesis of a new PSMA ligand, CHX-A''-DTPA-DUPA-Pep, the subsequent labelling with Ga-68, Lu-177 and Y-90 and the first in vitro characterization. In cell investigations with PSMA-positive LNCaP C4-2 cells, KD values of ≤14.67 ± 1.95 nM were determined, indicating high biological activities towards PSMA. Radiosyntheses with Ga-68, Lu-177 and Y-90 were developed under mild reaction conditions (room temperature, moderate pH of 5.5 and 7.4, respectively) and resulted in nearly quantitative radiochemical yields within 5 min.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND:: Focused unilateral or minimally invasive parathyroidectomy for primary hyperparathyroidism (pHPT) depends on the successful preoperative localization of parathyroid adenomas. The aim of this prospective study was to determine the accuracy of C-11 methionine positron emission tomography/computed tomography (Met-PET/CT), a novel localization procedure for hyperfunctional parathyroid tissue. METHODS:: Preoperative Met-PET/CT scans of the neck and mediastinum of 102 patients undergoing parathyroidectomy for pHPT were preoperatively evaluated by a radiologist and a nuclear medicine physician and prospectively documented. The results of Met-PET/CT were compared with intraoperative and histopathological findings. RESULTS:: pHPT was caused by a single-gland adenoma in 97 patients, whereas 5 patients had multiglandular disease. Met-PET/CT correctly located a single-gland adenoma in 83 of 97 (86%) patients with pHPT (sensitivity 91%). The positive predictive value of Met-PET/CT in localizing a single-gland adenoma was 93%. Of the 5 patients with multiglandular disease, Met-PET/CT identified 2 hyperfunctioning parathyroid glands in 1 patient, 1 gland in 3 individuals, and was negative in the fifth patient (sensitivity 80%). A highly significant correlation was observed between true-positive findings and the size (mean = 1.81 ± 0.84 cm) and weight (mean = 1.50 ± 2.56 g) of parathyroid adenoma, whereas patients with false-negative findings had significantly smaller (mean = 1.09 ± 0.41 cm) and lighter (mean = 0.37 ± 0.29 g) glands (P < 0.001 and P = 0.001, respectively). CONCLUSIONS:: This study demonstrates the high accuracy of Met-PET/CT in the preoperative localization of parathyroid adenomas in a large series of patients with pHPT.
[Show abstract][Hide abstract] ABSTRACT: Die molekulare Bildgebung mit FDG-PET/CT stellt ein wertvolles Instrument zur Tumorlokalisation, Ausbreitungsdiagnostik und Therapiekontrolle dar. International ist ein breites Indikationsspektrum etabliert, während das deutsche Gesundheitssystem eine deutlich restriktivere Position vertritt. Die Translation innovativer Bildgebungsansätze in die klinische Medizin ist ohne geeignete Förder und Evaluationsinstrumente problematisch.
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: We evaluated the impact of salvage lymph node dissection with adjuvant radiotherapy in patients with nodal recurrence of prostate cancer. By default, nodal recurrence of prostate cancer is treated with palliative antihormonal therapy, which causes serious side effects and invariably leads to the development of hormone refractory disease. MATERIALS AND METHODS: A total of 47 patients with nodal recurrence of prostate cancer based on evidence of (11)C-choline/(18)F-choline ((18)F-fluorethylcholine) positron emission tomography-computerized tomography underwent primary (2 of 52), secondary (45 of 52), tertiary (4 of 52) and quaternary (1 of 52) salvage lymph node dissection with histological confirmation. Of 52 salvage lymph node dissections 27 were followed by radiotherapy. Biochemical response was defined as a prostate specific antigen less than 0.2 ng/ml after salvage therapy. The Kaplan-Meier method, binary logistic regression and Cox regression were used to analyze survival as well as predictors of biochemical response and clinical progression. RESULTS: Mean prostate specific antigen at salvage lymph node dissection was 11.1 ng/ml. A mean of 23.3 lymph nodes were removed per salvage lymph node dissection. Median followup was 35.5 months. Of 52 salvage lymph node dissections 24 resulted in complete biochemical response followed by 1-year biochemical recurrence-free survival of 71.8%. Gleason 6 or less (OR 7.58, p = 0.026), Gleason 7a/b (OR 5.91, p = 0.042) and N0 status at primary therapy (OR 8.01, p = 0.011) were identified as independent predictors of biochemical response. Gleason 8-10 (HR 3.5, p = 0.039) as a preoperative variable, retroperitoneal positive lymph nodes (HR 3.76, p = 0.021) and incomplete biochemical response (HR 4.0, p = 0.031) were identified as postoperative predictors of clinical progression. Clinical progression-free survival was 25.6% and cancer specific survival was 77.7% at 5 years. CONCLUSIONS: Based on (11)C/(18)F-choline positron emission tomography-computerized tomography as a diagnostic tool, salvage lymph node dissection is feasible for the treatment of nodal recurrence of prostate cancer. Most patients experience biochemical recurrence after salvage lymph node dissection. However, a specific population has a lasting complete prostate specific antigen response.
The Journal of urology 10/2012; · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: [11C]Choline-positron emission tomography in combination with computer tomography ([11C]Choline-PET/CT) is a promising imaging approach for localizing relapsing prostate cancer. We therefore studied performance of [11C]Choline-PET/CT in patients relapsing from prostate cancer after radical prostatectomy (RP) and scheduled for salvage radiation therapy (SRT) in terms of relapse localization and relationship to outcome after SRT.
In a prospective pilot study we examined 27 patients with [11C]Coline-PET/CT before SRT. All patients had biochemical relapse after RP and were treated with SRT. [11C]Choline-PET/CT was done within 14 days before SRT.
Eleven of 27 patients had at follow up of 76.5±5.7 months a favorable long-term response to SRT and needed no specific further prostate cancer related treatment. In 16/27 patients, rising serum PSA concentrations were observed 34.2±20.1 months after SRT, qualifying them as treatment failures. Tumor stage, risk profile and PSA before SRT were not different in long term responders and failures. [11C]Choline-PET/CT showed local relapse in about 50% of both long-term responders failures, locoregional nodal relapse in 4/16 failures and a singular bone metastasis in 1/16 failures.
[11C]Choline-PET/CT showed in roughly 50% of patients evidence of local relapse within the prostatic fossa. Roughly 30% of treatment failures had evidence of locoregional nodal or distant metastatic disease outside the radiation ports possibly related to treatment failures after SRT. Kaplan-Meier analysis suggested that [11C]Choline-PET/CT positive patients do worse at follow-up in terms of freedom from biochemical recurrence.
The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... 10/2012; 56(5):430-9. · 1.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An important assumption in dosimetry prior to radionuclide therapy is the equivalence of pretherapeutic and therapeutic biodistribution. In this study the authors investigate if this assumption is justified in sst2-receptor targeting peptide therapy, as unequal amounts of peptide and different peptides for pretherapeutic measurements and therapy are commonly used.
Physiologically based pharmacokinetic models were developed. Gamma camera and serum measurements of ten patients with metastasizing neuroendocrine tumors were conducted using (111)In-DTPAOC. The most suitable model was selected using the corrected Akaike information criterion. Based on that model and the estimated individual parameters, predicted and measured (90)Y-DOTATATE excretions during therapy were compared. The residence times for the pretherapeutic (measured) and therapeutic scenarios (simulated) were calculated.
Predicted and measured therapeutic excretion differed in three patients by 10%, 31%, and 7%. The measured pretherapeutic and therapeutic excretion differed by 53%, 56%, and 52%. The simulated therapeutic residence times of kidney and tumor were 3.1 ± 0.6 and 2.5 ± 1.2 fold higher than the measured pretherapeutic ones.
To avoid the introduction of unnecessary inaccuracy in dosimetry, using the same substance along with the same amount for pretherapeutic measurements and therapy is recommended.
Medical Physics 09/2012; 39(9):5708-17. · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) is able to localize persistent or recurrent disease in differentiated thyroid carcinoma (DTC). The aim of the study was to correlate PET/CT results with precise intraoperative localization of persistent or recurrent papillary and follicular thyroid carcinoma. Patients with differentiated thyroid carcinoma who received FDG-PET scans were prospectively documented. The PET/CT results were correlated with other localization studies (neck ultrasound, 131I whole-body scan) and accurately compared to intraoperative findings and histopathological examinations. FDG-PET/CT scans were performed in 18 patients, between 16 and 84 years of age, from December 2008 to June 2011. Fourteen patients had papillary thyroid carcinomas and 4 had follicular thyroid carcinomas. All patients had a previous thyroidectomy and radioiodine ablation. Before cervical re-exploration, FDG-PET/CT-positive findings were reported in 14 individuals, whereas 4 PET scans provided no evidence of disease. Intraoperatively, 13 of 14 FDG-PET/CT-positive localizations of recurrent or persistent thyroid carcinomas were verified and confirmed by histopathology (sensitivity 93%). In another patient lymph node metastases of lung cancer were detected intraoperatively. However, FDG-PET/CT underestimated the number of lesions in 5 of 6 patients undergoing systematic lymphadenectomy. No lymph node or soft tissue metastases were found intraoperatively in 3 of the 4 patients with negative FDG-PET scans. A solitary cystic lymph node metastasis was found in the fourth patient but was not detected by FDG-PET/CT (specificity 75%). FDG-PET/CT has high sensitivity and specificity for the detection of persistent or recurrent differentiated thyroid carcinoma. FDG-PET/CT helps to select patients who might benefit from surgery because it provides precise anatomical details.
Hormone and Metabolic Research 07/2012; · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A rapid and efficient n.c.a. radiosynthesis of 6-[(11)C]methyldopamine ([(11)C]MeDA) using the Stille cross-coupling reaction as a key step was developed. The labeling conditions for the formation of the intermediate compound (protected [(11)C]MeDA, [(11)C]7) were determined with respect to reaction temperature and time. The radiochemical yield 89 ± 1.4% (decay-corrected) of the protected intermediate [(11)C]7 was obtained at a reaction temperature of 60°C and a reaction time of 5 min using Pd(2)(dba)(3)/P(o-tolyl)(3) and CsF/CuBr as a co-catalyst system. The overall yield after deprotection with 45% HBr at 140°C for 10 min was 64 ± 3.9% (decay-corrected) within a total preparation time of 40 min, including hydrolysis, HPLC purification and formulation.
Applied radiation and isotopes: including data, instrumentation and methods for use in agriculture, industry and medicine 05/2012; 70(8):1475-9. · 1.09 Impact Factor