SUVmean ratios of liver/muscle and lung/muscle from 13N-NH3 PET perfusion outperformed traditional myocardial viability parameters in predicting survival after CABG.

PURPOSE: Myocardial viability evaluation in predicting survival after coronary artery bypass graft (CABG) remains debatable. Thus, this study aimed to investigate the role of 13N-NH3/18F-FDG PET myocardial viability scan in predicting treatment outcomes and survival. METHODS: 90 patients with CABG and pre-surgical PET-based myocardial viability scan were retrospectively reviewed. Perfusion-metabolism features, myocardium motion parameters, and patient characteristics were recorded. Additionally, the SUVmean of blood pool, lung, liver, spleen, and muscle were measured and the SUVmean ratios were calculated. Factors associated with treatment outcomes and survival were analyzed by Logistic and Cox regressions. Nomogram models were subsequently established to predict ejection fraction (EF) improvement and survival outcomes. RESULTS: The mean EF of these 90 patients was 38.1 ± 9.5% and 46.0 ± 9.2% before and after CABG surgery, and 35 patients (38.9%) achieved EF improvement ≥ 10%. EF measurements by PET and echocardiogram showed a reasonable linear correlation (R = 0.752). Sex, pre-surgical EF, mismatch of the left ventricle, total perfusion deficit (TPD), and peak ejection rate (PER) were independent predictive factors of EF improvements. Surgery waiting time, valve damage, and SUVmean ratio of Liver/Muscle were independently predictive of event-free survival (EFS), while valve damage, together with SUVmean ratio of either Liver/Muscle or Lung/Muscle, were independently predictive of overall survival (OS). CONCLUSION: Although traditional cardiac parameters from PET-based myocardial viability can effectively predict EF improvements after CABG, SUVmean ratios of liver/muscle and lung/muscle from 13N-NH3 PET perfusion outperformed these parameters in predicting survival.

11C-CFT PET brain imaging in Parkinson's disease using a total-body PET/CT scanner.

PURPOSE: This study aimed to evaluate the feasibility of 11C-CFT PET brain imaging in Parkinson's Disease using a total-body PET/CT scanner and explore the optimal scan duration to guide the clinical practice. METHODS: Thirty-two patients with Parkinson's disease (PD) performing 11C-CFT PET/CT brain imaging using a total-body PET/CT scanner were retrospectively enrolled. The PET data acquired over a period of 900 s were reconstructed into groups of different durations: 900-s, 720-s, 600-s, 480-s, 300-s, 180-s, 120-s, 60-s, and 30-s (G900 to G30). The subjective image quality analysis was performed using 5-point scales. Semi-quantitative measurements were analyzed by SUVmean and dopamine transporter (DAT) binding of key brain regions implicated in PD, including the caudate nucleus and putamen. The full-time images (G900) were served as reference. RESULTS: The overall G900, G720, and G600 image quality scores were 5.0 ± 0.0, 5.0 ± 0.0, and 4.9 ± 0.3 points, respectively, and there was no significant difference among these groups (P > 0.05). A significant decrease in these scores at durations shorter than 600 s was observed when compared to G900 images (P < 0.05). However, all G300 image quality was clinically acceptable (≥ 3 points). As the scan duration reduced, the SUVmean and DAT binding of caudate nucleus and putamen decreased progressively, while there were no statistically significant variations in the SUVmean of the background among the different groups. Moreover, the changes in the lesion DAT binding (ΔDAT-binding) between the full-time reference G900 image and other reconstructed group G720 to G30 images generally increased along with the reduced scan time. CONCLUSION: Sufficient image quality and lesion conspicuity could be achieved at 600-s scan duration for 11C-CFT PET brain imaging in PD assessment using a total-body PET/CT scanner, while the image quality of G300 was acceptable to meet clinical diagnosis, contributing to improve patient compliance and throughput of PET brain imaging.

Case report: Uncommon multiple metastases from occult breast cancer revealed by 68Ga-DOTATATE PET/CT.

Occult breast cancer is an uncommon type of breast cancer and its diagnosis is challenging. It is usually invisible on multiple imaging examines. Metastases to the rectum and inguinal lymph nodes from occult breast lobular cancer are even rarer. 68Ga-DOTA peptides can image neuroendocrine tumors by targeting specific somatostatin receptors. Besides, other tumors, including breast cancer, have been shown to express somatostatin receptors. In this case, we presented a 63-year-old woman who underwent both 18F-FDG and 68Ga-DOTATATE PET/CT due to a rectal polyp. An endoscopic excision biopsy confirmed metastatic carcinoma of suspected breast origin, but subsequent ultrasound and MRI showed no signs of malignancy in the breast and adnexa uteri. PET/CT showed obvious 68Ga-DOTATATE activity in bilateral axillary and right inguinal lymph nodes with mild 18F-FDG uptake. Final histopathology at the left axillary, right inguinal lymph nodes, and rectum indicated metastases from breast cancer while the origin remained radiologically occult. Additionally, one uterine fibroids was found with positive uptake of 68Ga-DOTATATE and negative uptake of 18F-FDG. This case suggested that 68Ga-DOTATAE PET/CT may be an effective supplement in diagnosing OBC lymph node metastases with mild 18F-FDG uptake, and it may provide a new technology for the clinical diagnosis of occult breast cancer.

Rational Design, Synthesis and Preliminary Evaluation of Novel Fusarinine C-Based Chelators for Radiolabeling with Zirconium-89.

Fusarinine C (FSC) has recently been shown to be a promising and novel chelator for 89Zr. Here, FSC has been further derivatized to optimize the complexation properties of FSC-based chelators for 89Zr-labeling by introducing additional carboxylic groups. These were expected to improve the stability of 89Zr-complexes by saturating the 8-coordination sphere of [89Zr] Zr4+, and also to introduce functionalities suitable for conjugation to targeting vectors such as monoclonal antibodies. For proof of concept, succinic acid derivatization at the amine groups of FSC was carried out, resulting in FSC(succ)2 and FSC(succ)3. FSC(succ)2 was further derivatized to FSC(succ)2 AA by reacting with acetic anhydride (AA). The Zr4+ complexation properties of these chelators were studied by reacting with ZrCl4. Partition coefficient, protein binding, serum stability, acid dissociation, and transchelation studies of 89Zr-complexes were carried out in vitro and the results were compared with those for 89Zr-desferrioxamine B ([89Zr]Zr-DFO) and 89Zr-triacetylfusarinine C ([89Zr]Zr-TAFC). The in vivo properties of [89Zr]Zr-FSC(succ)3 were further compared with [89Zr]Zr-TAFC in BALB/c mice using micro-positron emission tomography/computer tomography (microPET/CT) imaging. Fusarinine C (succ)2AA and FSC(succ)3 were synthesized with satisfactory yields. Complexation with ZrCl4 was achieved using a simple strategy resulting in high-purity Zr-FSC(succ)2AA and Zr-FSC(succ)3 with 1:1 stoichiometry. Distribution coefficients of 89Zr-complexes revealed increased hydrophilic character compared to [89Zr]Zr-TAFC. All radioligands showed high stability in phosphate buffered saline (PBS) and human serum and low protein-bound activity over a period of seven days. Acid dissociation and transchelation studies exhibited a range of in vitro stabilities following the order: [89Zr]Zr-FSC(succ)3 > [89Zr]Zr-TAFC > [89Zr]Zr-FSC(succ)2AA >> [89Zr]Zr-DFO. Biodistribution studies of [89Zr]Zr-FSC(succ)3 revealed a slower excretion pattern compared to [89Zr]Zr-TAFC. In conclusion, [89Zr]Zr-FSC(succ)3 showed the best stability and inertness. The promising results obtained with [89Zr]Zr-FSC(succ)2AA highlight the potential of FSC(succ)2 as a monovalent chelator for conjugation to targeted biomolecules, in particular, monoclonal antibodies.

Preclinical evaluation of 5-([11C]-methyloxy)-L-tryptophan as a potential PET molecular imaging probe.

OBJECTIVE: The new tumor probe 5-([C]-methyloxy)-L-tryptophan ([C]-L-CMTP) had been found to show high uptake in tumor tissue in our previous report; however, the pharmacokinetic properties of [C]-L-CMTP have not been characterized. In this present study, we evaluated the potential of [C]-L-CMTP as a PET probe for tumor imaging. METHODS: The biodistribution of [C]-L-CMTP was determined in healthy mice and the incorporation of [C]-L-CMTP into proteins was investigated. In-vitro competitive inhibition experiments were conducted with Hepa1-6 hepatoma cell lines. [C]-L-CMTP PET imaging was performed on S180 tumor-bearing mice and lung tumor-bearing mice. RESULTS: Biodistribution studies showed high uptake of [C]-L-CMTP in the liver, kidney, and pancreas, but low uptake in brain. The transport assay studies in Hepa1-6 cells suggested that [C]-L-CMTP was mainly transported by the amino acid transport system B and LAT1. [C]-L-CMTP was not incorporated into proteins in vitro. PET imaging showed that [C]-L-CMTP had high uptake in S180 fibrosarcoma tumor and lung tumor. CONCLUSION: [C]-L-CMTP was not incorporated into proteins and was mainly transported by the amino acid transport system B and LAT1, PET imaging showed that [C]-L-CMTP had high uptake in tumor models; it seemed to be a promising PET probe for tumor by LAT1 transport. Video abstract: http://links.lww.com/NMC/A70.

18F-FP-PEG2-ß-Glu-RGD2: A Symmetric Integrin αvß3-Targeting Radiotracer for Tumor PET Imaging.

Radiolabeled cyclic arginine-glycine-aspartic (RGD) peptides can be used for noninvasive determination of integrin αvß3 expression in tumors. In this study, we performed radiosynthesis and biological evaluation of a new 18F-labeled RGD homodimeric peptide with one 8-amino-3,6-dioxaoctanoic acid (PEG2) linker on the glutamate ß-amino group (18F-FP-PEG2-ß-Glu-RGD2) as a symmetric PET tracer for tumor imaging. Biodistribution studies showed that radioactivity of 18F-FP-PEG2-ß-Glu-RGD2 was rapidly cleared from blood by predominately renal excretion. MicroPET-CT imaging with 18F-FP-PEG2-ß-Glu-RGD2 revealed high tumor contrast and low background in A549 human lung adenocarcinoma-bearing mouse models, PC-3 prostate cancer-bearing mouse models, and orthotopic transplanted C6 brain glioma models. 18F-FP-PEG2-ß-Glu-RGD2 exhibited good stability in vitro and in vivo. The results suggest that this tracer is a potential PET tracer for tumor imaging.

[Radiosynthesis and preliminary evaluation of 5-([11C]methyloxy)-L-tryptophan as PET tumor imaging].

The PET tracer 5-([11C]methyloxy)-L-tryptophan (5-(11)CMTP) was prepared by nucleophilic fluorination and alkylation reaction via a two-step procedure in order to develop specific tumor probe. The biodistribution and microPET imaging of 5-(11)CMTP were executed. The results unveiled that the overall radiochemical yield with no decay correction was (14.6 ±7.2) %, the radiochemical purity was more than 95% and high uptake and long retention time of 5-(11)CMTP in liver, kidney and blood were observed but low uptake in brain and muscle were found, furthermore, high uptake of 5-(11)CMTP in tumor tissue was observed. It seems that 5-(11)CMTP will be a potential amino acid tracer for tumors imaging with PET.

Synthesis and biological evaluation of N-(2-[(18)F]Fluoropropionyl)-L-methionine for tumor imaging.

INTRODUCTION: N-position radiolabeled amino acids, such as N-(2-[(18)F]fluoropropionyl)-L-methionine ([(18)F]FPMET) as a derivative of L-methionine (MET), can potentially serve as a PET tracer for tumor imaging. In the current study, radiosynthesis and biological evaluation of [(18)F]FPMET as a new PET tumor agent are performed. METHODS: [(18)F]FPMET was synthesized by reacting 4-nitrophenyl 2-[(18)F]fluoropropionate ([(18)F]NFP) with MET. In vitro competitive inhibition and protein incorporation experiments were performed with Hepa1-6 hepatoma cell lines. The biodistribution of [(18)F]FPMET was determined in S180 fibrosarcoma-bearing mice. PET/CT studies of [(18)F]FPMET were conducted in S180 fibrosarcoma-bearing mice, A549 lung adenocarcinoma-bearing nude mice, and PC-3 prostate cancer-bearing nude mice. RESULTS: [(18)F]FPMET was synthesized in 72%± 4% uncorrected radiochemical yield (n=10) from [(18)F]NFP. In vitro experiments showed that [(18)F]FPMET was primarily transported through Na(+)-dependent system A, system ASC, and system B(0,+), and was not incorporated into protein. Biodistribution and PET/CT imaging studies indicated that [(18)F]FPMET could delineate S180 fibrosarcoma, A549 lung adenocarcinoma, and PC-3 prostate cancer. CONCLUSION: An efficient synthesis of N-position [(18)F]labeled amino acids with a classic [(18)F]NFP prosthetic group is developed. The results support that [(18)F]FPMET seems to be a potential tracer for tumor imaging with PET.

Radiosynthesis and biological evaluation of 5-(3-[18F]fluoropropyloxy)-L-tryptophan for tumor PET imaging.

INTRODUCTION: [(18)F]FDG PET has difficulty distinguishing tumor from inflammation in the clinic because of the same high uptake in nonmalignant and inflammatory tissue. In contrast, amino acid tracers do not accumulate in inflamed tissues and thus provide an excellent opportunity for their use in clinical cancer imaging. In this study, we developed a new amino acid tracer 5-(3-[(18)F]Fluoropropyloxy)-L-tryptophan ([(18)F]-L-FPTP) by two-step reactions and performed its biologic evaluation. METHODS: [(18)F]-L-FPTP was prepared by [(18)F]fluoropropylation of 5-hydroxy-L-tryptophan disodium salt and purification on C18 cartridges. The biodistribution of [(18)F]-L-FPTP was determined in normal mice and the incorporation of [(18)F]-L-FPTP into tissue proteins was investigated. In vitro competitive inhibition experiments were performed with Hepa1-6 hepatoma cell lines. [(18)F]-L-FPTP PET imaging was performed on tumor-bearing and inflammation mice and compared with [(18)F]-L-FEHTP PET. RESULTS: The overall uncorrected radiochemical yield of [(18)F]-L-FPTP was 21.1 ± 4.4% with a synthesis time of 60 min, the radiochemical purity was more than 99%. Biodistribution studies demonstrate high uptake of [(18)F]-L-FPTP in liver, kidney, pancreas, and blood at the early phase, and fast clearance in most tissues over the whole observed time. The uptake studies in Hepa1-6 cells suggest that [(18)F]-L-FPTP is transported by the amino acid transport system B(0,+), LAT2 and ASC. [(18)F]-L-FPTP displays good stability and is not incorporated into proteins in vitro. PET imaging shows that [(18)F]-L-FPTP can be a better potential PET tracer for differentiating tumor from inflammation than [(18)F]FDG and 5-(3-[(18)F]fluoroethyloxy)-L-tryptophan ([(18)F]-L-FEHTP), with high [(18)F]-L-FPTP uptake ratio (2.53) of tumor to inflammation at 60 min postinjection. CONCLUSIONS: Using [(18)F]fluoropropyl derivatives as intermediates, the new tracer [(18)F]-L-FPTP was achieved with good yield and radiochemical purity, and the biological evaluation results of [(18)F]-L-FPTP showed that it was a hopeful tracer for PET tumor imaging.

[Positron emission tomography with L-[S-methyl-11C]-methioine and its biodistribution].

OBJECTIVE: To study the biodistribution of L-[S-methyl-(11)C]-methioine ((11)C-MET) and explore its clinical application in positron emission tomography (PET) for brain tumor detection. METHODS: Twenty-four Wistar rats and divided into 6 equal groups and injected with (11)C-MET through the tail vein and killed by decollation at 5, 10, 20, 30 and 40 min after injection, respectively. The liver, brain, blood, heart, lung, kidney, and spleen were harvested to measure the radioactivity and calculate the biodistribution of (11)C-MET. PET imaging with (11)C-MET was performed in 6 normal volunteers and 30 patients with pathologically confirmed brain gliomas. RESULTS AND CONCLUSION: (11)C-MET showed high blood uptake and a long retention in the tumor mass, therefore can be a valuable tracer for PET imaging of brain tumor and the hypophysis.