The value of dual probes in tracerpositron emission tomography/magnetic resonance imaging in the grading diagnosis of pancreatic neuroendocrine neoplasms / 中华消化杂志

Objective:To explore the diagnostic and grading value of combination of 68Ga -1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide ( 68Ga-DOTA-TATE) and 18F-flurodeoxyglucose ( 18F-FDG) dual probes in multi-parameter positron emission tomography (PET)/magnetic resonance (MR) imaging in pancreatic neuroendocrine neoplasm (PNEN). Methods:From April 9th, 2020 to February 24th, 2022, in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, the clinical data and the imaging of 68Ga-DOTA-TATE PET/MR and 18F-FDG PET/MR of 59 patients with pancreatic tumors (27 male, 32 female, aged 22 to 75 years old(51.8±13.3) years old), confirmed by surgical or biopsy pathology were retrospectively analyzed. All the cases were divided into PNEN group (42 cases) and non-PNEN group (17 cases) according to pathological results. Among which 39 patients with PNET were further divided into grade 1 group (G1 group, 27 cases) and grade 2 group (G2 group, 12 cases). Non-zero parameters were selected via the least absolute shrinkage and selection operator (LASSO) regression approach, and a logistic regression model was established by combination of the selected features and the corresponding non-zero coefficients. The measurement data with non-normal distribution were compared by Mann-Whitney U test. The receiver operating characteristic (ROC) curve were used to detemine the optimal cut off value to assess the dignostic efficiency. Results:Compared with those of non-PNEN group, the parameters of PNEN group increased, which included maximum standard uptake value of 68Ga-DOTA-TATE(SUV Gmax, 46.70 (22.37, 76.35) vs. 7.12 (4.75, 8.64)), mean standard uptake value of 68Ga-DOTA-TATE(SUV Gmean, 25.50 (13.18, 43.90) vs. 3.65 (2.89, 4.69)), peak standard uptake value of 68Ga-DOTA-TATE (SUV Gpeak, 27.17 (12.39, 46.97) vs. 5.46 (4.12, 6.56)), total lesion somatostatin receptor (SSR) expression (TLSRE, 68.21 (32.52, 440.96) vs. 26.02 (14.87, 69.57)), SUV Gmax/maximum standard uptake value of 18F-FDG (SUV Fmax, 12.71 (3.80, 21.70) vs. 1.10 (0.52, 2.35)), tumor to background ratio of 68Ga-DOTA-TATE (TBR G, 13.31 (5.54, 22.38) vs. 1.57 (1.31, 2.66)), tumor to liver ratio of 68Ga-DOTA-TATE(T/L G, 6.54 (2.90, 9.63) vs. 0.74 (0.65, 0.94)), tumor to spleen ratio of 68Ga-DOTA-TATE (T/S G, 2.36 (0.97, 3.70) vs. 0.25 (0.23, 0.38)), tumor to mediastinum ratio of 68Ga-DOTA-TATE (T/M G, 104.41 (34.03, 206.52) vs. 16.00 (12.87, 21.46)), SUV Gmax/minimum apparent diffusion coeffecient (ADC min, 55.14 (22.50, 96.37) vs. 6.76 (4.39, 12.76)) and SUV Gmean/ADC min (34.57 (13.47, 55.13) vs. 3.57 (2.46, 6.81)), and the differences were statistically significant ( U=28.00, 25.00, 32.00, 198.00, 54.00, 31.00, 28.00, 19.00, 10.00, 56.00 and 44.00, all P<0.01). The area under the curve (AUC) and diagnostic accuracy of dual-probe PET/MR imaging in the diagnosis of PNEN and non-PNEN were 0.941 and 96.6%, respectively. The AUC and diagnostic accuracy of model Y 1 in the diagnosis of PNEN and non-PNEN were 0.959 and 96.6%, respectively. There was no significant difference in AUC between model Y 1 and dual-probe PET/MR imaging in PNEN diagnosis ( P>0.05), however combining model Y 1 could improve the accuracy of PNEN diagnosis (100.0%). Compared with those of PNET G1 group, the parameters of G2 Group were higher, which included the maximum diameter of tumor (2.69 cm (2.08 cm, 5.00 cm) vs. 1.50 cm (1.20 cm, 2.50 cm)), metabolic tumor volume (MTV, 7.56 mL (4.45 mL, 53.57 mL) vs. 2.16 mL (1.22 mL, 5.48 mL)), total lesion glycolysis (TLG, 22.24 (11.95, 189.85) vs. 3.81 (2.11, 18.67)), tumor to background ratio of 18F-FDG (TBR F, 2.94 (2.00, 3.96) vs. 1.48 (1.29, 3.72)), tumor to liver ratio of 18F-FDG (T/L F, 2.32 (1.35, 2.98) vs. 1.08 (0.90, 2.17)) and SSR-expressing tumor volume (SRETV, 8.00 (3.06, 40.00) vs. 1.91 (0.95, 4.88)), and the differences were statistically significant ( U=66.00、66.00、77.00、93.00、90.00、65.50, all P<0.05). The maximum diameter of tumor was the best single parameter for the differential diagnosis of PNET G2 and G1, AUC was 0.796 and the cutoff value was 1.90 cm. The model Y 2, which combined the maximum diameter of tumor and TBR G had an AUC of 0.835 for the differential diagnosis of PNET G2 and G1. There was no significant difference in AUC between the maximum diameter of tumor and model Y 2 ( P>0.05). However the combination of the maximum diameter of tumor and model Y 2 could improve the accuracy of differential diagnosis of PNET G2 and G1 (94.87%). Conclusion:The combination of multi-parameter of 68Ga-DOTA-TATE and dual-probe 18F-FDG PET/MR imaging can improve the diagnostic and grading accuracy of PNEN, which may be helpful in the selection of clinical treatment for patients.

Estimation of renal absorbed doses in the treatment of neuroendocrine tumors using 177Lu-DOTA-TATE / 中华放射医学与防护杂志

Objective:To estimate the renal absorbed dose in the treatment of neuroendocrine tumors using 177Lu-DOTA-TATE and to assess the radiation safety and guide the treatment. Methods:The dosimetric calculations of patients treated with 177Lu-DOTA-TATE were carried out based on planar images of single photon emission computed tomography (SPECT). The regions of interest (ROIs) of the whole body and kidneys were delineated and converted into activity. Accordingly, the time-activity curves of the ROIs were obtained. The effective half-lives and cumulative activity of ROIs were calculated through the fitting of a single exponential equation of the ROIs. Then the absorbed doses were calculated based on the medical internal radiation dosimetry (MIRD) formalism. Results:A total of 11 patients with neuroendocrine tumors received 18 cycles of treatments with 177Lu-DOTA-TATE. The effective half-lives of 177Lu-DOTA-TATE in the whole body and kidneys were 20.0-99.8 h and 38.2-75.2 h, respectively, with an average of (57.3 ± 21.4) h and (53.1 ± 12.5) h, respectively. The renal absorbed doses of 177Lu-DTA-TATE were 0.25-1.48 mGy/MBq, with an average of (0.90 ± 0.31) mGy/MBq. The minimum and maximum renal absorbed doses in a single treatment cycle were 1.8 Gy and 9.6 Gy, respectively, while the maximum renal absorbed dose in multiple treatment cycles was 21.7 Gy. Conclusions:The renal absorbed doses in the treatment of neuroendocrine tumors using 177Lu-DOTA-TATE were estimated. The result indicate that the renal absorbed doses were lower than the tolerable dose limits. This study is expected to guide the precise treatment of neuroendocrine tumors.

Utilidad de la tomografía por emisión de positrones/ tomografía computada (PET/CT) en pacientes con diagnóstico de meduloblastoma / Usefulness of Positron Emission Tomography/Computed Tomography (PET/CT) in Patients Diagnosed with Medulloblastoma

Resumen: La tomografía por emisión de positrones/tomografía computada (PET/CT) por sus siglas en inglés, es una modalidad de imagen única que proporciona evidencia in vivo de actividades tanto bioquímicas como fisiológicas en diferentes órganos y estructuras del cuerpo. El meduloblastoma es el tumor maligno más frecuente del sistema nervioso central (SNC) en pacientes pediátricos, por este motivo el PET/CT juega un papel importante en el manejo de estos pacientes ya que proporciona información sobre el grado y extensión del tumor, así como a determinar el sitio adecuado para la toma de biopsia, valorar la respuesta al tratamiento y determinar el pronóstico del paciente. Existen diferentes radiofármacos para la evaluación de los tumores de sistema nervioso central, pero se ha estudiado que el 18F-FDG (flúor-2-fluoro-2-desoxi-D-glucosa) y el 68Ga-DOTA-NOC (68Ga-DOTA0-1NaI3-octreotide) nos ayudan a evaluar y dar seguimiento a pacientes con diagnóstico de meduloblastoma. El meduloblastoma tiene una sobreexpresión de transportadores de glucosa, principalmente tipo 1 y sobreexpresión de receptores de somatostatina predominantemente tipo 2, lo cual permite que exista una gran afinidad por estos radiofármacos.

Abstract: PET/CT (positron emission tomography/computed tomography, for its acronym in English) is a unique imaging method that provides in vivo evidence of both biochemical and physiological activities of the brain, spinal cord and tumors that involve these structures. Medulloblastoma is the most common malignant tumor of the central nervous system (CNS) in pediatric patients, so PET/CT plays an important role as it provides information on the grade and extent of the tumor, as well as to determine the appropriate site for the biopsy, assessing the response to the treatment and the patient's prognosis. There are different radiopharmaceuticals for the evaluation of central nervous system tumors, but 18F FDG (Fluor-2-fluoro-2-desoxy-D-glucose) and 68Ga-DOTA-NOC (68Ga-DOTA0-1NaI3-octreotide) have been studied to help us evaluate and follow up patients diagnosed with medulloblastoma. Medulloblastoma has an overexpression of glucose transporters, mainly type 1, and an overexpression of predominantly type 2 somatostatin receptors, which allows a high affinity for these radiopharmaceuticals.

Intramastoid Phosphaturic Mesenchymal Tumor Causing Hypophosphatemic Osteomalacia Detected on ⁶⁸Ga-DOTATATE PET/CT But Not on (99m)Tc-Sestamibi and ¹⁸F-FDG Scans / 대한핵의학회잡지

⁶⁸Ga-DOTATATE uptake in mesenchymal tumors causing hypophosphatemic osteomalacia has been recently described. Herein, we present a case of ⁶⁸Ga-DOTATATE uptake in an intramastoid phosphaturic mesenchymal tumor that had not been depicted in previous (99m)Tc-Sestamibi and ¹⁸F-FDG scans. The lesion was surgically removed and the phosphorus level increased to the normal range.

Estimation of tumour volume at therapy initiation by back-extrapolating the post-therapy regression curve of tumour volume

Background: Tumour volume at therapy initiation, Vi, is rarely available in cancer patients, and the last pre-treatment tumour volume available is from previous diagnostic imaging (Vd). Therapeutic efficacy is thus evaluated by comparing tumour volume after treatment with Vd, instead of Vi, which results in underestimation of treatment efficacy. Vi, together with Vd, can also be used for estimation of the natural growth rate of tumour valuable for, e.g., screening programs, prognostication and individualised treatment planning such as chemotherapy scheduling. The aim of this work was to study the feasibility of estimating Vi by back-extrapolating the post-therapy regression of tumour volume, based on data from animal model. Methods: Nude mice bearing human neuroendocrine GOT1 tumour cell line were treated with 177Lu-DOTA-TATE. Tumour volumes were measured regularly after therapy and Vi was estimated by back-extrapolation of (a) linear and (b) exponential regression lines of the two earliest post-therapy tumour volumes and (c) the long-term exponential regression of tumour volume. The estimated Vi values (Vest) were compared with the measured volume of tumour at therapy initiation. Results: The linear regression of the two earliest post-therapy tumour volumes gave the best estimate for Vi (Vest = 0.91 Vi, p < 0.00001), compared with the exponential regression models either on short-term (Vest = 2.30 Vi, p < 0.01), or long-term (Vest = 0.93 Vi, non-significant) follow up of tumour volume after therapy. Conclusion: Back-extrapolation of the early linear regression of tumour volume after therapy gave the best estimate for tumour volume at time of therapy initiation. This estimate can be used as baseline for treatment efficacy evaluation or for estimation of the natural growth rate of tumour (together with the measured tumour volume at pre-treatment diagnostic imaging)

Impact of ⁶⁸Ga-DOTA-Peptide PET/CT on the Management of Gastrointestinal Neuroendocrine Tumour (GI-NET): Malaysian National Referral Centre Experience / 대한핵의학회잡지

PURPOSE: The National Cancer Institute is the only referral centre in Malaysia that provides ⁶⁸Ga-DOTA-peptide imaging. The purpose of this study is to determine the impact of ⁶⁸Ga-DOTA-peptide PET/CT on the management of gastrointestinal neuroendocrine tumours (GI-NET).MATERIALS AND METHODS: A cross-sectional study was performed to review the impact of ⁶⁸Ga-DOTA-peptide (⁶⁸Ga-DOTATATE or ⁶⁸Ga-DOTATOC) PET/CT on patients with biopsy-proven GI-NET between January 2011 and December 2015. Suspected NET was excluded. Demographic data, tumoral characteristics, change of disease stage, pre-PET intended management and post-PET management were evaluated.RESULTS: Over a 5-year period, 82 studies of ⁶⁸Ga-DOTA-peptide PET/CT were performed on 44 GI-NET patients. The most common primary site was the rectum (50.0%) followed by the small bowel, stomach and colon. Using WHO 2010 grading, 40.9%of patients had low-grade (G1) tumour, 22.7% intermediate (G2) and 4.5% high (G3). Of ten patients scheduled for pre-operative staging, ⁶⁸Ga-DOTA-peptide PET/CT only led to therapeutic change in three patients. Furthermore, false-negative results of ⁶⁸Ga-DOTA-peptide PET/CT were reported in one patient after surgical confirmation. However, therapeutic changes were seen in 20/36 patients (55.6%) scheduled for post-surgical restaging or assessment of somatostatin analogue (SSA) eligibility. When ⁶⁸Ga-DOTApeptide PET/CT was used for monitoring disease progress during systemic treatment (sandostatin, chemotherapy, everolimus and PRRT) in metastatic disease, impact on management modification was seen in 19/36 patients (52.8%), of which 84.2% had inter-modality change (switch to everolimus, chemotherapy or PRRT) and 15.8% had intra-modality change (increased SSA dosage).CONCLUSIONS: ⁶⁸Ga-DOTA-peptide PET/CT has a significant impact on management decisions in GI-NET patients as it can provide additional information on occult metastasis/equivocal lesions and supply the clinician an opportunity to select patients for targeted therapy.

Preparation & in vitro evaluation of 90Y-DOTA-rituximab.

Background & objectives: Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin’s lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with 90Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. Methods: Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. Results: Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with 90Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with 90Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant Kd for 90Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of 90Y-DOTA-rituximab. Interpretation & conclusions: p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90Y was carried out. In vitro studies carried out in Raji cells showed the specificity of the radiolabelled conjugate suggesting the potential uitability of the formulation as a radiopharmaceutical for therapy of NHL.

Optimal labeling conditions of 68Ga-DOTA-iNGR and its biodistribution in mice / 中华核医学与分子影像杂志

Objective To explore the optimal conditions of preparing 68Ga-DOTA-iNGR (NGR peptide containing CendR motif),to evaluate its biodistribution in normal mice and to perform microPET imaging in tumor-bearing nude mice.Methods 68Ga fresh eluent (200 μl,92.5-129.5 MBq) obtaining with 68Ge-68Ga radionuclide generator was used to label DOTA-iNGR.The optimal conditions of labeling including pH,temperature,reacting time and concentration of DOTA-iNGR were determined.Then,the in vitro and in vivo stability and octanol/water partition coefficient of 68Ga-DOTA-iNGR were further analyzed.The biodistribution in normal Kunming mice was examined at 10,20,40,60 and 120 min after injection of 68Ga-DOTA-iNGR.Nude mice bearing HT-1080 (CDl3-positive) and HT-29 (CDl3-negative) tumors were established and underwent microPET imaging at 1 h after the intravenous injection of 68Ga-DOTA-iNGR.Data were analyzed using independent-sample t test.Results The optimal conditions of labeling was mixing 2 μg DOTA-iNGR peptide with 200 μl 68Ga (92.5-129.5 MBq) at pH 4.0,temperature 90-100 ℃ for 5-10 min.Under this condition,labeling rate reached (97.5± 1.3)％.The radiochemical purity of 68Ga-DOTA-iNGR in both saline (room temperature) and mouse serum (37 C) were both above 95％ after 4 h incubation,and the radiochemical purity in urine was greater than 85％ after 1 h metabolism in vivo.The partition coefficient was-2.71±0.18.In normal mice,majority of 68Ga-DOTA-iNGR was excreted from kidneys with a rapid clearance from blood.The in vivo microPET imaging showed that 68Ga-DOTA-iNGR was remarkably accumulated in the CD13-positive HT-1080 tumor.Conclusions Labeling DOTA-iNGR with 68Ga under our condition is a simple and efficient procedure with high labeling rate and high specificity.The product 68Ga-DOTA-iNGR has high stability,ideal biodistribution,and specific binding to CD13-positive tumor,which means that it's a very promising molecular probe for noninvasively detecting CD13-positive tumor.

Application of new bifunctional chelator DOTA and its derivatives in the metal radionuclide labeled compounds / 中华核医学与分子影像杂志

DOTA and its derivatives are most widely uscd novel bifunctional chelators.They have not only mature synthesis route,but also good coordination and chelating ability.Therefore,DOTA metal complexes of DOTA-peptide conjugates are increasingly used as MRI contrast agents,radionuclide targeted imaging agents and therapeutic radiopharmaceuticals in the biomedical field.This review covers the bifunctional derivatives of DOTA,the synthesis of DOTA-peptide conjugates,and the applications of DOTA-peptide conjugate metal complexes.

Preparation of 68 Ga-DOTA-TATE and its clinical trial in neuroendocrine tumor / 中华核医学与分子影像杂志

Objective To develop an efficient and rapid method to synthesize 68 Ga?DOTA?TATE, and to perform PET/CT imaging on neuroendocrine tumor (NET) bearing mice and one patient. Methods 68GaCl3 was eluted by 0.05 mol/L HCl in 68 Ge?68 Ga generator, then added to pre?adjusted DOTA?TATE buffer, and heated for 15 min at 85 ℃, then filtered with 0.22 μm microfiltration membrane. The radiochemical purity and in vitro stability of 68 Ga?DOTA?TATE were analyzed with radio?HPLC. The biodistribution and PET/CT imaging on HT?29 colon cancer xenografts mice model were performed. After approved by Peking University Cancer Hospital Ethics Committee, a case of NET patient received 148 MBq 68 Ga?DOTA?TATE intravenous?ly, followed by a whole?body scan at 60 min post?injection. Results 68 Ga?DOTA?TATE was prepared in high radiochemical purity (>98%) and with specific activity of 55 GBq/μmol in 25 min. The tracer showed excellent in vitro stability and no acute toxicity. PET/CT imaging on mice model showed positive uptake in tumor tissues. PET/CT imaging on one NET patient showed positive uptake of 68 Ga?DOTA?TATE in primary and metastases lesions. Conclusions A rapid, high radiolabeling yield and high specific activity method to prepare 68 Ga?DOTA?TATE is established. 68 Ga?DOTA?TATE could be specifically uptaken by somatostatin receptor ( SSTR) positive NET with high affinity. It could serve as a useful tool for early diagnosis of SSTR positive NET and has clinical prospective for somatostatin?mediated targeting therapy.

An experimental research of magnetic resonance tumor targeting imaging with Gd labeled human telomerase reverse transcriptase antisense oligonucleotide (Gd-DOTA-hTERT ASON) / 中国癌症杂志

Background and purpose:Researches had indicated that about over 85%of malignant tumors highly express telomerase activity. So telomerase has become one of the important methods in the research field of tumor diagnosis and treatment. Nowadays, several reports about malignant tumor which over expresses hTERT targeting imaging with radionuclide labeled hTERT ASON had been published. In these reports, high quality of pictures can hardly be acquired because of poor anatomical and spacial resolution in nuclear imaging itself. Accordingly, in this study, we developed a method of detecting human telomerase in vivo with magnetic resonance imaging (MRI) and evaluate its feasibility. Methods:Firstly, Uniformly phosphorothioate-modified human telomerase reverse transcriptase antisense oligonucleotide (hTERT ASON) was labeled with Gd3+ through the bifunctional chelator 1, 4, 7, 10-tetraazacyclododecane-N, N’, N’’, N’’’-tetraacetic acid (DOTA) and iv vitro experiments were performed to characterize the antisense probes (for biodistribution and cellular uptake, 99mTc-DOTA-ASON was used in stead of Gd-DOTA-ASON). Then Gd-DOTA-ASON was injected intraperitoneally in pulmonary adenocarcinoma A375 nude mice tumor-bearing BALB/c for in vivo imaging using 7.0 T Micro MRI periodically, tumors and their surrounding tissues were defined as region of interest (ROI) to calculate the signal to noise ratio (SNR) of tumor to muscle using Gd-DTPA as control. Finally, immunohistochemical analysis of telomerase activity of each xenograft was operated 2 days after imaging. Results:The binding efficiency of Gd-DOTA-ASON reached was as high as 65%(63.2±2.4, n=6). And it can maintain 61%in fresh human serum and normal saline at 37℃over 24 h;A375 cells showed an uptake of 8.5%when incubated with 99mTc-DOTA-ASON;In comparing with DOTA-ASON and Gd-DTPA, cells transected with Gd-DOTA-ASON had higher SI when performed MRI with T1WI. The hTERT-expressing xenografts were obviously enhanced by Gd-DOTA-ASON at 0.5-6 h after injection and the SNR can reach 2.37, whereas obvious enhancement only could be found within 2 h after injection of Gd-DTPA. Both labeled and non-labeled antisense probes can suppress the activity of telomerase of A375 cells either in vitro or in vitro. Conclusion:Our research offers proof that Gd-DOTA-ASON can be used as tumor specific targeting MR probe for diagnosing malignant tumors with high expression of telomerase.

PET-CT: tumores de cabeza y cuello. Ensayo pictórico y revisión de la literatura / PET-CT: Head and Neck Tumors. Picture essay and literature review

La PET-CT como modalidad diagnóstica es muy útil en la evaluación anatomofisiológica de la cabeza y el cuello. Proporciona una alta sensibilidad y especificidad en la estadificación de neoplasias primarias, la respuesta al tratamiento médico o quirúrgico y la detección de recurrencias. Dichas enfermedades representan un alto impacto sobre la mortalidad y morbilidad de los pacientes. El principal objetivo de esta publicación es hacer una revisión de los hallazgos en la PET-CT de los tumores más frecuentes de cabeza y cuello, con énfasis en los procesos malignos, estudiados en nuestra institución.

PET-CT as a diagnostic modality which is very useful in the anatomical-physiological assessment of the head and neck. It provides high sensitivity and specificity in the staging of primary tumors, the response to medical or surgical treatment and the detection of recurrences. These diseases represent a high impact on the mortality and morbidity in our patients. Our main objective is to review the findings on PET-CT of the most common head and neck tumors with an emphasis on malignancy which are studied in our institution.

Non-FDG PET in the practice of oncology.

Fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) is utilized in more than 90% of cancers in staging, re-staging, assessing therapy response and during the follow-up. However, not all tumors show significant increase of metabolic activity on FDG-PET imaging. This is particularly true for prostate cancer, neuroendocrine tumors and hepatic tumors. In this review we have considered those already used for clinical applications such as 11C- and 18F-Choline, 11C-Methionine and 18F-FET, 18F-DOPA, 68Ga-DOTA-somatostatine analogues, 11C-Acetate and 18F-FLT. Choline presents a high affinity for malignant prostate tissue, even if low grade. Choline can be labeled with either 11C or 18F, the former being the preference due to lower urinary excretion and patients exposure. The latter is more useful for possible distribution to centers lacking in on-site cyclotron. Methionine is needed for protein synthesis and tumor cells require an external supply of methionine. These tracers have primarily been used for imaging of CNS neoplasms. The most appropriate indication is when conventional imaging procedures do not distinguish between edema, fibrosis or necrosis and disease relapse. In addition, the uptake of 11C-Methionine is proportional to the tumor grade and, therefore, the maximum small unilamellar vesicles (SUV) inside the brain mass before therapy is somehow considered a prognostic value. Neuroendocrine tumors (carcinoids, pheocromocytoma, neuroblastoma, medullary thyroid cancer, microcytoma, carotid glomus tumors, and melanoma) demonstrate an increased activity of L-DOPA decarboxylase, and hence they show a high uptake of 18FDOPA. For the study of NETs, 68Ga-DOTA-TOC/DOTA-NOC has been introduced as PET tracer. This compound for PET imaging has a high affinity for sst2 and sst5 and has been used in the detection of NETs in preliminary studies; 68Ga-DOTA-NOC PET is useful before metabolic radiotherapy in order to evaluate the biodistribution of the therapeutic compound; 18F-FLT is a specific marker of cell proliferation and the most important field of application of FLT is lung cancer. Other tracers are used in PET utilized as markers of hypoxia inside big neoplastic masses include 18F-MISO, 64Cu-ATSM, 18F-EF5, which highlight the presence of hypoxic areas are useful for patients that must be treated with radiotherapy.

Radiolabeled somatostatin analogs for radionuclide imaging and therapy in patients with gastroenteropancreatic neuroendocrine tumors.

Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are a rare type of cancer that can arise from the diffused endocrine system, located in the gastrointestinal (GI) tract (carcinoids) and in the pancreas (insular tumors). Approximately 2% of all malignant tumours of the gastrointestinal system are GEP-NETs which can express somatostatin receptors. 111In-pentetreotide (octreoscan) and 68Ga-DOTA NOC (68Ga-labelled [1,4,7,10- tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-Octreotide) are the commonly used radiopharmaceuticals for imaging. Once localized using 68Ga DOTA NOC or octreoscan, these tumours can be successfully targeted with radiolabelled somatostatin analogues. This review focuses on common nuclear medicine procedures used in both imaging and treatment of these tumors.

Radiolabeling of NOTA and DOTA with Positron Emitting 68Ga and Investigation of In Vitro Properties / 핵의학분자영상

PURPOSE: We established radiolabeling conditions of NOTA and DOTA with a generator-produced PET radionuclide 68Ga and studied in vitro characteristics such as stability, serum protein binding, octanol/water distribution, and interference with other metal ions. MATERIALS AND METHODS: Various concentrations of NOTA.3HCl and DOTA.4HCl were labeled with 1 mL 68GaCl3 (0.18~5.75 mCi in 0.1 M HCl) in various pH. NOTA.3HCl (0.373 mM) was labeled with 68GaCl3 (0.183~0.232 mCi/0.1 M HCl 1.0 mL) in the presense of CuCl2, FeCl2, InCl3, FeCl3, GaCl3, MgCl2 or CaCl2 (0~6.07 mM) at room temperature. The labeling efficiencies of 68Ga-NOTA and 68Ga-DOTA were checked by ITLC-SG using acetone or saline as mobile phase. Stabilities, protein bindings, and octanol distribution coefficients of the labeled compounds also were investigated. RESULTS: 68Ga-NOTA and 68Ga-DOTA were labeled optimally at pH 6.5 and pH 3.5, respectively, and the chelates were stable for 4 hr either in the reaction mixture at room temperature or in the human serum at 37 degreesC. NOTA was labeled at room temperature while DOTA required heating for labeling. 68Ga-NOTA labeling efficiency was reduced by CuCl2, FeCl2, InCl2, FeCl3 or GaCl3, however, was not influenced by MgCl2 or CaCl2. The protein binding was low (2.04~3.32%). Log P value of 68Ga-NOTA was -3.07 indicating high hydrophilicity. CONCLUSION: We found that NOTA is a better bifunctional chelating agent than DOTA for 68Ga labeling. Although, 68Ga-NOTA labeling is interfered by various metal ions, it shows high stability and low serum protein binding.