Intraindividual comparison of <Superscript>68</Superscript>Ga-DOTA-TATE and <Superscript>18</Superscript>F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours

Aim  To compare the diagnostic impact of ⁶⁸Ga-DOTA-TATE and ¹⁸F-DOPA PET in the diagnosis of well-differentiated metastatic neuroendocrine tumours (NET). Methods  PET/CT using both ⁶⁸Ga-DOTA-TATE and ¹⁸F-DOPA was performed in 25 patients with histologically proven metastatic NET (nine gut, five pancreas, six lung, one paranasal sinus, four with unknown primary). Analyses of PET examinations were patient-based (pathological uptake: yes/no), and based on tumour regions (primary tumour if present and metastases of liver, lung, bones and lymph nodes). The results were compared with the results of contrast enhanced CT, and with plasma serotonin levels, which were available in 24 of the 25 patients. Results  Patient-based sensitivities were 96% for ⁶⁸Ga-DOTA-TATE PET and 56% for ¹⁸F-DOPA PET. ⁶⁸Ga-DOTA-TATE PET delineated metastases in 54 of 55 positive metastatic tumour regions in contrast to 29 of 55 delineated by ¹⁸F-DOPA PET. Overall, ⁶⁸Ga-DOTA-TATE was superior to ¹⁸F-DOPA in 13 patients (two patients showed fewer positive tumour regions with ¹⁸F-DOPA PET). The results were comparable in 12 patients. In 13 of 24 patients, plasma serotonin levels were elevated, and 11 of these 13 patients showed pathological uptake of ¹⁸F-DOPA. Of the 11 patients with normal levels of serotonin, 3 also showed positive ¹⁸F-DOPA uptake. In patients positive for ¹⁸F-DOPA uptake the maximum tumour SUVs were correlated with the levels of serotonin (r=0.66, p=0.01). Conclusion  In this study ⁶⁸Ga-DOTA-TATE PET proved clearly superior to ¹⁸F-DOPA PET for detection and staging of NET. ¹⁸F-DOPA uptake tended to be increased in those patients with elevated plasma serotonin. We conclude that ¹⁸F-DOPA PET should be employed in patients with NET with negative ⁶⁸Ga-DOTA-TATE PET and elevated plasma serotonin.     

肝胆肿瘤患者68Ga-FAPI-04 PET显像的内照射剂量及分布研究

目的 评估⁶⁸Ga-FAPI-04 PET/CT检查在肝胆肿瘤患者中的内照射剂量及生物分布。方法 本研究纳入因肝脏占位于北京协和医院接受PET/CT检查的6例患者,经静脉注射⁶⁸Ga-FAPI-04（170.57 ±14.43） MBq后分别于第3、10、15、20、30和60 min进行全身显像。观察显像剂的生物分布;手动勾画感兴趣区;所有靶器官的内照射剂量应用OLINDA/EXM软件计算。结果 ⁶⁸Ga-FAPI-04在肝脏内放射性本底消退较快,在肿瘤组织内放射性摄取较为稳定,病灶平均SUV_max在注射后20 min达到最大（13.87 ±2.55）;病灶平均靶本比逐渐升高,在注射后30 min达到最大（10.09 ±8.17）。1次⁶⁸Ga-FAPI-04 PET/CT扫描的全身有效剂量为（0.020 ±0.002） mSv/MBq,吸收剂量最高的器官是膀胱壁,为（0.146 ±0.035） mSv/MBq。结论 ⁶⁸Ga-FAPI-04与¹⁸F-FDG全身有效剂量相近;肿瘤摄取快速,肝脏背景低,且不受血糖水平影响,有望成为潜在的肝胆肿瘤PET/CT显像药物。     

<Superscript>68</Superscript>Ga-labelled DOTA-derivatised peptide ligands

⁶⁸Ge/⁶⁸Ga generators provide cyclotron-independent access to positron emission tomography (PET) radiopharmaceuticals. We describe a system which allows the safe and efficient handling of ⁶⁸Ge/⁶⁸Ga generator eluates for labelling of DOTA-derivatised peptide ligands. The system comprises concentration and purification of the ⁶⁸Ga eluate as well as labelling and purification steps for peptides, and can be used with different ⁶⁸Ge/⁶⁸Ga generator types. The suitability and efficiency were tested with two different DOTA-derivatised somatostatin derivatives and a DOTA-derivatised bombesin derivative. Amounts of 10–20 nmol of the peptides were sufficient and resulted in labelling yields of 50% for all peptides. The built-in safety precautions have proven to be appropriate in allowing use of the method for routine clinical applications. The system was set up and operated in a hot lab by personnel with no previous experience in the preparation of PET radiopharmaceuticals.     

Comparison between <Superscript>68</Superscript>Ga-DOTA-NOC and <Superscript>18</Superscript>F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours

PURPOSE: (18)F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that (18)F-DOPA and (68)Ga-DOTA-NOC are more accurate for disease assessment and (68)Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. AIM: The aim of this study was to compare (68)Ga-DOTA-NOC and (18)F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. MATERIALS AND METHODS: Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for (18)F-DOPA and (68)Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). RESULTS: The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. (68)Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while (18)F-DOPA PET was positive in 9/13. On a lesions basis, (68)Ga-DOTA-NOC identified more lesions than (18)F-DOPA (71 vs 45), especially at liver, lung and lymph node level. (68)Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while (18)F-DOPA identified the primary only in two of eight cases. CONCLUSIONS: Although the patients studied are few and heterogeneous, our data show that (68)Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over (18)F-DOPA.     

Correlation of immunohistopathological expression of somatostatin receptor 2 with standardised uptake values in <Superscript>68</Superscript>Ga-DOTATOC PET/CT

Purpose  In clinical routine somatostatin analogue positron emission tomography/computed tomography (PET/CT) such as ⁶⁸Ga-DOTA-Tyr-octreotide (DOTATOC)-PET/CT could substitute conventional ¹¹¹In-Octreotide scintigraphy. Immunohistochemistry (IHC) for somatostatin receptor 2 (SSTR2) might be a tool to predict positivity of ⁶⁸Ga-DOTATOC in patients where initial staging was not performed, e.g., in incidental findings. We therefore compared a score of SSTR2-IHC with the in vivo standard uptake value (SUV) of preoperative or prebiopsy ⁶⁸Ga-DOTATOC PET/CT. Materials and methods  In 18 patients, ⁶⁸Ga-DOTATOC PET/CT scans were quantified with SUV calculations and correlated to a cell membrane-based SSTR2-IHC score (ranging from 0 to 3). Results  Negative IHC scores were consistent with SUV values below 10. Furthermore, all score 2 and 3 specimens corresponded with high SUV values (above 15). Conclusion  SSTR2-IHC scores correlated well with SUV values and we propose to use SSTR2 immunohistochemistry in patients missing a preoperative PET scan to indicate ⁶⁸Ga-DOTATOC-PET/CT as method for restaging and follow-up in individual patients.     

Concordance between results of somatostatin receptor scintigraphy with <Superscript>111</Superscript>In-DOTA-DPhe<Superscript>1</Superscript>-Tyr<Superscript>3</Superscript>-octreotide and chromogranin A assay in patients with neuroendocrine tumours

Purpose  Somatostatin receptor scintigraphy (SRS) and chromogranin A (CgA) assay have successfully been implemented in the clinical work-up and management of neuroendocrine tumour (NET) patients. However, there is still a lack of studies comparing results in these patients. Our aim was to compare directly in NET patients SRS and CgA assay results with special regard to tumour features such as grade of malignancy, primary origin, disease extent and function. Methods  One hundred twenty consecutive patients with histological confirmed NETs were investigated with ¹¹¹In-DOTA-DPhe¹-Tyr³-octreotide (¹¹¹In-DOTA-TOC) SRS and CgA immunoradiometric assay. Tumours were classified by cell characteristics [well-differentiated NETs, well-differentiated neuroendocrine carcinomas, poorly differentiated neuroendocrine carcinomas (PDNECs)], primary origin (foregut, midgut, hindgut, undetermined), disease extent (limited disease, metastases, primary tumour and metastases) and functionality (secretory, nonsecretory). Results  SRS was positive in 107 (89%) patients; CgA levels were increased in 95 (79%) patients. Overall, concordance between SRS and CgA results was found in 84 patients. Positive SRS but normal CgA level were found in 24 patients, with higher prevalence (p < 0.05) in patients with nonsecretory tumours. Conversely, negative SRS but CgA level increased were seen in 12 patients, with higher proportion (p < 0.05) in patients with PDNECs and tumours of hindgut origin. Conclusions  Overall, ¹¹¹In-DOTA-TOC SRS proved to be more sensitive than CgA in NETs patients. Tumour differentiation, disease extent and presence of liver metastases impact both SRS and CgA results, whereas nonsecretory activity is a negative predictor of only CgA increase. PDNECs and hindgut origin of tumours predispose to discrepancies with negative SRS but increased CgA levels.     

Prospective dosimetry with <Superscript>99m</Superscript>Tc-MDP in metabolic radiotherapy of bone metastases with <Superscript>153</Superscript>Sm-EDTMP

Purpose

On the basis of the encouraging results achieved in several clinical trials and its proven therapeutic efficacy, ¹⁵³Sm-ethylene diamine tetramethylene phosphonic acid (EDTMP) has become widely used to palliate pain from bone metastases. The results reported in the literature have led the product suppliers (QUADRAMET®, Schering) to suggest administering a fixed activity per kilogram (37 MBq/kg). However, considering the observed extreme inter-patient variability of skeletal uptake of ¹⁵³Sm-EDTMP, a real therapy optimization would require the individualization of the activity to be administered on a dosimetric basis. This should be planned taking into account the generally accepted 2-Gy dose constraint to the haematopoietic red marrow, the critical organ in palliative treatments with beta-emitting, bone-seeking radiopharmaceuticals.

Methods

Seven to 14 days before treatment with ¹⁵³Sm-EDTMP, 44 patients underwent ^99mTc-methylene diphosphonate (MDP) total-body bone scan with two scans (the first within 10 min of injection, the second after 6 h). The percentage bone uptake (Tc_%) was evaluated as the ratio between total counts at 6 h, adjusted for decay, and total counts at the first scan. Tc_% was then compared to Sm_% similarly derived from 10-min and 24-h whole-body scans. Tc_% and Sm_% were compared both with and without Brenner’s method for soft tissue uptake.

Results

The correlation between Tc_% and Sm_% was R ²?=?0.81 and R ²?=?0.88 with and without soft tissue correction, respectively. The difference between their average values was statistically significant (Sm_%?=?64.3?±?15.2, Tc_%?=?56.2?±?16.0; p?=?0.017) with soft tissue correction, while was not statistically significant (Sm_%?=?68.2?±?15.5, Tc_%?=?66.9?±?14.0; p?=?0.670) without soft tissue correction.

Conclusions

The rate of retention of ^99mTc-MDP in bone provides a reliable estimate of the ¹⁵³Sm-EDTMP rate of retention. The proposed method can be usefully adopted for prospective dosimetry seeing its extreme simplicity, and it requires no special investment in terms of human or instrumental resources. This allows an optimization of administered ¹⁵³Sm-EDTMP activity.

     

<Superscript>11</Superscript>C-acetate PET imaging of lung cancer: comparison with <Superscript>18</Superscript>F-FDG PET and <Superscript>99m</Superscript>Tc-MIBI SPET

Recently carbon-11 acetate (AC) positron emission tomography (PET) has been reported to be of clinical value for the diagnosis of cancer that is negative on fluorine-18 fluorodeoxyglucoce (FDG) PET. We investigated the uptake of AC in lung cancer to determine whether this tracer is of potential value for tumour detection and characterisation, and to compare AC PET imaging with FDG PET and technetium-99m sestamibi (MIBI) single-photon emission tomography (SPET). Twenty-three patients with 25 lung cancers underwent AC and FDG PET. Twenty of 23 patients were also investigated with MIBI SPET. Dynamic images were acquired for 26 min after the injection of 555 MBq of AC. Standardised uptake values (SUVs) and/or tumour to non-tumour activity ratios (T/N) for each tumour were investigated at 10–20 min after AC administration, 40–60 min after administration of 185 MBq FDG and 15–45 min after administration of 555 MBq MIBI. Twenty lung cancers were resected surgically, and the degree of tracer uptake in the primary lesion was correlated with histopathological features (cell dedifferentiation and aggressiveness) and prognosis. Rapid uptake of AC followed by extremely slow clearance was observed. For the purpose of tumour identification, AC PET was inferior to FDG PET in 8 of 25 (32%) lung cancers, and the T/N of AC was lower than that of FDG. However, AC PET was superior to FDG PET in the identification of a slow-growing tumour (bronchiolo-alveolar carcinoma). There was a positive correlation between AC uptake (T/N) and MIBI uptake (T/N) (r=0.799, P<0.0001). A positive correlation was not observed between either AC or MIBI uptake and the degree of cell dedifferentiation in lung adenocarcinomas, whereas FDG uptake did correlate with the degree of cell dedifferentiation. In lung adenocarcinoma, there was a weak correlation between aggressiveness and FDG uptake, but no correlation was evident for AC and MIBI. In addition, a positive correlation was not observed between AC or MIBI uptake and postoperative recurrence in lung adenocarcinoma, whereas FDG uptake did correlate with postoperative recurrence. Thus, the greater the FDG uptake, the higher the malignant grade. In conclusion, for the purpose of tumour identification, AC PET was inferior to FDG PET but superior to MIBI SPET. Neither AC nor MIBI uptake reflects the malignant grade in lung adenocarcinoma, whereas FDG uptake does. AC PET is less diagnostically informative than FDG PET in patients with lung cancer. However, AC PET may play a complementary role in the identification of low-grade malignancies that are not FDG avid.     

Von Hippel-Lindau Syndrome: Demonstration of Entire Disease Spectrum with 68Ga-DOTANOC PET-CT

Von Hippel-Lindau (VHL) syndrome is a rare neoplastic disorder characterized by central nervous system (CNS) and visceral tumors. We here present ⁶⁸Ga-labelled [1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-Nal3-Octreotide positron emission tomography computed tomography findings in a 52 year old female with VHL syndrome, demonstrating both CNS and visceral tumors.     

<Superscript>68</Superscript>Ga-DOTAVAP-P1 PET imaging capable of demonstrating the phase of inflammation in healing bones and the progress of infection in osteomyelitic bones

Purpose Differentiation between bacterial infection and nonbacterial inflammation remains a diagnostic challenge. Vascular adhesion protein 1 (VAP-1) is a human endothelial protein whose cell surface expression is induced under inflammatory conditions, thus making it a highly promising target molecule for studying inflammatory processes in vivo. We hypothesized that positron emission tomography (PET) with gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N′,N″,N′′′,N″″-tetraacetic acid-peptide targeted to VAP-1 (⁶⁸Ga-DOTAVAP-P1) could be feasible for imaging the early inflammatory and infectious processes in healing bones. Materials and methods Thirty-four Sprague–Dawley rats with diffuse Staphylococcus aureus tibial osteomyelitis and 34 rats with healing cortical bone defects (representing the inflammation stage of healing) were PET imaged using ⁶⁸Ga-DOTAVAP-P1 as a tracer. In addition, peripheral quantitative computed tomography and conventional radiography were performed. Bone samples for quantitative bacteriology and specimens were also processed for histomorphometry of inflammatory and infectious reactions. Results PET imaging showed an uptake of ⁶⁸Ga-DOTAVAP-P1 in both the osteomyelitic bones and the healing cortical bone defects during the first 36 h after surgery. Thereafter, only the osteomyelitic tibias were delineated by PET. The osteomyelitic and control animals showed a similar uptake of the ⁶⁸Ga-DOTAVAP-P1 at 24 h, whereas a significant difference was observed at 7 days (p < 0.0001). Conclusions The current study showed that PET imaging with the new ⁶⁸Ga-DOTAVAP-P1 is capable of accurately demonstrating the phase of inflammation in healing bones and the progress of bacterial infection in osteomyelitic bones. Consequently, this novel imaging agent allowed for the differentiation of bone infection due to S. aureus and normal bone healing as soon as 7 days after onset.     

Metastatic Neuroendocrine Tumour in a Renal Transplant Recipient: Dual-Tracer PET-CT with 18F-FDG and 68Ga-DOTANOC in This Rare Setting

Nuclear Medicine and Molecular Imaging - Recipients of renal transplant are at increased risk of developing various malignancies, especially post-transplant lymphoproliferative disorder (PTLD) and...     

Tetrafluorophenolate of HBED-CC: a versatile conjugation agent for <Superscript>68</Superscript>Ga-labeled small recombinant antibodies

Purpose  The success of ⁶⁸Ga-labeled peptides for positron emission tomography of neuroendocrine tumors is mainly depending on the complex chemistry of this radioisotope. 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), the chelator of choice has however limitations if its application is expanded to heat-sensitive proteins. Recombinant antibodies like single chain Fv or diabodies belong to this class of proteins. They are suited to provide imaging contrast despite the short-lived ⁶⁸Ga because of their rapid blood clearances and nanomolar affinities. The heterobifunctional agent N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid (HBED-CC) was chosen as an alternative ligand because this agent is complexing [⁶⁸Ga]Ga³⁺ much faster than DOTA at ambient temperatures. Materials and methods  A versatile technology for HBED-CC conjugation of proteins and ⁶⁸Ga-labeling has been developed. This included HBED-CC–tetrafluorophenol (TFP) ester synthesis, coupling to the antibody at various pH and complexation reactions performed in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer under different conditions. Results  The synthesis of the monoreactive 2,3,5,6-tetrafluorophenolate of HBED-CC at a carboxyl group not participating in complex formation used [Fe(HBED-CC)]⁻ for ester formation. The removal of Fe³⁺ from purified (HBED-CC)TFP ester was achieved with RP₁₈ cartridge technology. The conjugation chemistry was performed with mAb425 which binds to the epidermal growth factor receptor (EGFR). This protein was used for optimizing purposes only. The influence of complexation parameters like temperature, pH, reaction time, and HBED-CC/antibody ratio on the biological activity of this model antibody was investigated. Furthermore, the outcome of this labeling procedure on the biological activity of a recombinant diabody (50 kDa) was studied. Conclusion  It is known that small HBED-CC/antibody ratios are prerequisites for minimal interference of labels with antigen-binding domains. Here, the coupling of about one HBED-CC per antibody proved to be sufficient for efficient ⁶⁸Ga labeling, pointing to the successful application of ⁶⁸Ga for molecular imaging with small recombinant proteins.     

Radiation dosimetry of <Emphasis Type="Italic">N</Emphasis>-([<Superscript>11</Superscript>C]methyl)benperidol as determined by whole-body PET imaging of primates

Purpose N-([¹¹C]methyl)benperidol ([¹¹C]NMB) can be used for positron emission tomography (PET) measurements of D₂-like dopamine receptor binding in vivo. We report the absorbed radiation dosimetry of i.v.-administered ¹¹C-NMB, a critical step before applying this radioligand to imaging studies in humans. Materials and methods Whole-body PET imaging with a CTI/Siemens ECAT 953B scanner was done in a male and a female baboon. After i.v. injection of 444–1221 MBq of ¹¹C-NMB, sequential images taken from the head to the pelvis were collected for 3 h. Volumes of interest (VOIs) were identified that entirely encompassed small organs (whole brain, striatum, eyes, and myocardium). Large organs (liver, lungs, kidneys, lower large intestine, and urinary bladder) were sampled by drawing representative regions within the organ volume. Time–activity curves for each VOI were extracted from the PET, and organ residence times were calculated by analytical integration of a multi-exponential fit of the time–activity curves. Human radiation doses were estimated using OLINDA/EXM 1.0 and the standard human model. Results Highest retention was observed in the blood and liver, each with total residence times of 1.5 min. The highest absorbed radiation doses were to the heart (10.5 mGy/kBq) and kidney (9.19 mGy/kBq), making these the critical organs for [¹¹C]NMB. A heart absorption of 50 mGy would result from an injected dose of 4,762 MBq [¹¹C]NMB. Conclusions Thus, this study suggests that up to 4,762 MBq of [¹¹C]NMB can be safely administered to human subjects for PET studies. Total body dose and effective dose for [¹¹C]NMB are 2.82 mGy/kBq and 3.7 mSv/kBq, respectively.     

<Superscript>68</Superscript>Ga-labeled NOTA-RGD-BBN peptide for dual integrin and GRPR-targeted tumor imaging

Purpose  Radiolabeled Arg-Gly-Asp (RGD) and bombesin (BBN) peptide analogs have been extensively investigated for the imaging of tumor integrin α_vβ₃ and gastrin-releasing peptide receptor (GRPR) expression, respectively. Recently, we designed and synthesized a RGD-BBN heterodimeric peptide from c(RGDyK) and BBN(7–14) through a glutamate linker. The goal of this study was to investigate the dual receptor-targeting property and tumor diagnostic value of RGD-BBN heterodimeric peptide labeled with generator-eluted ⁶⁸Ga (t_1/2 68 min, β⁺ 89% and EC 11%), ⁶⁸Ga-NOTA-RGD-BBN. Methods  RGD-BBN heterodimer was conjugated with 1,4,7-triazacyclononanetriacetic acid (NOTA) and labeled with ⁶⁸Ga. The dual receptor binding affinity was investigated by a radioligand competition binding assay. The in vitro and in vivo dual receptor targeting of ⁶⁸Ga-NOTA-RGD-BBN was evaluated and compared with that of ⁶⁸Ga-NOTA-RGD and ⁶⁸Ga-NOTA-BBN. Results  NOTA-RGD-BBN had integrin α_vβ₃ and GRPR binding affinities comparable to those of the monomeric RGD and BBN, respectively. The dual receptor targeting property of ⁶⁸Ga-NOTA-RGD-BBN was validated by blocking studies in a PC-3 tumor model. ⁶⁸Ga-NOTA-RGD-BBN showed higher tumor uptake than ⁶⁸Ga-NOTA-RGD and ⁶⁸Ga-NOTA-BBN. ⁶⁸Ga-NOTA-RGD-BBN can also image tumors with either integrin or GRPR expression. Conclusion   ⁶⁸Ga-NOTA-RGD-BBN exhibited dual receptor targeting properties both in vitro and in vivo. The favorable characterizations of ⁶⁸Ga-NOTA-RGD-BBN such as convenient synthesis, high specific activity, and high tumor uptake, warrant its further investigation for clinical cancer imaging. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

<Superscript>11</Superscript>C-methionine uptake in cerebrovascular disease: A comparison with<Superscript>18</Superscript>F-FDG PET and<Superscript>99m</Superscript>Tc-HMPAO SPECT

OBJECTIVES: Carbon-11-L-methyl-methionine (11C-methionine) has been reported to be useful for evaluating brain tumors, but several other brain disorders have also shown signs of high methionine uptake. We retrospectively evaluated the significance of 11C-methionine uptake in cerebrovascular diseases, and also compared our results with those for 18F-FDG PET and 99mTc-HMPAO SPECT. METHODS: Seven patients, including 3 patients with a cerebral hematoma and 4 patients with a cerebral infarction, were examined. All 7 patients underwent both 11C-methionine PET and 99mTc-HMPAO SPECT, and 6 of them underwent 18F-FDG PET. RESULTS: A high 11C-methionine uptake was observed in all 3 patients with cerebral hematoma. Increased 99mTc-HMPAO uptake was observed in 2 out of 3 patients, and all 3 patients had decreased 18F-FDG uptake. Of 4 patients with a cerebral infarction, high 11C-methionine uptake was observed in 3. Increased 99mTc-HMPAO uptake was also observed in one patient, whereas 3 patients had decreased 18F-FDG uptake. CONCLUSIONS: We should keep in mind that high 11C-methionine uptake is frequently observed in cerebrovascular diseases. CVD should therefore be included in the differential diagnosis when encounting patients with a high 11C-methionine uptake.     

Detection of gastric cancer using <Superscript>18</Superscript>F-FLT PET: comparison with <Superscript>18</Superscript>F-FDG PET

Purpose  We prospectively investigated the feasibility of 3′-deoxy-3′-¹⁸F-fluorothymidine (FLT) positron emission tomography (PET) for the detection of gastric cancer, in comparison with 2-deoxy-2-¹⁸F-fluoro-d-glucose (FDG) PET, and determined the degree of correlation between the two radiotracers and proliferative activity as indicated by Ki-67 index. Methods  A total of 21 patients with newly diagnosed advanced gastric cancer were examined with FLT PET and FDG PET. Tumour lesions were identified as areas of focally increased uptake, exceeding that of surrounding normal tissue. For semiquantitative analysis, the maximal standardized uptake value (SUV) was calculated. Results  For detection of advanced gastric cancer, the sensitivities of FLT PET and FDG PET were 95.2% and 95.0%, respectively. The mean (±SD) SUV for FLT (7.0 ± 3.3) was significantly lower than that for FDG (9.4 ± 6.3 p < 0.05). The mean FLT SUV and FDG SUV in nonintestinal tumours were higher than in intestinal tumours, although the difference was not statistically significant. The mean (±SD) FLT SUV in poorly differentiated tumours (8.5 ± 3.5) was significantly higher than that in well and moderately differentiated tumours (5.3 ± 2.1; p < 0.04). The mean FDG SUV in poorly differentiated tumours was higher than in well and moderately differentiated tumours, although the difference was not statistically significant. There was no significant correlation between Ki-67 index and either FLT SUV or FDG SUV. Conclusion  FLT PET showed as high a sensitivity as FDG PET for the detection of gastric cancer, although uptake of FLT in gastric cancer was significantly lower than that of FDG.     

The clinical efficacy of <Superscript>18</Superscript>F-FDG-PET/CT in benign and malignant musculoskeletal tumors

Objective  Most of the current clinical data on the role of 2-[¹⁸F]fluoro-2-deoxy-d-glucose positron emission tomography (¹⁸F-FDG-PET) in musculoskeletal tumors come from patients studied with PET and less frequently with hardware fusion PET/computed tomography (CT). And the number of cases in each report is too small to clarify the exact clinical efficacy of PET or PET/CT. This prompted us to analyze our experience with ¹⁸F-FDG-PET/CT in a relatively large group of patients with musculoskeletal tumors. Methods   ¹⁸F-FDG-PET/CT was performed on 91 patients from May 2004 to June 2007. The final diagnosis was obtained from surgical biopsy in 83 patients (91%) and clinical follow-up in 8 (9%). We analyzed the characteristics and amount of ¹⁸F-FDG uptake in soft tissue and bone tumors, and investigated the ability of ¹⁸F-FDG-PET/CT to differentiate malignant from benign tumors. The cutoff maximum standardized uptake value (SUV_max) was calculated using the receiver-operation characteristic curve method. Sensitivity, specificity, and diagnostic accuracy were calculated with cutoff SUV_max and the final diagnosis. Unpaired t test was used for the statistical analysis. Results  Final diagnosis revealed 19 benign soft tissue tumors (mean SUV_max 4.7), 27 benign bone tumors (5.1), 25 malignant soft tissue tumors (8.8), and 20 malignant bone tumors (10.8). There was a significant difference in SUV_max between benign and malignant musculoskeletal tumors in total (P < 0.002), soft tissue tumors (P < 0.05), and bone tumors (P < 0.02). Sensitivity, specificity, and diagnostic accuracy were 80%, 65.2%, and 73% in total with cutoff SUV_max 3.8, 80%, 68.4%, and 75% in the soft tissue tumors with cutoff SUV_max 3.8, and 80%, 63%, and 70% in the bone tumors with cutoff SUV_max 3.7. Conclusions   ¹⁸F-FDG-PET/CT reliably differentiated malignant soft tissue and bone tumors from benign ones, although there were many false-positive and falsenegative lesions. Further studies with all kinds of musculoskeletal tumors in large numbers are needed to improve the diagnostic accuracy of ¹⁸F-FDG-PET/CT.     

Correlation of <Superscript>18</Superscript>F-FLT and <Superscript>18</Superscript>F-FDG uptake on PET with Ki-67 immunohistochemistry in non-small cell lung cancer

Purpose The nucleoside analogue 3′-deoxy-3′-¹⁸F-fluorothymidine (FLT) has recently been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively evaluated whether FLT uptake reflects proliferative activity as indicated by the Ki-67 index in non-small cell lung cancer (NSCLC), in comparison with 2-deoxy-2-¹⁸F-fluoro-D-glucose (FDG). Methods A total of 18 patients with newly diagnosed NSCLC were examined with both FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. Tumour lesions were identified as areas of focally increased uptake, exceeding background uptake in the lungs. For semi-quantitative analysis, the maximum standardised uptake value (SUV) was calculated. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens. Immunohistochemical findings were correlated with SUVs. Results The sensitivity of FLT and FDG PET for the detection of lung cancer was 72% and 89%, respectively. Four of the five false-negative FLT PET findings occurred in bronchiolo-alveolar carcinoma. The mean FLT SUV was significantly lower than the mean FDG SUV. A significant correlation was observed between FLT SUV and Ki-67 index (r = 0.77; p < 0.0002) and for FDG SUV (r = 0.81; p < 0.0001). Conclusion The results of this preliminary study suggest that, compared with FDG, FLT may be less sensitive for primary staging in patients with NSCLC. Although FLT uptake correlated significantly with proliferative activity in NSCLC, the correlation was not better than that for FDG uptake.     

Comparison of <Superscript>68</Superscript>Ga-DOTATOC PET and <Superscript>111</Superscript>In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours

Purpose Neuroendocrine tumours (NETs) can be imaged with scintigraphy using radiolabelled somatostatin analogues. The aim of our study was to compare the value of ⁶⁸Ga-DOTATOC PET and ¹¹¹In-DTPAOC SPECT (Octreoscan) in the detection of NET manifestations. Methods Twenty-seven NET patients were prospectively examined. ⁶⁸Ga-DOTATOC PET and ¹¹¹In-DTPAOC SPECT were performed using standard techniques. Treatment was not applied in between. Mean and maximum standardised uptake values (SUVs) were calculated for PET findings. Tumour/non-tumour ratios were calculated for SPECT findings. Findings were compared by a region-by-region analysis and verified with histopathology, CT and MRI within 21 days. Results SUVs of positive lesions on ⁶⁸Ga-DOTATOC PET ranged from 0.7 to 29.3 (mean SUV) and from 0.9 to 34.4 (maximum SUV). Tumour/non-tumour ratios on ¹¹¹In-DTPAOC SPECT ranged from 1.8 to 7.3. In imaging lung and skeletal manifestations, ⁶⁸Ga-DOTATOC PET was more efficient than ¹¹¹In-DTPAOC SPECT. All discrepant lung findings and 77.8% of discrepant osseous findings were verified as true positive PET interpretations. In regional comparison of liver and brain, ⁶⁸Ga-DOTATOC PET and ¹¹¹In-DTPAOC SPECT were identical. In lymph nodes, the pancreas and the gastro-intestinal system, different values of the two techniques were not indicated in regional analyses. In a single patient, surgical interventions were changed on the basis of ⁶⁸Ga-DOTATOC PET findings. Conclusion ⁶⁸Ga-DOTATOC PET is superior to ¹¹¹In-DTPAOC SPECT in the detection of NET manifestations in the lung and skeleton and similar for the detection of NET manifestations in the liver and brain. ⁶⁸Ga-DOTATOC PET is advantageous in guiding the clinical management. M. Henze and S. Engelbrecht contributed equally to this paper.     

Effects of anesthetic agents on cellular <Superscript>123</Superscript>I-MIBG transport and in vivo <Superscript>123</Superscript>I-MIBG biodistribution

Objectives Small animal imaging with meta-iodobenzylguanidine (MIBG) allows characterization of animal models, optimization of tumor treatment strategies, and monitoring of gene expression. Anesthetic agents, however, can affect norepinephrine (NE) transport and systemic sympathetic activity. We thus elucidated the effects of anesthetic agents on MIBG transport and biodistribution. Methods SK-N-SH neuroblastoma and PC-12 pheochromocytoma cells were measured for ¹²³I-MIBG uptake after treatment with ketamine (Ke), xylazine (Xy), Ke/Xy, or pentobarbital (Pb). NE transporters were assessed by Western blots. Normal ICR mice and PC-12 tumor-bearing mice were injected with ¹²³I-MIBG 10 min after anesthesia with Ke/Xy, Ke, Xy, or Pb. Plasma NE levels and MIBG biodistribution were assessed. Results Cellular ¹²³I-MIBG uptake was dose-dependently inhibited by Ke and Xy but not by Pb. Treatment for 2 h with 300 μM Ke, Xy, and Ke/Xy decreased uptake to 46.0 ± 1.6, 24.8 ± 1.5, and 18.3 ± 1.6% of controls. This effect was completely reversed by fresh media, and there was no change in NE transporter levels. In contrast, mice anesthetized with Ke/Xy showed no decrease of MIBG uptake in target organs. Instead, uptakes and organ-to-blood ratios were increased in the heart, lung, liver, and adrenals. Plasma NE was notably reduced in the animals with corresponding decreases in blood MIBG, which partly contributed to the increase in target organ uptake. Conclusion In spite of their inhibitory effect at the transporter level, Ke/Xy anesthesia is a satisfactory method for MIBG imaging that allows favorable target tissue uptake and contrast by reducing circulating NE and MIBG. Bong-Ho Ko and Jin-Young Paik equally contributed to this work. This work was supported by the Korea Research Foundation Grant KRF-2005-202-E00116. Presented in part at the fifth Annual Meeting of the Society for Molecular Imaging, Hawaii, August 30–September 2, 2006.