Small animal PET is a noninvasive molecular imaging technique, which provides an important bridge between experimental sciences and clinical sciences, and plays an unique role in medicine and drug development. Advantages and challenges, fundamentals, and development of small animal PET are reviewed and applications of small animal PET in medicine and drug development are discussed in this article.

OBJECTIVE　To determine the pharmacokinetic parameters of perlolyrine in rats.METHODS　The plasma concentration and pharmacokinetic parameters of perlolyrine were determined by means of GC-MS with selected ion (m/z 247 and m/z 248) and ［2-15N］perlolyrine(m/z 248) as the internal standard.RESULTS　The concentration-time profile of perlolyrine after oral administration of perlolyrine fitted a two-compartment open model.The pharmacokinetic parameters were t1/2α=0.31 h, t1/2β=4.62 h, t1/2ka=0.10 h, tmax=0.34 h, cmax=18.74 ng.mL-1,K12=0.82 h-1, K21=0.38h-1,K10=0.29 h-1,Vb=108.16 L.kg-1,AUC=98.54 ng.h.mL-1,respectively.CONCLUSION　The method is constant,sensitive and accurate.It provided a scientific basis for the clinical use of perlolyrine.

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.

Objective To synthesize 18F labeled N-(2-18 F-fluoropropionyl)-L-glutamine (18 F-FPGLN) for tumor PET imaging,and to perform its biodistribution study on normal mice and PC-3 tumorbearing nude mice.Methods 4-nitrophenyl-2-18F-fluoropropionate (18F-NFP) was synthesized on the MF2V-IT-I synthesizer and was purified by semi-preparative HPLC.Anhydrous 18F-NFP was added to a solution of L-glutanine t-butyl ester to synthesize 18F-FPGLN t-butyl ester,which was hydrolyzed by HCl (3 mol/L) and neutralized with NaOH (2 mol/L) solution.18F-FPGLN product was collected for further study.Biodistribution study was performed on normal Kunming mice and PC-3 prostate cancer tumor-bearing nude mice,respectively.Results 18F-FPGLN was synthesized with 10％-15％ (decay uncorrected) overall radiochemical yield after 130 min of radiosynthesis.The radiochemical purity was higher than 96％.Rapid and high uptake of radiotracer was observed within the kidneys,and was quickly excreted through the urinary bladder.The uptake in kidney reached (35.0±1.2) ％ID/g at 5 min post-injection,and descended to (1.5±0.3) ％ID/g at 120 min.The liver,lung,heart and small intestine showed relatively moderate uptake of radioactivity.The uptake in the pancreas,muscle,spleen,stomach and brain was low,and the lowest uptake of (1.5±0.3) ％ID/g was found in the brain at 30 min post injection.High accumulation of 18F-FPGLN in PC-3 xenograft was observed,and the tumor/muscle ratio reached 2.07 at 60 min post injection.Conclusion A novel N-position 18F-labeled glutamine analogs 18F-FPGLN,with favorable pharmacokinetic characteristics,is synthesized successfully,which makes it possible to perform tumor PET imaging using 18F-FPGLN subsequently.

OBJECTIVE: To study automated synthesis of 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) via on-column hydrolysis. METHODS: Automated synthesis of (18)F-FDG was performed by the on-column hydrolysis procedure in TRACERlab FXF-N synthesizer. (18)F-FDG injection was obtained via nucleophilic fluorination of 1, 3, 4, 6-tetra-O-acetyl-2-O-trifluoromethanesulfony-beta-D-mannopyranose as the precursor molecule with (18)F-fluoride, hydrolysis of the (18)F-labeled intermediate on SEP-PAK C18 cartridges with 2 mol/L NaOH solution, and purification and neutralization with SEP-PAK cartridges. RESULTS: The uncorrected radiochemical yield of (18)F-FDG was more than 60% within the total synthesis time shorter than 20 min. The radiochemical purity of (18)F-FDG was above 99%. CONCLUSION On-column hydrolysis is simple and practical for the automated synthesis of (18)F-FDG. (18)F-FDG injection produced by this procedure can be used in clinical PET imaging.
Adult ; Aged ; Automation ; methods ; Fluorodeoxyglucose F18 ; chemical synthesis ; Humans ; Hydrolysis ; Kidney Neoplasms ; diagnostic imaging ; Liver Neoplasms ; diagnostic imaging ; Male ; Positron-Emission Tomography ; Radiography ; Radiopharmaceuticals ; chemical synthesis

Objective To investigate the clinical value of [11C]CFT PET in the diagnosis and severity assessment of Parkinson disease (PD). Methods Thirty-eight patients with PD at various Hoehn & Yahr (H&Y) stages were included and underwent a [11C]CFT PET scan. The correlation between [11C]CFT uptake and unified Parkinson disease rating scale part III (UPDRS III) of PD patients was evaluated by calculating Pearson’s regression coefficient. Statistical parametric mapping (SPM) analysis was performed to compare the difference of dopamine transporter (DAT) distribution between ear-ly and advanced PD patients. Results There was a significant reduction of [11C]CFT uptake in the bilateral striatum of PD patients. There was a significant negative correlation between clinical scores of UPDRS III, rigidity, bradykinesia, pos-ture, gait and [11C]CFT uptake in the striatum. The SPM analysis revealed a significant and asymmetric decrease of [11C] CFT uptake in the striatum, predominantly on the putamen and caudate nucleus contralateral to the onset limb, in the posterior area of ipsilateral putamen in early PD (H&Y 1-2) patients compared with the normal controls. There was a sig-nificant symmetric decrease of [11C]CFT uptake in both putamen and caudate nucleus in advanced PD (H&Y 3-5) pa- tients, compared with normal controls. Compared with early PD patients, the reduction of DAT was more severe in bilater-al caudate nucleus and the ipsilateral putamen in the advanced PD patients. Conclusions [11C]CFT PET is a sensitive biomarker in the diagnosis and assessment of disease severity of PD patients.

Objective To investigate the clinical values of L-6-18 F-fluoro-3,4-dihydroxyphenylala-nine ( 18 F-DOPA) PET in the diagnosis and severity assessment of early-stage Parkinson's disease ( PD) . Methods Thirty-eight patients (24 males, 14 females; age:34-74 years) with early-stage PD (Hoehn-Yahr ( H-Y) staging:1-2) and 5 age-matched healthy volunteers ( all males;age:45-65 years) from July 2016 to March 2017 were included and underwent 18 F-DOPA PET scan in this retrospective study. The stria-tal-to-occipital ratio ( SOR) was calculated and compared between PD patients and healthy volunteers. The unified PD rating scale ( UPDRS) Ⅲ score and H-Y staging were used to evaluate the clinical symptoms. Two-sample t test and Pearson correlation analysis were used. Results In the control group, 18 F-DOPA SORs in bilateral putamen and caudate nucleus were 2.50±0.24 and 2.61±0.23, respectively. In PD group, the SORs of ipsilateral and contralateral putamen nucleus were 2.02±0.27 and 1.80±0.26 respectively, lower than those in the control group ( t values:-4.006,-5.440, both P<0.01) . The SORs of ipsilateral and contralater-al caudate nucleus were 2.16±0.32 and 2.08±0.28 respectively, lower than those in the control group ( t val-ues:-2.990,-4.047, both P<0.01). The SORs of contralateral putamen and caudate nucleus were signifi-cantly lower than those of the ipsilateral striatum respectively (t values:-6.431,-3.837, both P<0.01). Fur-thermore, the SORs in the striatum (putamen and caudate nucleus) were negatively correlated with UPDRSⅢscore, H-Y staging, and duration of disease (r values:from-0.526 to-0.369, all P<0.05). Conclusions 18F-DOPA PET can reflect the changes in the striatum neurons, and it may be an important method in the diag-nosis and assessment of early-stage PD patients.

Objective:To explore the relationship between 18F-fibroblast activation protein inhibitor (FAPI)-42 SUV max of primary gastric cancer and clinicopathological factors of patients. Methods:Fifty-one patients (31males, 20 females, age: 51(47, 65) years) with gastric cancer who underwent 18F-FAPI-42 PET/CT before surgical resection in Nanfang Hospital, Southern Medical University from February 2022 to January 2023 were analyzed retrospectively. The clinicopathological factors that might affect tumor SUV max (including gender, age, tumor location, pathological type, histological grade, Lauren classification, vascular and(or) neural invasion, programmed cell death-ligand 1 (PD-L1) expression, pathologic(p)T stage, pN stage and pTNM stage) were evaluated by the univariate analysis (Mann-Whitney U test or Kruskal-Wallis rank sum test) and multivariate analysis (multiple linear regression analysis). Results:The sensitivity of 18F-FAPI-42 PET/CT in the diagnosis of patients with primary gastric cancer was 82.35% (42/51). The diagnostic sensitivities for early gastric cancer (T1) and locally advanced gastric cancer (T2-T4) were 59.09%(13/22) and 100%(29/29), respectively. The SUV max of primary lesion was 4.90(1.71, 12.51). The univariate analysis showed that SUV max of primary gastric cancer was related to tumor location ( z=-2.00, P=0.046), pT stage ( H=36.94, P<0.001), pN stage ( z=-3.89, P<0.001), pTNM stage ( H=31.49, P<0.001) and vascular and(or) nerve invasion ( z=-5.22, P<0.001), but not related to pathological type, histological grade, Lauren typing, and PD-L1 expression ( z values: from -1.78 to -0.09, all P>0.05). pT stage was found to be a significant independent factor for SUV max in primary gastric lesion by multivariate analysis ( t=2.52, P=0.015). Conclusions:The 18F-FAPI-42 SUV max of primary tumor was related to tumor location, pT stage, pN stage, pTNM stage, and vascular and(or) nerve invasion; pT stage is an independent factor affecting tumor SUV max. The ability of 18F-FAPI-42 PET/CT to detect gastric cancer is mainly affected by pT stage.

In recent years, fibroblast activation protein (FAP) has emerged as an attractive target for the diagnosis and radiotherapy of cancers using FAP-specific radioligands. Herein, we aimed to design a novel ¹⁸F-labeled FAP tracer ([¹⁸F]AlF-P-FAPI) for FAP imaging and evaluated its potential for clinical application. The [¹⁸F]AlF-P-FAPI novel tracer was prepared in an automated manner within 42 min with a non-decay corrected radiochemical yield of 32 ± 6% (n = 8). Among A549-FAP cells, [¹⁸F]AlF-P-FAPI demonstrated specific uptake, rapid internalization, and low cellular efflux. Compared to the patent tracer [¹⁸F]FAPI-42, [¹⁸F]AlF-P-FAPI exhibited lower levels of cellular efflux in the A549-FAP cells and higher stability in vivo. Micro-PET imaging in the A549-FAP tumor model indicated higher specific tumor uptake of [¹⁸F]AlF-P-FAPI (7.0 ± 1.0% ID/g) compared to patent tracers [¹⁸F]FAPI-42 (3.2 ± 0.6% ID/g) and [⁶⁸Ga]Ga-FAPI-04 (2.7 ± 0.5% ID/g). Furthermore, in an initial diagnostic application in a patient with nasopharyngeal cancer, [¹⁸F]AlF-P-FAPI and [¹⁸F]FDG PET/CT showed comparable results for both primary tumors and lymph node metastases. These results suggest that [¹⁸F]AlF-P-FAPI can be conveniently prepared, with promising characteristics in the preclinical evaluation. The feasibility of FAP imaging was demonstrated using PET studies.