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Objective:To investigate the application of different imaging methods of 99Tc m-pyrophosphate (PYP) in the diagnosis and pathological classification of cardiac amyloidosis (CA). Methods:A total of 31 patients (22 males, 9 females, age 21-81(57.2±13.4) years) with suspected CA who underwent 99Tc m-PYP dual-phase scintigraphy (early-phase: 1 h, delay-phase: 2-3 h) and SPECT/CT (1 h) between December 2018 and December 2019 in Peking Union Medical College Hospital were retrospectively included. Taking clinical diagnosis as the standard, the results of visual score (≥2, positive) and semi-quantitative values (heart to contralateral lung (H/CL)≥1.5, positive) of 99Tc m-PYP uptake in dual-phase scintigraphy and SPECT/CT imaging were analyzed. One-way analysis of variance and Bonferroni test were used to analyze the data. Results:Among 31 patients with suspected CA, 15 were clinically diagnosed as CA (5 patients with transthyretin-related CA (ATTR-CA) and 10 patients with light chain CA (AL-CA)) and 16 were diagnosed as non-CA. All 5 patients with ATTR-CA had positive dual-phase scintigraphy and SPECT/CT imaging results. Three out of 10 patients with AL-CA had positive early-phase scintigraphy whereas negative delay-phase scintigraphy and SPECT/CT imaging results. Sixteen patients who were clinically diagnosed as non-CA had negative dual-phase scintigraphy and SPECT/CT imaging results. The sensitivity (5/5), specificity (10/10), positive predictive value (5/5), negative predictive value (10/10) and accuracy (15/15) of delay-phase scintigraphy and SPECT/CT imaging were the same. Among 31 patients, 16 patients carried transthyretin-related (TTR) gene mutation, and 4 of them who clinically diagnosed as variant ATTR (ATTRv) had positive image findings while 12 of them who not clinically diagnosed as CA had negative image findings. There were significant differences in H/CL between ATTR-CA group and AL-CA group in early-phase (2.11±0.24 vs 1.31±0.07) and delay-phase (2.02±0.19 vs 1.30±0.05; F values: 75.41 and 87.15, Bonferroni test, both P<0.01). Conclusions:99Tc m-PYP delay-phase scintigraphy and SPECT/CT have high diagnostic efficiencies in ATTR-CA, helping to determine the pathological classification of CA; while early-phase scintigraphy has false positive results. Moreover, 99Tc m-PYP imaging is helpful to detect CA in patients with TTR gene mutation.
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Objective:To evaluate the diagnostic value of 99Tc m-pyrophosphate (PYP) in transthyretin cardiac amyloidosis. Methods:From December 2018 to July 2019, 17 patients (9 males, 8 females, age: (53.4±13.0) years) with suspected cardiac amyloidosis underwent 99Tc m-PYP imaging in Peking Union Medical College Hospital were prospectively included. Visual score and semi-quantitative values (heart to contralateral ratio, H/CL) of 99Tc m-PYP uptake were used to diagnose transthyretin amyloidosis (ATTR). Biopsies and genetic measurements were also developed to evaluate the diagnostic value of the imaging. Results:Five of the 17 patients were diagnosed as ATTR with a visual score of 2-3, H/CL≥1.5, and confirmed with the biopsy or gene test. Four patients were diagnosed as ATTR with positive genetic results but no cardiac symptoms, and their visual scores were between 0 and 1 with H/CL<1.5. Considering the young age of the patients, amyloid deposition might have not yet caused visceral damage. Visual score of other 8 patients with negative 99Tc m-PYP imaging were also between 0 and 1 with H/CL<1.5, 2 of 8 were confirmed with light chain amyloidosis (AL) by biopsy, 3 were clinically diagnosed as AL and 3 were ATTR excluded. The accuracy of 99Tc m-PYP imaging for diagnosing ATTR was 11/11. Conclusion:99Tc m-PYP imaging is helpful for non-invasive diagnosis of transthyretin cardiac amyloidosis.
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Objective To synthesize 68 Ga-1,4,7,10-tetraazacyclododecane-N,N',N,N()-tetraacetic acid-D-Phe1-Tyr3-Thr8-octreotide (68Ga-DOTATATE) manually and automatically,validate its qualities in vitro,and evaluate its biodistribution in ICR mice and the microPET imaging in nude mice bearing pancreatic AR42J tumor.Methods 68Ga-DOTATATE was synthesized by automatic method using commercial metal isotope multifunctional module with strong cation exchange (SCX) column and by manual method.Both the products were measured for quality control.For the biodistribution study 5 groups of ICR mice were injected with 68Ga-DOTATATE(1.11 MBq) and executed at 10,30,60,120 and 240 min postinjection,respectively.The organs were weighted,and ％ ID/g was calculated.Nude mice bearing pancreatic AR42J tumor were intravenously injected with 3.7 MBq 68Ga-DOTATATE,and then microPET imaging was acquired at 10,30,60,120,18 and 240 min.Results 68Ga-DOTATATE could be successfully synthesized by the automatic and manual methods.Both the product injections were colorless and clear.The pH value was 6.5±0.1.For the products obtained from the two methods,the radiochemical purities were over 99％,and the products were stable for 4 h at room temperature.For the automatic method,68Ga-DOTATATE was synthesized within 30 min and with the radiochemical yield of (51.8±3.2)％ (time decay corrected).For the manual method,the time used for the synthesis was 20 min,and the labeling yield was over 99％.Three batches of the products were aseptic and pyrogen-free.In ICR mice,68Ga-DOTATATE was excreted by the kidney,and showed relatively high accumulation in the liver,spleen,pancreas and adrenal glands,while lower in the bone and soft tissue.The clearance from blood was fast with (4.41±0.81) ％ID/g at 10 min postinjection and (0.78 ± 0.32) ％ ID/g at 1 h.MicroPET imaging showed increased uptake of 68GaDOTATATE in the tumor tissues,and T/NT were 2.01±0.29(10 min),6.74±2.90(30 min) and 4.46±2.05 (60 min),respectively.Conclusions 68 Ga-DOTATATE could be successfully synthesized manually and automatically.The products reach to the specification of radioactive drugs and could be used as an attractive positron emitting radiotracer for detection of the somatostatin receptor-positive tumors.
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Objective To evaluate the effectiveness and safety of higenamine (HG),a pharmaco logical stress agent,for the detection of myocardial ischemia using SPECT.Methods This study was an open,multi-center,randomized and positively controlled trial with crossover references.It consisted of 120patients clinically confirmed or suspected of myocardial ischemia.Each patient underwent a resting MPI and two separate stress MPI in a randomized crossover manner with intravenous administration of HG or adenosine (Ad) on different days.The severity and extent of myocardial ischemia were diagnosed on stress MPI.The degree of vascular stenosis in terms of percentage narrowing was measured by CAG (＞50％ was defined as coronary disease),thus defined as gold standard.The diagnostic efficacy of HG and Ad was compared.Vital signs,routine blood and urine tests,blood biochemical items and side effects were documented for evaluation of procedure safety.Two-sample t test,x2 or Fisher's exact test,and Kappa test were used.Results A total of 109 patients completed the trim and CAG.The diagnostic sensitivity,specificity,accuracy,positive predictive value,negative predictive value of HG MPI were 56.1％ (32/57),78.8％ (41/52),67.0％(73/109),74.4％ (32/43) and 62.1％ (41/66),respectively,which were not significantly different from those ofAd MPI (52.6％ (30/57),82.7％ (43/52),67.0％ (73/109),76.9％ (30/39) and 61.4％(43/70) ;x2 =0-0.2476,all P＞0.05).The sensitivity of HG vs Ad MPI in the diagnosis of single-,double-and triple-vessel ischemia was 29.6％ (8/27) vs 22.2％ (6/27),64.7％ (11/17) vs 64.7％ (11/17)and 100％ (13/13) vs 100％ (13/13),respectively.The concordance between HG and Ad for the detection of LAD,LCX and RCA ischemia was 95.41％ (104/109),97.25％ (106/109) and 97.25％ (106/109) (Kappa=0.8905,0.8420 and 0.8874).HG did not induce significant systolic blood pressure change during or after administration.Both HG and Ad could induce temporary decrease of diastolic blood pressure.Either HG or Ad induced significantly increased HR during administration and 5 min after administration.The clinical laboratory profile (hematology,serum chemistry,and urinalysis) was either normal or with no significant change.A total of 176 side effects (e.g,dyspnea,short breath,palpitation,dizziness,headache) were found related to HG (69.2％,83/120) and Ad (77.5％,93/120) administration (x2=2.1307,P＞0.05),which were mostly mild and transient.Conclusion HG is a safe and effective pharmacological stress test agent as compared to adenosine for the detection of CAD with SPECT perfusion imaging.
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Small animal PET is a quantitative imaging technique that can noninvasive and dynamically image the distribution of positron-labeled radiopharmaceuticals in vivo,therefore representing a new means of providing information for drug development and evaluation.This article reviews the fundamental basis of PET imaging and their application in preclinical drug discovery and development.