3D image-based dosimetry for Yttrium-90 radioembolization of hepatocellular carcinoma: Impact of imaging method on absorbed dose estimates

BackgroundTo improve therapy outcome of Yttrium-90 selective internal radiation therapy (⁹⁰Y SIRT), patient-specific post-therapeutic dosimetry is required. For this purpose, various dosimetric approaches based on different available imaging data have been reported. The aim of this work was to compare post-therapeutic 3D absorbed dose images using Technetium-99m (^99mTc) MAA SPECT/CT, Yttrium-90 (⁹⁰Y) bremsstrahlung (BRS) SPECT/CT, and ⁹⁰Y PET/CT.MethodsTen SIRTs of nine patients with unresectable hepatocellular carcinoma (HCC) were investigated. The ^99mTc SPECT/CT data, obtained from ^99mTc-MAA-based treatment simulation prior to ⁹⁰Y SIRT, were scaled with the administered ⁹⁰Y therapy activity. 3D absorbed dose images were generated by dose kernel convolution with scaled ^99mTc/⁹⁰Y SPECT/CT, ⁹⁰Y BRS SPECT/CT, and ⁹⁰Y PET/CT data of each patient. Absorbed dose estimates in tumor and healthy liver tissue obtained using the two SPECT/CT methods were compared against ⁹⁰Y PET/CT.ResultsThe percentage deviation of tumor absorbed dose estimates from ⁹⁰Y PET/CT values was on average −2 ± 18% for scaled ^99mTc/⁹⁰Y SPECT/CT, whereas estimates from ⁹⁰Y BRS SPECT/CT differed on average by −50 ± 13%. For healthy liver absorbed dose estimates, all three imaging methods revealed comparable values.ConclusionThe quantification capabilities of the imaging data influence ⁹⁰Y SIRT tumor dosimetry, while healthy liver absorbed dose values were comparable for all investigated imaging data. When no ⁹⁰Y PET/CT image data are available, the proposed scaled ^99mTc/⁹⁰Y SPECT/CT dosimetry method was found to be more appropriate for HCC tumor dosimetry than ⁹⁰Y BRS SPECT/CT based dosimetry.     

99mTc标记BmK CT及其胶质瘤荷瘤裸鼠的SPECT成像研究

目的:通过放射性核素~(99m)Tc标记BmK CT多肽制备靶向胶质瘤的显像剂,探讨~(99m)?Tc-BmK CT用于胶质瘤显像的可行性。方法:采用BmK CT多肽游离的氨基与DTPA酸酐反应得到BmK CT-DTPA,经99m Tc标记后通过柱层析分离纯化制备~(99m)?Tc-BmK CT。测定标记物在PBS溶液和血清中不同时间点放射性化学纯度,评价BmK CT-~(99m)?Tc体外稳定性。新西兰白兔耳缘静脉注射~(99m)Tc-BmK CT进行SPECT显像,观察不同时间点体内的放射性分布。皮下胶质瘤裸鼠经尾静脉注射~(99m)Tc-BmK CT,观察不同时间点肿瘤的摄取情况;注射后4 h处死裸鼠,分离肿瘤和主要器官进行离体SPECT显像,并用勾画感兴趣区法分析相对放射性计数。结果:~(99m)Tc标记BmK CT多肽标记率大于80%,经柱层析分离纯化后放射性化学纯度大于99%。标记物在PBS和血清稳定性良好,6 h内放射性化学纯度均大于95%,12 h内放射性化学纯度大于90%。正常白兔SPECT显像表明~(99m)Tc-BmK CT主要浓聚在肝脏、脾脏和肾脏,软组织持续显影微弱,甲状腺区及胃肠未见核素浓聚;显像剂主要通过泌尿系统排泄,24 h肾脏与肝脏显影接近。胶质瘤裸鼠SPECT显像表明,注射后4 h肿瘤显像清楚,ROI分析结果显示肿瘤/肌肉比4.26±0.25,标记物在肿瘤内代谢缓慢,8 h肿瘤部位仍有较高摄取。结论:本研究成功制备了~(99m)Tc标记BmK CT多肽,标记物主要被肝、脾和肾摄取,经泌尿系统排泄;~(99m)Tc-BmK CT能够在皮下胶质瘤中浓聚,注射后4 h肿瘤显影清晰,瘤内代谢缓慢,有潜力成为一种新型胶质瘤分子探针。     

Comparison of 90Y SIRT predicted and delivered absorbed doses using a PSF conversion method

PurposeThe aims of this study were to develop and apply a method to correct for the differences in partial volume effects of pre-therapy Technetium-99 m (^99mTc)-MAA SPECT and post-therapy Yttrium-90 (⁹⁰Y) bremsstrahlung SPECT imaging in selective internal radiation therapy, and to use this method to improve quantitative comparison of predicted and delivered ⁹⁰Y absorbed doses.MethodsThe spatial resolution of ^99mTc SPECT data was converted to that of ⁹⁰Y SPECT data using a function calculated from ^99mTc and ⁹⁰Y point spread functions. This resolution conversion method (RCM) was first applied to ^99mTc and ⁹⁰Y SPECT phantom data to validate the method, and then to clinical data to assess the power of ^99mTc SPECT imaging to predict the therapeutic absorbed dose.ResultsThe maximum difference between absorbed doses to phantom spheres was 178%. This was reduced to 27% after the RCM was applied.The clinical data demonstrated differences within 38% for mean absorbed doses delivered to the normal liver, which were reduced to 20% after application of the RCM. Analysis of clinical data showed that therapeutic absorbed doses delivered to tumours greater than 100 cm³ were predicted to within 52%, although there were differences of up to 210% for smaller tumours, even after the RCM was applied.ConclusionsThe RCM was successfully verified using phantom data. Analysis of the clinical data established that the ^99mTc pre-therapy imaging was predictive of the ⁹⁰Y absorbed dose to the normal liver to within 20%, but had poor predictability for tumours smaller than 100 cm³.     

Validation of irtGPUMCD,a GPU-based Monte Carlo internal dosimetry framework for radionuclide therapy

PurposeMonte Carlo (MC) simulations are highly desirable for dose treatment planning and evaluation in radiation oncology. This is true also in emerging nuclear medicine applications such as internal radiotherapy with radionuclides. The purpose of this study is the validation of irtGPUMCD, a GPU-based MC code for dose calculations in internal radiotherapy.MethodsThe female and male phantoms of the International Commission on Radiological Protection (ICRP 110) were used as benchmarking geometries for this study focused on ¹⁷⁷Lu and including ^99mTc and ¹³¹I. Dose calculations were also conducted for a real patient. For phantoms, twelve anatomical structures were considered as target/source organs. The S-values were evaluated with irtGPUMCD simulations (10⁸ photons), with gamma branching ratios of ICRP 107 publication. The ¹⁷⁷Lu electrons S-values were calculated for source organs only, based on local deposition of dose in irtGPUMCD. The S-value relative difference between irtGPUMCD and IDAC-DOSE were evaluated for all targets/sources considered. A DVHs comparison with GATE was conducted. An exponential track length estimator was introduced in irtGPUMCD to increase computational efficiency.ResultsThe relative S-value differences between irtGPUMCD and IDAC-DOSE were <5% while this comparison with GATE was <1%. The DVHs dosimetric indices comparison between GATE and irtGPUMCD for the patient led to an excellent agreement (<2%). The time required for the simulation of 10⁸ photons was 1.5 min for the female phantom, and one minute for the real patient (<1% uncertainty). These results are promising and let envision the use of irtGPUMCD for internal dosimetry in clinical applications.     

Effect of image registration on 3D absorbed dose calculations in 177Lu-DOTATOC peptide receptor radionuclide therapy

Peptide receptor radionuclide therapy (PRRT) is an effective MRT (molecular radiotherapy) treatment, which consists of multiple administrations of a radiopharmaceutical labelled with ¹⁷⁷Lu or ⁹⁰Y. Through sequential functional imaging a patient specific 3D dosimetry can be derived. Multiple scans should be previously co-registered to allow accurate absorbed dose calculations. The purpose of this study is to evaluate the impact of image registration algorithms on 3D absorbed dose calculation.A cohort of patients was extracted from the database of a clinical trial in PRRT. They were administered with a single administration of ¹⁷⁷Lu-DOTATOC. All patients underwent 5 SPECT/CT sequential scans at 1 h, 4 h, 24 h, 40 h, 70 h post-injection that were subsequently registered using rigid and deformable algorithms. A similarity index was calculated to compare rigid and deformable registration algorithms. 3D absorbed dose calculation was carried out with the Raydose Monte Carlo code.The similarity analysis demonstrated the superiority of the deformable registrations (p < .001).Average absorbed dose to the kidneys calculated using rigid image registration was consistently lower than the average absorbed dose calculated using the deformable algorithm (90% of cases), with percentage differences in the range [−19; +4]%. Absorbed dose to lesions were also consistently lower (90% of cases) when calculated with rigid image registration with absorbed dose differences in the range [−67.2; 100.7]%. Deformable image registration had a significant role in calculating 3D absorbed dose to organs or lesions with volumes smaller than 100 mL.Image based 3D dosimetry for ¹⁷⁷Lu-DOTATOC PRRT is significantly affected by the type of algorithm used to register sequential SPECT/CT scans.     

Generation of clinical 177Lu SPECT/CT images based on Monte Carlo simulation with GATE

PurposePatient-specific dosimetry in MRT relies on quantitative imaging, pharmacokinetic assessment and absorbed dose calculation. The DosiTest project was initiated to evaluate the uncertainties associated with each step of the clinical dosimetry workflow through a virtual multicentric clinical trial. This work presents the generation of simulated clinical SPECT datasets based on GATE Monte Carlo modelling with its corresponding experimental CT image, which can subsequently be processed by commercial image workstations.MethodsThis study considers a therapy cycle of 6.85 GBq ¹⁷⁷Lu-labelled DOTATATE derived from an IAEA-Coordinated Research Project (E23005) on “Dosimetry in Radiopharmaceutical therapy for personalised patient treatment”. Patient images were acquired on a GE Infinia-Hawkeye 4 gamma camera using a medium energy (ME) collimator. Simulated SPECT projections were generated based on experimental time points and validated against experimental SPECT projections using flattened profiles and gamma index. The simulated projections were then incorporated into the patient SPECT/CT DICOM envelopes for processing and their reconstruction within a commercial image workstation.ResultsGamma index passing rate (2% − 1 pixel criteria) between 95 and 98% and average gamma between 0.28 and 0.35 among different time points revealed high similarity between simulated and experimental images. Image reconstruction of the simulated projections was successful on HERMES and Xeleris workstations, a major step forward for the initiation of a multicentric virtual clinical dosimetry trial based on simulated SPECT/CT images.ConclusionsRealistic ¹⁷⁷Lu patient SPECT projections were generated in GATE. These modelled datasets will be circulated to different clinical departments to perform dosimetry in order to assess the uncertainties in the entire dosimetric chain.     

Optimisation of reconstruction,volumetry and dosimetry for 99mTc-SPECT and 90Y-PET images: Towards reliable dose-volume histograms for selective internal radiation therapy with 90Y-microspheres

PurposeIn Selective Internal Radiation Therapy (SIRT), ^99mTc-MAA SPECT images are commonly used to predict microspheres distribution but recent works used ⁹⁰Y-microspheres PET images. Nevertheless, evaluation of the predictive power of ^99mTc-MAA has been hampered by the lack of reliable comparisons between ^99mTc-SPECT and ⁹⁰Y-PET images. Our aim was to determine the “in situ” optimisation procedure in order to reliably compare ^99mTc-SPECT and ⁹⁰Y-PET images and achieve optimal personal dosimetry.MethodsWe acquired ^99mTc-SPECT/CT and ⁹⁰Y-PET/CT images of NEMA and Jaszczak phantoms. We found the best reconstruction parameters for quantification and for volume estimations. We determined adaptive threshold curves on the volumetric reconstruction. We copied the optimised volumes on the quantitative reconstruction, named here the “cross volumes” technique. Finally, we compared ^99mTc-SPECT and ⁹⁰Y-PET Dose Volume Histograms.ResultsOur “in situ” optimisation procedure decreased errors on volumes and quantification (from −44.2% and −15.8% to −3.4% and −3.28%, respectively, for the 26.5 mL PET phantom sphere). Moreover, ^99mTc-SPECT and ⁹⁰Y-PET DVHs were equivalent only after the optimisation procedure (difference in mean dose <5% for the three biggest spheres).ConclusionsThis work showed that a preliminary “in situ” phantom study was necessary to optimise volumes and quantification of ^99mTc-SPECT and ⁹⁰Y-PET images and allowed to achieve a reliable comparison between patient treatment planning and post implant dosimetry, notably by the use of the “cross volumes” technique. Methodology developed in this work will enable robust evaluations of the predictive power of ^99mTc-SPECT, as well as dose-response relationship and side effects in SIRT treatments.     

Radiolabeling of lipid-based nanoparticles for diagnostics and therapeutic applications: a comparison using different radiometals

Radiolabeling of nanoparticles (NPs) has been performed for a variety of reasons, such as for studying pharmacokinetics, for imaging, or for therapy. Here, we describe the in vitro and in vivo evaluation of DTPA-derivatized lipid-based NP (DTPA-NP) radiolabeled with different radiometals, including ¹¹¹In and ^99mTc, for single-photon emission computed tomography (SPECT), ⁶⁸Ga for positron emission tomography (PET), and ¹⁷⁷Lu for therapeutic applications. PEGylated DTPA-NP with varying DTPA amounts, different composition, and size were radiolabeled with ¹¹¹In, ¹⁷⁷Lu, and ⁶⁸Ga, using various buffers. ^99mTc-labeling was performed directly and by using the carbonyl aquaion, [^99mTc(H₂O)₃(CO)₃]⁺. Stability was tested and biodistribution evaluated. High labeling yields (>90%) were achieved for all radionuclides and different liposomal formulations. Specific activities (SAs) were highest for ¹¹¹In (>4 MBq/μg liposome), followed by ⁶⁸Ga and ¹⁷⁷Lu; for ^99mTc, high labeling yields and SA were only achieved by using [^99mTc(H₂O)₃(CO)₃]⁺. Stability toward DTPA/histidine and in serum was high (>80 % RCP, 24 hours postpreparation).). Biodistribution in Lewis rats revealed no significant differences between NP in terms of DTPA loading and particle composition; however, different uptake patterns were found between the radionuclides used. We observed lower retention in blood (<3.3 %ID/g) and lower liver uptake (< 2.7 %ID/g) for ^99mTc- and ⁶⁸Ga, compared to ¹¹¹In-NP (blood, <4 %ID/g; liver, <3.6 %ID/g). Imaging potential was shown by both PET magnetic resonance imaging fusion imaging and SPECT imaging. Overall, our study shows that PEGylated DTPA-NP are suitable for radiolabeling studies with a variety of radiometals, thereby achieving high SA suitable for targeting applications.     

Metastatic melanoma imaging using a novel Tc-99m-labeled lactam-cyclized alpha-MSH peptide

The purpose of this study was to determine the metastatic melanoma imaging property of ^99mTc(EDDA)-HYNIC-Aoc-Nle-CycMSH_hex {hydrazinonicotinamide-8-aminooctanoic acid-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH₂}. HYNIC-Aoc-Nle-CycMSH_hex was synthesized using fluorenylmethyloxy carbonyl (Fmoc) chemistry. The IC₅₀ value of HYNIC-Aoc-Nle-CycMSH_hex was 0.78?±?0.13?nM for B16/F10 melanoma cells. ^99mTc(EDDA)-HYNIC-Aoc-Nle-CycMSH_hex displayed significantly higher uptake (14.26?±?2.74 and 10.45?±?2.31%?ID/g) in B16/F10 metastatic melanoma-bearing lung than that in normal lung (0.90?±?0.15 and 0.53?±?0.14%?ID/g) at 2 and 4?h post-injection, respectively. B16/F10 pulmonary metastatic melanoma lesions were clearly visualized by SPECT/CT using ^99mTc(EDDA)-HYNIC-Aoc-Nle-CycMSH_hex as an imaging probe at 2?h post-injection, underscoring its potential as an imaging probe for metastatic melanoma detection.     

Technetium-99m monoclonal antibody fragment (FAb) scintigraphy in the evaluation of small cell lung cancer: a preliminary report

Small cell lung cancer (SCC) has the most rapid growth rate of the four cell types and metastasizes early. Present imaging modalities for staging include chest x-ray, CT, MRI and bone scans. In this preliminary study, we assessed the clinical role of ^99mTc-monoclonal antibody (MOAB) scintigraphy in five patients with histologically proven SCC. Each patient was infused with 20–30 mCi of ^99mTc labeled Fab fragment of MOAB (NR-LU-10, NeoRx, Seattle, Wash.). Total body simultaneous anterior and posterior images were obtained 14–16 h post injection. SPECT images of the chest were obtained through a 360 ° rotation of the gamma camera and recorded on a 62 × 64 × 16 matrix. Images (1.2cm thick) were generated in transaxial, sagittal and coronal views.Fourteen of fifteen chest lesions detected by CT were confirmed by ^99mTc MOAB scintigraphy. Scintigraphy detected one additional chest lesion not seen by CT. Scintigraphy failed to detect a brain lesion (2 cm), a chest lesion, and two adrenal lesions, all of which were seen by CT. In one patient with multiple (more than 10) lesions in the liver, both scintigraphy and CT detected all lesions. Three spine lesions seen on ^99mTc MDP scan and positive for metastasis on MRI concentrated ^99mTc MOAB, but two rib lesions seen on ^99mTc MDP bone scan did not concentrate ^99mTc MOAB. It is concluded from these preliminary results that the potential usefulness of ^99mTc MOAB scintigraphy as a complementary imaging modality in the staging of small cell lung cancer should be investigated further.     

188Re image performance assessment using small animal multi-pinhole SPECT/PET/CT system

PurposeThe goal of this study was to investigate the performance of a pre-clinical SPECT/PET/CT system for ¹⁸⁸Re imaging.MethodsPhantom experiments were performed aiming to assess the characteristics of two multi-pinhole collimators: ultra-high resolution collimator (UHRC) and high-energy ultra high resolution collimator (HE-URHC) for imaging ¹⁸⁸Re. The spatial resolution, image contrast and contrast-to-noise ratio (CNR) were investigated using micro-Jaszczak phantoms. Additionally, the quantification accuracy of ¹⁸⁸Re images was evaluated using two custom-designed phantoms. The ¹⁸⁸Re images were compared to those obtained with ^99mTc (gold standard); the acquired energy spectra were analyzed and Monte-Carlo simulations of the UHRC were performed. To verify our findings, a C57BL/6-mouse was injected with ¹⁸⁸Re-microspheres and scanned with both collimators.ResultsThe spatial resolution achieved in ¹⁸⁸Re images was comparable to that of ^99mTc. Acquisitions using HE-UHRC yielded ¹⁸⁸Re images with higher contrast and CNR than UHRC. Studies of quantitative accuracy of ¹⁸⁸Re images resulted in <10% errors for both collimators when the activity was calculated within a small VOI around the object of interest. Similar quantification accuracy was achieved for ^99mTc. However, ¹⁸⁸Re images showed much higher levels of noise in the background. Monte-Carlo simulations showed that ¹⁸⁸Re imaging with UHRC is severely affected by down-scattered photons from high-energy emissions. The mouse images showed similar biodistribution of ¹⁸⁸Re-microspheres for both collimators.ConclusionsVECTor/CT provided ¹⁸⁸Re images quantitatively accurate and with quality comparable to ^99mTc. However, due to large penetration of UHRC by high-energy photons, the use of the HE-UHRC for imaging ¹⁸⁸Re in VECTor/CT is recommended.     

Development of 99mTc-labeled asymmetric urea derivatives that target prostate-specific membrane antigen for single-photon emission computed tomography imaging

Prostate-specific membrane antigen (PSMA) is expressed strongly in prostate cancers and is, therefore, an attractive diagnostic and radioimmunotherapeutic target. In contrast to previous reports of PMSA-targeting ^99mTc-tricarbonyl complexes that are cationic or lack a charge, no anionic ^99mTc-tricarbonyl complexes have been reported. Notably, the hydrophilicity conferred by both cationic and anionic charges leads to rapid hepatobiliary clearance, whereas an anionic charge might better enhance renal clearance relative to a cationic charge. Therefore, an improvement in rapid clearance would be expected with either cationic or anionic charges, particularly anionic charges. In this study, we designed and synthesized a novel anionic ^99mTc-tricarbonyl complex ([^99mTc]TMCE) and evaluated its use as a single-photon emission computed tomography (SPECT) imaging probe for PSMA detection. Direct synthesis of [^99mTc]TMCE from dimethyl iminodiacetate, which contains both the asymmetric urea and succinimidyl moiety important for PSMA binding, was performed using our microwave-assisted one-pot procedure. The chelate formation was successfully achieved even though the precursor included a complicated bioactive moiety. The radiochemical yield of [^99mTc]TMCE was 12–17%, with a radiochemical purity greater than 98% after HPLC purification. [^99mTc]TMCE showed high affinity in vitro, with high accumulation in LNCaP tumors and low hepatic retention in biodistribution and SPECT/CT studies. These findings warrant further evaluation of [^99mTc]TMCE as an imaging agent and support the benefit of this strategy for the design of other PSMA imaging probes.     

Cystic Parathyroid Adenomas: An Enigmatic Entity and Role of Tc-99 m Sestamibi Scintigraphy

ObjectiveFunctional cystic lesion of the parathyroid gland is a rare cause of primary hyperparathyroidism (PHPT). They have been postulated to arise from the hemorrhage and cystic degeneration in the parathyroid adenoma (PA). We intended to analyze their scintigraphic and histopathological findings since available literature is sparse.MethodsDual-phase ^{99 m}Tc-sestamibi planar and SPECT/CT scans performed from January 2014 to January 2020 in patients presenting with PHPT were retrospectively analyzed. The clinical, biochemical, and ultrasound features were collected. Planar and SPECT/CT imaging parameters were analyzed. Detailed histopathological analysis, along with post-surgical clinical and biochemical features of the patients who underwent surgery, was reviewed with a mean follow-up of 21.8 ± 20.1 months.ResultsOf the 979 scans analyzed, 10 showed cystic parathyroid lesions (M:F- 3:7, mean age 45.6 ± 15 years, range: 23-66). The predominant presenting features in patients were abdominal pain and renal stone disease, present in 60% of the patients. On planar scintigraphy, 90% of the patients had tracer avid distinct lesions, whereas tracer activity was seen in the solid part of the cystic lesions in all 10 patients on SPECT/CT, with cystic areas showing an attenuation of 23.1 ± 7.6 HU. Eight of these patients underwent surgery, with all showing PA with cystic changes on histopathology. Two of these patients also showed hemorrhage within the cystic spaces.ConclusionHemorrhage within a PA may give rise to cystic parathyroid lesions with PHPT. ^{99 m}Tc-sestamibi scintigraphy with dual-phase imaging and SPECT/CT may help in detecting this rare entity.     

Scintigraphie pulmonaire pour suspicion d’embolie pulmonaire aiguë : état des lieux des pratiques en France en 2014

AimThe aim of this study was to assess lung scintigraphy practices in France for the diagnosis of acute pulmonary embolism, especially regarding the proportion of centers using single photon emission computed tomography (SPECT) rather than planar ventilation/perfusion (V/Q) imaging.Materials and methodsAn online survey composed of simple multiple-choice questions was distributed to the 210 french nuclear medicine departments in April and May 2014. The survey covered image acquisition, interpretation criteria for SPECT and planar images, and use of pseudoplanar images and radiopharmaceuticals. Departments were initially solicited by 2 sets of e-mails. They were subsequently contacted by phone. A single response per department was consolidated.ResultsTwo hundred nine responses were collected (participation rate: 99.5%). Sixty-seven percent of french centers indicated use of V/Q SPECT in routine practice. The first intention acquisition protocol was SPECT/CT in 34%, SPECT in 26% and V/Q planar in 34%. The most commonly used criteria for SPECT interpretation were those of the EANM (63%). Criteria used for planar interpretation were heterogeneous (EANM criteria, 39%; no standardized criteria, 28%; PIOPED, 23%). Eighty-three percent of centers used ^99mTc aerosol and 17% ^81mKr.ConclusionThis survey shows that SPECT has largely replaced planar imaging for PE diagnosis with lung scintigraphy. Acquisition protocols and interpretation criteria are inconsistent (especially for planar imaging).     

Simultaneous dual-isotope 123I/99mTc acquisition using CZT-based cameras: Toward a one-stop-shop SPECT in heart failure patients

The CZT-cameras (DNM 530c and DSPECT) have only recently been introduced, and the impact of the increased energy resolution remains unknown. This paper summarizes the evidence on the assessment of: (i) the left ventricular function, (ii) the ¹²³I/^99mTc mismatch, and (iii) the heart-to-mediastinum ratio (HMR) of ¹²³I-metaiodobenzylguanidine (MIBG) uptake under dual-isotope conditions (^99mTc and ¹²³I) using cadmium-zinc-telluride (CZT) technology. The diagnostic accuracy of CZT cameras for myocardial sympathetic innervation imaging, left ventricular function and perfusion assessment using perfusion-gated SPECT have only been established in a few studies, under single-isotope conditions. Limited evidence is available regarding simultaneous dual-isotope acquisition using CZT-cameras. However, recently reported data have shown that CZT cameras allow, in dual-isotope (¹²³I and ^99mTc) acquisitions and under routine conditions: (i) a simultaneous and accurate segmental study of myocardial innervation and perfusion (match and mismatch), (ii) the ventricular function assessment (EDV, ESV and LVEF), and (iii) the determination of the late HMR of cardiac ¹²³I-MIBG uptake in patients with heart failure. However, this latter should be performed using transaxial reconstructed images and a linear correction based on phantom data acquisitions.

Influence of voxel S factors on three-dimensional internal dosimetry calculations

Internal dosimetry is a fundamental instrument for the personalization of nuclear medicine therapies, to maximize the therapeutic effect while minimizing the radiation burden to other organs. Three-dimensional (3D) dosimetry can quantify the impact of heterogeneous radiopharmaceutical distributions in organs, lesions and tissues.We analysed the influence of radionuclide voxel S factors in 3D dosimetry of ¹¹¹In, ¹⁷⁷Lu and ⁹⁰Y, the most used radionuclides in Peptide Receptor Radionuclide Therapy (PRRT). Calculations were carried out for kidneys on a workstation equipped with a software for 3D dosimetry (Imalytics STRATOS, Philips AG), adopting a computational anthropomorphic phantom and, retrospectively, the SPECT-CT image series of a clinical case of PRRT.Two sets of voxel S factors were adopted: the pre-loaded Philips kernels, calculated by direct Monte Carlo simulation, and the ones calculated through a previously proposed analytical approach. Philips ¹¹¹In kernel did not account for mono-energetic Auger or Conversion electrons.Results indicate a difference of about −32% in voxel S factors for ¹¹¹In in 4.42 mm voxel size and around −35% in 4.80 mm voxel size, particularly self-dose values; this lead to significant shift in dose histograms and average doses. For ¹⁷⁷Lu and ⁹⁰Y, differences are about 2% and 12% for 4.42 mm voxels and about −8% and 9% for 4.80 mm voxels, respectively, attributable to the different calculation methods of the voxel S factors; this does not lead to significant discrepancies between the two dose histograms. Consequently, voxel S factors must account accurately for all radiations emitted by the nuclide.     

Synthesis and biological evaluation of a novel 99mTc(CO)3 complex of ciprofloxacin dithiocarbamate as a potential agent to target infection

The ciprofloxacin dithiocarbamate (CPFXDTC) was radiolabeled with [^99mTc(CO)₃(H₂O)₃]⁺ intermediate to form the ^99mTc(CO)₃–CPFXDTC complex in high yield. The ^99mTc(CO)₃–CPFXDTC complex was characterized by HPLC and its stability in serum was studied. Its partition coefficient indicated that it was a lipophilic complex. The bacterial binding efficiency of ^99mTc(CO)₃–CPFXDTC was almost the same as that of ^99mTcN–CPFXDTC, and was higher than that of ^99mTc–ciprofloxacin. Biodistribution results in induced infection mice showed ^99mTc(CO)₃–CPFXDTC had higher uptake at the sites of infection and better abscess/blood and abscess/muscle ratios than those of ^99mTc–ciprofloxacin and ^99mTcN–CPFXDTC. Single photon emission computed tomography (SPECT) static imaging study in infected rabbits demonstrated the uptake in the left thigh infection lesion was observable, while no accumulation in the right thigh muscle was found. These results suggested ^99mTc(CO)₃–CPFXDTC would be a promising candidate for further evaluation as infection imaging agent.     

An Exploratory Study on 99mTc-RGD-BBN Peptide Scintimammography in the Assessment of Breast Malignant Lesions Compared to 99mTc-3P4-RGD2

Purpose

This study aimed to explore the diagnostic performance of single photon emission computed tomography / computerized tomography (SPECT/CT) using a new radiotracer ^99mTc-RGD-BBN for breast malignant tumor compared with ^99mTc-3P4-RGD₂.

Methods

6 female patients with breast malignant tumors diagnosed by fine needle aspiration cytology biopsy (FNAB) who were scheduled to undergo surgery were included in the study. ^99mTc-3P4-RGD₂ and ^99mTc-RGD-BBN were performed with single photon emission computed tomography (SPECT) at 1 hour after intravenous injection of 299 ± 30 MBq and 293 ± 32 MBq of radiotracers respectively at separate day. The results were evaluated by the Tumor to non-Tumor ratios (T/NT). ^99mTc-RGD-BBN and ^99mTc-3P4-RGD₂ SPECT/CT images were interpreted independently by 3 experienced nuclear medicine physicians using a 3-point scale system. All of the samples were analyzed immunohistochemically to evaluate the integrin αvβ3 and gastrin-releasing peptide receptor (GRPR) expression. The safety, biodistribution and radiation dosimetry of ^99mTc-RGD-BBN were also evaluated in the healthy volunteers.

Results

No serious adverse events were reported in any of the patients during the study. The effective radiation dose entirely conformed to the relevant standards. A total of 6 palpable malignant lesions were detected using ^99mTc-RGD-BBN SPECT/CT with clear uptake. All malignant lesions were also detected using ^99mTc-3P4-RGD₂ SPECT/CT. The results showed that five malignant lesions were with clear uptake and the other one with barely an uptake. 4 malignant cases were found with both αvβ3 and GRPR expression, 1 case with only GRPR positive expression (integrin αvβ3 negative) and 1 case with only integrin αvβ3 positive expression (GRPR negative).

Conclusion

^99mTc-RGD-BBN is a safe agent for detecting breast cancer. ^99mTc-RGD-BBN may have the potential to make up for the deficiency of ^99mTc-3P4-RGD₂ in the detection of breast cancer with only GRPR positive expression (integrin α_vβ₃ negative). The preliminary application of ^99mTc-RGD-BBN has demonstrated its powerful potential in breast cancer diagnosis and therapy.     

99mTc(Cu)—mannitol complex: a new agent for dynamic renal function studies

Mannitol has been labelled with ^99mTc by using cuprous chloride as a reducing agent. Blood and kidney clearance of ^99mTc(Cu)-mannitol was slightly faster than that of ^99mTc(Sn)-DTPA in rat and maximum radioactivity ratio of kidneys to blood was 84.6 at 5 min. A comparative study of ^99mTc(Cu)-mannitol, ^99mTc(Sn)-DTPA was made in rabbits by taking serial images of kidneys and bladder with a γ camera. Results show superiority of ^99mTc(Cu)-mannitol over other agents for dynamic renal function studies.     

Synthesis and evaluation of 99mTc–2-[(3-carboxy-1-oxopropyl)amino]-2-deoxy-d-glucose as a potential tumor imaging agent

The 2-[(3-carboxy-1-oxopropyl)amino]-2-deoxy-d-glucose (CPADG) was synthesized and radiolabeled with ^99mTcO₄⁻ to obtain the ^99mTc–CPADG complex in high yield. It was stable over 6 h in saline at room temperature and in serum at 37 °C. The partition coefficient and electrophoresis results indicated that the complex was hydrophilic and cationic. In vitro cell studies showed there was an increase in the uptake of ^99mTc–CPADG as a function of incubation time and ^99mTc–CPADG was possibly transported via the glucose transporters. The biodistribution of ^99mTc–CPADG in mice bearing S 180 tumor showed that the complex accumulated in the tumor with high uptake and good retention. The tumor/blood and tumor/muscle ratios increased with time and reached 1.91 and 5.05 at 4 h post-injection. Single photon emission computed tomography (SPECT) image studies showed there was an obvious accumulation in tumor sites, suggesting ^99mTc–CPADG would be a promising candidate for tumor imaging.