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A Microdosing Study with ^99mTc-PHC-102 for the SPECT/CT Imaging of Primary and Metastatic Lesions in Renal Cell Carcinoma Patients.

ABSTRACT: ^99mTc-PHC-102 is a ^99mTc-labeled derivative of acetazolamide, a high-affinity small organic ligand of carbonic anhydrase IX (CAIX). ^99mTc-PHC-102 has previously shown favorable in vivo biodistribution properties in mouse models of CAIX-positive clear cell renal cell carcinoma (ccRCC) and colorectal cancer. In this study, we aimed to explore the targeting performance of ^99mTc-PHC-102 in SPECT in patients with renal cell carcinoma while also assessing the safety and tolerability of the radiotracer. Methods: We studied 5 patients with localized or metastatic ccRCC in a microdosing regimen, after the administration of a 50-μg total of CAIX ligand and 600-800 MBq of ^99mTc-PHC-102. Tissue distribution and residence time in normal organs and tumors were analyzed by serial SPECT/CT scans at 3 time points (30 min, 2 h, and 6 h) after intravenous administration. Results: In the 5 patients studied, ^99mTc-PHC-102 was well tolerated and no study drug-related adverse events were recorded. In the stomach, kidneys, and gallbladder, the radiotracer showed a rapid initial uptake, which cleared over time. Localization of the study drug in primary tumors of 5 patients was observed, with favorable tumor-to-background ratios. ^99mTc-PHC-102 SPECT/CT allowed the identification of 4 previously unknown lung and lymph node metastases in 2 patients. Conclusion: ^99mTc-PHC-102 is a promising SPECT tracer for the imaging of patients with ccRCC. This tracer has the potential to identify primary and metastatic lesions in different anatomic locations. ^99mTc-PHC-102 might also serve as a companion diagnostic agent for future CAIX-targeting therapeutics.

SUBMITTER: Kulterer OC

PROVIDER: S-EPMC8049338 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe introduction of hybrid SPECT/CT devices enables quantitative imaging in SPECT, providing a methodological setup for quantitation using SPECT tracers comparable to PET/CT. We evaluated a specific quantitative reconstruction algorithm for SPECT data using a 99mTc-filled NEMA phantom. Quantitative and qualitative image parameters were evaluated for different parametrizations of the acquisition and reconstruction protocol to identify an optimized quantitative protocol.ResultsThe reconstructed activity concentration (ACrec) and the signal-to-noise ratio (SNR) of all examined protocols (n = 16) were significantly affected by the parametrization of the weighting factor k used in scatter correction, the total number of iterations and the sphere volume (all, p < 0.0001). The two examined SPECT acquisition protocols (with 60 or 120 projections) had a minor impact on the ACrec and no significant impact on the SNR. In comparison to the known AC, the use of default scatter correction (k = 0.47) or object-specific scatter correction (k = 0.18) resulted in an underestimation of ACrec in the largest sphere volume (26.5 ml) by - 13.9 kBq/ml (- 16.3%) and - 7.1 kBq/ml (- 8.4%), respectively. An increase in total iterations leads to an increase in estimated AC and a decrease in SNR. The mean difference between ACrec and known AC decreased with an increasing number of total iterations (e.g., for 20 iterations (2 iterations/10 subsets) = - 14.6 kBq/ml (- 17.1%), 240 iterations (24i/10s) = - 8.0 kBq/ml (- 9.4%), p < 0.0001). In parallel, the mean SNR decreased significantly from 2i/10s to 24i/10s by 76% (p < 0.0001).ConclusionQuantitative SPECT imaging is feasible with the used reconstruction algorithm and hybrid SPECT/CT, and its consistent implementation in diagnostics may provide perspectives for quantification in routine clinical practice (e.g., assessment of bone metabolism). When combining quantitative analysis and diagnostic imaging, we recommend using two different reconstruction protocols with task-specific optimized setups (quantitative vs. qualitative reconstruction). Furthermore, individual scatter correction significantly improves both quantitative and qualitative results.

Project description:BackgroundQuantitative bone SPECT/CT is useful for disease follow up and inter-patient comparison. For bone metastatic malignant lesions, spine is the most commonly invaded site. However, Quantitative studies with large sample size investigating all the segments of normal cervical, thoracic and lumbar vertebrae are seldom reported. This study was to evaluate the quantitative tomography of normal vertebrae using 99mTc-MDP with SPECT/CT to investigate the feasibility of standardized uptake value (SUV) for differential diagnosis of benign and malignant bone lesions.MethodsA retrospective study was carried out involving 221 patients (116 males and 105 females) who underwent SPECT/CT scan using 99mTc-MDP. The maximum SUV (SUVmax), mean SUV (SUVmean) and CT values (Hounsfield Unit, HU) of 2416 normal vertebrae bodies, 157 benign bone lesions and 118 malignant bone metastasis foci were obtained. The correlations between SUVmax of normal vertebrae and CT values of normal vertebrae, age, height, weight, BMI of patients were analyzed. Statistical analysis was performed with data of normal, benign and malignant groups corresponding to same sites and gender.ResultsThe SUVmax and SUVmean of normal vertebrae in males were markedly higher than those in females (P < 0.0009). The SUVmax of each normal vertebral segment showed a strong negative correlation with CT values in both males and females (r = - 0.89 and - 0.92, respectively; P < 0.0009). The SUVmax of normal vertebrae also showed significant correlation with weight, height, and BMI in males (r = 0.4, P < 0.0009; r = 0.28, P = 0.005; r = 0.22, P = 0.026), and significant correlation with weight and BMI in females (r = 0.32, P = 0.009; r = 0.23, P = 0.031). The SUVmax of normal group, benign bone lesion group and malignant bone metastasis foci group showed statistical differences in both males and females.ConclusionOur study evaluated SUVmax and SUVmean of normal vertebrae, benign bone lesion and malignant bone metastasis foci with a large sample population. Preliminary results proved the potential value of SUVmax in differentiation benign and malignant bone lesions. The results may provide a quantitative reference for clinical diagnosis and the evaluation of therapeutic response in vertebral lesions.

Project description:BackgroundThe relationship between the mean absorbed dose delivered to the tumour and the outcome in liver metastases from colorectal cancer patients treated with radioembolization has already been presented in several studies. The optimization of the personalized therapeutic activity to be administered is still an open challenge. In this context, how well the 99mTc-MAA SPECT/CT predicts the absorbed dose delivered by radioembolization is essential. This work aimed to analyse the differences between predictive 99mTc-MAA-SPECT/CT and post-treatment 90Y-microsphere PET/CT dosimetry at different levels. Dose heterogeneity was compared voxel-to-voxel using the quality-volume histograms, subsequently used to demonstrate how it could be used to identify potential clinical parameters that are responsible for quantitative discrepancies between predictive and post-treatment dosimetry.ResultsWe analysed 130 lesions delineated in twenty-six patients. Dose-volume histograms were computed from predictive and post-treatment dosimetry for all volumes: individual lesion, whole tumoural liver (TL) and non-tumoural liver (NTL). For all dose-volume histograms, the following indices were extracted: D90, D70, D50, Dmean and D20. The results showed mostly no statistical differences between predictive and post-treatment dosimetries across all volumes and for all indices. Notably, the analysis showed no difference in terms of Dmean, confirming the results from previous studies. Quality factors representing the spread of the quality-volume histogram (QVH) curve around 0 (ideal QF = 0) were determined for lesions, TL and NTL. QVHs were classified into good (QF < 0.18), acceptable (0.18 ? QF < 0.3) and poor (QF ? 0.3) correspondence. For lesions and TL, dose- and quality-volume histograms are mostly concordant: 69% of lesions had a QF within good/acceptable categories (40% good) and 65% of TL had a QF within good/acceptable categories (23% good). For NTL, the results showed mixed results with 48% QF within the poor concordance category. Finally, it was demonstrated how QVH analysis could be used to define the parameters that predict the significant differences between predictive and post-treatment dose distributions.ConclusionIt was shown that the use of the QVH is feasible in assessing the predictive value of 99mTc-MAA SPECT/CT dosimetry and in estimating the absorbed dose delivered to liver metastases from colorectal cancer via 90Y-microspheres. QVH analyses could be used in combination with DVH to enhance the predictive value of 99mTc-MAA SPECT/CT dosimetry and to assist personalized activity prescription.

Project description:PurposeSentinel lymph node (SLN) biopsy has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). [99mTc]Tc-tilmanocept may be of benefit in OSCC with complex lymphatic drainage patterns and close spatial relation to SLNs.MethodsA prospective within-patient evaluation study was designed to compare [99mTc]Tc-tilmanocept with [99mTc]Tc-nanocolloid for SLN detection. A total of 20 patients with early-stage OSCC were included, who underwent lymphoscintigraphy with both tracers. Both lymphoscintigraphic images of each patient were evaluated for SLN detection and radiotracer distribution at 2-4 h post-injection.ResultsThe injection site's remaining radioactivity was significantly lower for [99mTc]Tc-tilmanocept (29.9%), compared with [99mTc]Tc-nanocolloid (60.9%; p < 0.001). Radioactive uptake in SLNs was significantly lower for [99mTc]Tc-tilmanocept (1.95%) compared with [99mTc]Tc-nanocolloid (3.16%; p = 0.010). No significant difference was seen in SLN to injection site ratio in radioactivity between [99mTc]Tc-tilmanocept (0.066) and [99mTc]Tc-nanocolloid (0.054; p = 0.232). A median of 3.0 and 2.5 SLNs were identified with [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid, respectively (p = 0.297). Radioactive uptake in higher echelon nodes was not significantly different between [99mTc]Tc-tilmanocept (0.57%) and [99mTc]Tc-nanocolloid (0.86%) (p = 0.052). A median of 2.0 and 2.5 higher echelon nodes was identified with [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid, respectively (p = 0.083).Conclusion[99mTc]Tc-tilmanocept had a higher injection site clearance, but at the same time a lower uptake in the SLN, resulting in an SLN to injection site ratio, which was not significantly different from [99mTc]Tc-nanocolloid. The relatively low-radioactive uptake in SLNs of [99mTc]Tc-tilmanocept may limit intraoperative detection of SLNs, but can be overcome by a higher injection dose.

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A Microdosing Study with 99mTc-PHC-102 for the SPECT/CT Imaging of Primary and Metastatic Lesions in Renal Cell Carcinoma Patients.

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A Microdosing Study with ^99mTc-PHC-102 for the SPECT/CT Imaging of Primary and Metastatic Lesions in Renal Cell Carcinoma Patients.