Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) induces a rapid and extensive increase in liver volume. The functional quality of this hypertrophic response has ...been called into question because ALPPS is associated with a substantial incidence of liver failure and high perioperative mortality. This multicenter study aimed to evaluate functional liver regeneration in contrast to volumetric liver regeneration in ALPPS, using technetium-99m hepatobiliary scintigraphy and computed tomography volumetry, respectively.
Patients who underwent ALPPS and hepatobiliary scintigraphy in 6 centers were included. Hepatobiliary scintigraphy data were analyzed centrally at the Academic Medical Center in Amsterdam according to established protocols. Increase in liver function as measured by hepatobiliary scintigraphy after stage 1 of ALPPS was compared with the increase in liver volume. In addition, we analyzed the impact of liver function and volume on postoperative outcomes including liver failure, morbidity, and mortality.
In 60 patients, future liver remnant volume increased by a median 78% (interquartile range 48–110) during a median 8 (interquartile range 6–14) days after stage 1, while function as measured by hepatobiliary scintigraphy increased by a median 29% (interquartile range 1–55) throughout 7 days (interquartile range 6–10) in the 27 patients with paired measurements. After stage 2 of ALPPS, liver failure occurred in 5/60 (8%) patients, severe complications in 24/60 (40%), and mortality occurred in 4/60 (7%).
In ALPPS, volumetry overestimates liver function as measured by hepatobiliary scintigraphy and may be responsible for the high rate of liver failure. Quantitative liver function tests are highly recommended to avoid post hepatectomy liver failure.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background
Despite a fast and potent growth of the future liver remnant (FLR), patients operated with associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) are at risk ...of developing posthepatectomy liver failure. In this study, the relation between liver volume and function in ALPPS was studied using a multimodal assessment.
Methods
Nine patients with colorectal liver metastases treated with neoadjuvant chemotherapy and operated with ALPPS were studied with hepatobiliary scintigraphy, computed tomography, indocyanine green clearance test, and serum liver function tests. A comparison between liver volume and function was conducted.
Results
The preoperative FLR volume of 19.5% underestimated the preoperative FLR function of 25.3% (
p
= 0.011). The increase in FLR volume exceeded the increase in function at day 6 after stage 1 (FLR volume increase 56.7% versus FLR function increase 28.2%,
p
= 0.021), meaning that the increase in function was 50% of the increase in volume. After stage 2, functional increase exceeded the volume increase, resulting in similar values 28 days after stage 2.
Conclusions
In the inter-stage period of ALPPS, the high volume increase is not paralleled by a corresponding functional increase. This may in part explain the high morbidity and mortality rates associated with ALPPS. Functional assessment of the FLR is advised.
Full text
Available for:
EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
By using solid targets in medical cyclotrons, it is possible to produce large amounts of 68GaCl3. Purification of Ga3+ from metal ion impurities is a critical step, as these metals compete with Ga3+ ...in the complexation with different chelators, which negatively affects the radiolabeling yields. In this work, we significantly lowered the level of iron (Fe) impurities by adding ascorbate in the purification, and the resulting 68GaCl3could be utilized for high-yield radiolabeling of clinically relevant DOTA-based tracers. 68GaCl3 was cyclotron-produced and purified with ascorbate added in the wash solutions through the UTEVA resins. The 68Ga eluate was analyzed for radionuclidic purity (RNP) by gamma spectroscopy, metal content by ICP-MS, and by titrations with the chelators DOTA, NOTA, and HBED. The 68GaCl3eluate was utilized for GMP-radiolabeling of the DOTA-based tracers DOTATOC and FAPI-46 using an automated synthesis module. DOTA chelator titrations gave an apparent molar activity (AMA) of 491 ± 204 GBq/µmol. GMP-compliant syntheses yielded up to 7 GBq/batch 68GaGa-DOTATOC and 68GaGa-FAPI-46 (radiochemical yield, RCY ~ 60%, corresponding to ten times higher compared to generator-based productions). Full quality control (QC) of 68Ga-labelled tracers showed radiochemically pure and stable products at least four hours from end-of-synthesis.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Expanding therapeutic possibilities have improved disease-related prospects for breast cancer patients. Pathological analysis on a tumor biopsy is the current reference standard biomarker ...used to select for treatment with targeted anticancer drugs. This method has, however, several limitations, related to intra- and intertumoral as well as spatial heterogeneity in receptor expression as well as the need to perform invasive procedures that are not always technically feasible.
Main body
In this narrative review, we focus on the current role of molecular imaging with contemporary radiotracers for positron emission tomography (PET) in breast cancer. We provide an overview of diagnostic radiotracers that represent treatment targets, such as programmed death ligand 1, human epidermal growth factor receptor 2, polyadenosine diphosphate-ribose polymerase and estrogen receptor, and discuss developments in therapeutic radionuclides for breast cancer management.
Conclusion
Imaging of treatment targets with PET tracers may provide a more reliable precision medicine tool to find the right treatment for the right patient at the right time. In addition to visualization of the target of treatment, theranostic trials with alpha- or beta-emitting isotopes provide a future treatment option for patients with metastatic breast cancer.
Selective administration of mesenchymal stromal cells to the mesenteric arteries is a potential technique to overcome pulmonary trapping and increase the density of transplanted cells in extensive ...mural inflammation of the intestine, such as in inflammatory bowel disease and graft-versus-host disease. We injected 5 × 106 111In-oxine-labeled human decidual stromal cells (DSCs) to the rabbit superior mesenteric artery (SMA) using clinical routine catheters guided by an angiographical system under sterile conditions. We used longitudinal single-photon emission tomography at 6 h and at 1, 2, and 5 days to assess trafficking and distribution of DSCs. We used digital subtraction angiography, computed tomography, and hematoxylin and eosin stainings to determine biodistribution of cells and to assess safety end points. We found that selective injection of human DSCs to the rabbit SMA does not result in acute embolic complications. Furthermore, we found that IV administration resulted in extensive retention of the radiolabeled DSCs in the lungs, corroborating previous studies on pulmonary trapping. In sharp contrast, selective injections to the SMA resulted in uptake distributed in the intestine supplied by the SMA and in the liver, indicating that this approach could significantly increase the fraction of injected DSCs reaching the target tissue.
Lymphoscintigraphy is an imaging technique to diagnose and characterize the severity of edema in the upper and lower extremities. In lymphoscintigraphy, a scoring system can increase the ability to ...differentiate between diagnoses, but the use of any scoring system requires sufficient reliability. Our aim was to determine the inter- and intraobserver reliability of a proposed scoring system for visual interpretation of lymphoscintigrams of the lower extremities.
The lymphoscintigrams of 81 persons were randomly selected from our database for retrospective evaluation. Two nuclear medicine physicians scored these scans according to the 8 criteria of a proposed scoring system for visual interpretation of lymphoscintigrams of the lower extremities. Each scan was scored twice 3 mo apart. The total score was the sum of the scores for all criteria, with a potential range of 0 (normal lymphatic drainage) to 58 (severe lymphatic impairment). The intra- and interobserver reliability of the scoring system was determined using the Wilcoxon signed-rank test, percentage of agreement, weighted κ, and intraclass correlation coefficient with 95% confidence interval. In addition, for 7 categories, differences in total scores between and within observers were determined.
We found some insignificant differences between observers. Percentage agreement was high or very high, at 82.7%-99.4% between observers and 84.6%-99.4% within observers. For each criterion of the scoring system, the κ-correlations showed moderate to very good inter- or intraobserver reliability. The total scores for all criteria had good inter- and intraobserver reliability. Regarding the interobserver comparison, 66% and 64% of the difference in total scores were within ±1 scale point (-1, +1), and regarding the intraobserver comparison, 68% and 72% of the difference in total scores were within ±1 scale point.
The proposed scoring system is a reliable tool for visual qualitative evaluation of lymph transport problems in patients with lymphedema of the lower extremities.
Human epidermal growth factor receptor 2 (HER2) is a major prognostic and predictive marker overexpressed in 15-20% of breast cancers. The diagnostic reference standard for selecting patients for ...HER2-targeted therapy is based on the analysis of tumor biopsies. Previously patients were defined as HER2-positive or -negative; however, with the approval of novel treatment options, specifically the antibody-drug conjugate trastuzumab deruxtecan, many breast cancer patients with tumors expressing low levels of HER2 have become eligible for HER2-targeted therapy. Such patients will need to be reliably identified by suitable diagnostic methods. Biopsy-based diagnostics are invasive, and repeat biopsies are not always feasible. They cannot visualize the heterogeneity of HER2 expression, leading to a substantial number of misdiagnosed patients. An alternative and highly accurate diagnostic method is molecular imaging with radiotracers. In the case of HER2, various studies demonstrate the clinical utility and feasibility of such approaches. Radiotracers based on Affibody
molecules, small, engineered affinity proteins with a size of ~6.5 kDa, are clinically validated molecules with favorable characteristics for imaging. In this article, we summarize the HER2-targeted therapeutic landscape, describe our experience with imaging diagnostics for HER2, and review the currently available clinical data on HER2-Affibody-based molecular imaging as a novel diagnostic tool in breast cancer and beyond.
In prostate cancer, the early detection of distant spread has been shown to be of importance. Prostate-specific membrane antigen (PSMA)-binding radionuclides in positron emission tomography (PET) is ...a promising method for precise disease staging. PET diagnostics depend on image reconstruction techniques, and ordered subset expectation maximization (OSEM) is the established standard. Block sequential regularized expectation maximization (BSREM) is a more recent reconstruction algorithm and may produce fewer equivocal findings and better lesion detection. Methods: 68Ga PSMA-11 PET/CT scans of patients with de novo or suspected recurrent prostate cancer were retrospectively reformatted using both the OSEM and BSREM algorithms. The lesions were counted and categorized by three radiologists. The intra-class correlation (ICC) and Cohen’s kappa for the inter-rater reliability were calculated. Results: Sixty-one patients were reviewed. BSREM identified slightly fewer lesions overall and fewer equivocal findings. ICC was excellent with regards to definitive lymph nodes and bone metastasis identification and poor with regards to equivocal metastasis irrespective of the reconstruction algorithm. The median Cohen’s kappa were 0.66, 0.74, 0.61 and 0.43 for OSEM and 0.61, 0.63, 0.66 and 0.53 for BSREM, with respect to the tumor, local lymph nodes, metastatic lymph nodes and bone metastasis detection, respectively. Conclusions: BSREM in the setting of 68Ga PMSA PET staging or restaging is comparable to OSEM.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
The Affibody molecule, ABY-025, has demonstrated utility to detect human epidermal growth factor receptor 2 (HER2) in vivo, either radiolabelled with indium-111 (
111
In) or gallium-68 (
...68
Ga). Using the latter,
68
Ga, is preferred due to its use in positron emission tomography with superior resolution and quantifying capabilities in the clinical setting compared to
111
In. For an ongoing phase II study (NCT05619016) evaluating ABY-025 for detecting HER2-low lesions and selection of patients for HER2-targeted treatment, the aim was to optimize an automated and cGMP-compliant radiosynthesis of
68
GaGa-ABY-025.
68
GaGa-ABY-025 was produced on a synthesis module, Modular-Lab PharmTracer (Eckert & Ziegler), commonly used for
68
Ga-labelings. The radiotracer has previously been radiolabeled on this module, but to streamline the production, the method was optimized. Steps requiring manual interactions to the radiolabeling procedure were minimized including a convenient and automated pre-concentration of the
68
Ga-eluate and a simplified automated final formulation procedure. Every part of the radiopharmaceutical production was carefully developed to gain robustness and to avoid any operator bound variations to the manufacturing. The optimized production method was successfully applied for
68
Ga-labeling of another radiotracer, verifying its versatility as a universal and robust method for radiosynthesis of Affibody-based peptides.
Results
A simplified and optimized automated cGMP-compliant radiosynthesis method of
68
GaGa-ABY-025 was developed. With a decay corrected radiochemical yield of 44 ± 2%, a radiochemical purity (RCP) of 98 ± 1%, and with an RCP stability of 98 ± 1% at 2 h after production, the method was found highly reproducible. The production method also showed comparable results when implemented for radiolabeling another similar peptide.
Conclusion
The improvements made for the radiosynthesis of
68
GaGa-ABY-025, including introducing a pre-concentration of the
68
Ga-eluate, aimed to utilize the full potential of the
68
Ge/
68
Ga generator radioactivity output, thereby reducing radioactivity wastage. Furthermore, reducing the number of manually performed preparative steps prior to the radiosynthesis, not only minimized the risk of potential human/operator errors but also enhanced the process’ robustness. The successful application of this optimized radiosynthesis method to another similar peptide underscores its versatility, suggesting that our method can be adopted for
68
Ga-labeling radiotracers based on Affibody molecules in general.
Trial registration
: NCT, NCT05619016, Registered 7 November 2022,
https://clinicaltrials.gov/study/NCT05619016?term=HER2&cond=ABY025&rank=1
In current best practise, curatively intended treatment for oesophageal cancer usually consists of neoadjuvant chemo-radiotherapy (nCRT) or perioperative chemotherapy, and oesophagectomy. Sentinel ...Lymph Node Biopsy (SLNB) has the potential to identify patients without lymph node metastases and thus improve the staging accuracy and influence treatment. The impact of neoadjuvant treatment on the lymphatic drainage of oesophageal cancers and subsequently the SLNB procedure in this tumour type has previously not been well studied.
To evaluate changes in lymphatic drainage patterns of the tumour in patients with cancer of the oesophagus or gastro-oesophageal junction (GOJ) using Sentinel Lymph Node (SLN) hybrid SPECT/CT lymphoscintigraphy before and after nCRT.
Patients with clinical stage T2-T3, any N-stage, M0 cancer of the oesophagus or GOJ underwent endoscopically guided peri-/intratumoral injection of radio-colloid followed by hybrid SPECT/CT lymphoscintigraphy prior to, and once again following, nCRT. SPECT/CT images were evaluated to number and location of SLNs and compared between the two examinations.
Ten patients were included in this pilot trial. SPECT/CT lymphoscintigraphy was performed in twenty procedures. The same Sentinel Lymph Node station before and after nCRT was observed in one single patient. In two patients, no SLN was detected before nCRT. In three patients no SLN was detected following nCRT. In four patients, the SLN stations were not the same station at baseline compared to follow-up examination.
The reproducibility SLN detection in patients with cancer of the oesophagus/GOJ following nCRT was very poor. nCRT appears to alter lymphatic drainage patterns and thus may affect detection of SLNs and potentially also the accuracy of an SLNB in these patients. On the basis of these initial results, we abort further patient recruitment in our institution.
Australian New Zealand Clinical Trials Registry (ANZCTR). Identifier ACTRN12618001433291 . Date registered: 27/08/2018. Retrospectively registered.
PDF
