The impact of measuring split kidney function on post-donation kidney function: A retrospective cohort study
Kelly C. Harper, Jean-Paul Salameh, Natasha Akhlaq, Matthew D. F. McInnes, Victoria Ivankovic, Mahdi H. Beydoun, Edward G. Clark, Wanzhen Zeng, Brian D. M. Blew, Kevin D. Burns, Manish M. Sood, Ann Bugeja
PLOS One. 2021; 16(7): e0253609. DOI: 10.1371/journal.pone.0253609
Background: Living kidney donation requires an extensive evaluation process prior to the donation, a fact which donors have cited as a challenge. The work-up includes abdominopelvic CT for assessment of structural anomalies and for surgical planning, as well as nuclear renography to assess the kidney function in each kidney (split kidney function), with the intent to leave the donor with the higher functioning kidney. Despite this, there is no clear evidence for the predictive value of split kidney function testing on the donors’ long-term remaining kidney function.
Purpose: To determine if CT and/or nuclear renography can predict post-donation kidney function.
Methods: This single-centre retrospective chart review of all living kidney donors between January 2009 and July 2019 looked at each donor’s pre-donation evaluation CT, nuclear renography, eGFR, their post-donation eGFR, and which kidney was donated. CT measurements of the kidneys included craniocaudal dimension, two-dimensional modified ellipsoid volume, and three-dimensional volume.
Nuclear renography was performed with Tc99m-DTPA or Tc99m-MAG3 and determined function at 1-3 minutes. Split renal function by renography was calculated as the function of the right kidney minus that of the left. By CT, it was assumed that function was proportional to size. A significant difference was defined as greater than 10%. Predicted post-donation eGFR was calculated as (pre-donation eGFR)x(%split kidney function of the retained kidney). Pearson’s correlation coefficient was used to determine the correlation between predicted and actual post-donation eGFR. Bland-Altman analysis was used to determine the agreement between split kidney function by CT and by nuclear renography.
Results: 243 of 291 donors’ charts had all required information. The average pre-donation eGFR was 99 mL/min/1.73m2; the average post-donation eGFR was 67 mL/min/1.73m2, with a mean follow-up of 31 months. Significant split kidney function >10% was seen in 26 donors (11%) by renography; in 20 of those donors (70%), this split function was not identified by any CT measurement.
Overall correlation between CT measurements (craniocaudal dimension, two-dimensional modified ellipsoid volume, and three-dimensional volume) of the remaining kidney and the true post-donation eGFR was negligible (R = 0.15, 0.23, and 0.17, respectively), as was the correlation with nuclear renography prediction and true post-donation eGFR (R = 0.24). For those with low post-donation eGFR (<60 mL/min/1.73m2, 40% of donors), CT prediction correlations remained negligible (R = 0.23, 0.25, and 0.25, respectively) while nuclear renography was low (R = 0.35).
Conclusions: Neither CT nor nuclear renography have adequate predictive value of post-donation eGFR, for both high and low eGFR predictions. While both modalities are similar in their post-donation eGFR predictions, nuclear renography is better at identifying significant split renal function than CT, which may be important for some donors’ post-donation kidney function. This, therefore, precludes the use of CT alone in the evaluation of living kidney donation.
Impact of 68Ga-FAPI PET/CT Imaging on the Therapeutic Management of Primary and Recurrent Pancreatic Ductal Adenocarcinomas
Manuel Röhrich, Patrick Naumann, Frederik L. Giesel, Peter L. Choyke, Fabian Staudinger, Annika Wefers, Dawn P. Liew, Clemens Kratochwil, Hendrik Rathke, Jakob Liermann, Klaus Herfarth, Dirk Jäger, Jürgen Debus, Uwe Haberkorn, Matthias Lang, Stefan A. Koerber
Journal of Nuclear Medicine. 2021; 62(6): 779-86. DOI: https://doi.org/10.2967/jnumed.120.253062
Background: Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival of only 10%, which highlights the need for early and accurate staging. 18F-FDG PET has been shown to be sensitive for PDAC but has variable detection of metastatic lymph nodes. In PDAC and many other cancers, cancer-associated fibroblasts are a dominant part of the tumor extracellular matrix, and promote tumor growth, metastasis, and treatment resistance. Unlike on normal fibroblasts, fibroblast activation protein (FAP) is expressed on these cancer-associated fibroblasts, making radiolabelled FAP-inhibitors (FAPI) potential molecules for PET/CT imaging in epithelial tumors such a PDAC.
Purpose: To investigate the utility of 68Ga-labelled FAPI (68Ga-FAPI) PET/CT for PDAC staging compared to contrast-enhanced CT (CE-CT)
Methods: 19 patients with PDAC and inconclusive imaging results were referred by their oncologist to be included in this study. All patients underwent CE-CT, and pre-operative patients also underwent abdominal ultrasonography. 68Ga-FAPI PET/CT imaging was performed an average of 17.6 days after CE-CT, by injecting 167-293 MBq 68Ga-FAPI one hour prior to PET/CT image acquisition to maximize tumor-to-background ratio. 68Ga-FAPI uptake was evaluated by mean (SUVmean) and maximum (SUVmax) standard uptake value in the tumor and in normal organs. The authors noted change in staging, localization of metastases, and treatment plans.
Results: The average tumor SUVmax was 13.37 and SUVmean was 7.32. Preoperative tumors (7 patients) showed higher SUVmax and SUVmean than local recurrences, and higher SUVmax and SUVmean were noted in metastatic lymph nodes and in distance metastases. All normal organs and uninvolved pancreatic tissue showed very low SUVmax and SUVmean. 68Ga-FAPI PET/CT imaging resulted in staging changes in 10 patients due to the detection of additional distant metastases not appreciated on CE-CT; in 2 of these patients, the detection of metastatic lymph nodes which were equivocal on CE-CT also affected the staging and management. 68Ga-FAPI PET/CT imaging resulted in management changes in 7 patients, included major changes for 5 of these patients (for examples, decision to cancel treatment or to treat a single local metastasis).
Conclusions: 68Ga-FAPI was shown to have a strong uptake in PDAC malignant cells compared to normal organs, with implications for management in 7 of the 19 patients studied. The high tumor-to-background ratio exhibited for 68Ga-FAPI PET/CT imaging in this study suggests that this could be a promising new modality for staging PDAC and other epithelial cancers pending larger studies.
Safety of Fibroblast Activation Protein–Targeted Radionuclide Therapy by a Low-Dose Dosimetric Approach Using 177Lu-FAPI04
Serkan Kuyumcu, Bilal Kovan, Yasemin Sanli, Fikret Buyukkaya, Duygu Has Simsek , Zeynep Gözde Özkan, Emine Goknur Isik, Meltem Ekenel, Cuneyt Turkmen
Clinical Nuclear Medicine. 2021; 46(8): 641-6. DOI: 10.1097/RLU.0000000000003667
Background: Radiolabelled fibroblast activation protein inhibitors (FAPI) have shown promising results for PET/CT imaging of cancers with significant cancer-associated fibroblast composition, demonstrating high tumor-to-background ratios. This makes FAPI a candidate for use in both imaging and therapy, theranostics.
Purpose: To investigate the safety of 177Lu-FAPI as a potential therapeutic agent by dosimetry.
Methods: Four otherwise well patients with progressive metastatic advanced-stage disease with no alternate treatment options were selected for this study. Three activity standards of 177Lu-FAPI were used to determine the activity in MBq conveyed per counts on SPECT. 177Lu-FAPI was administered and whole body and abdominopelvic SPECT/CT images were acquired at 4-, 24-, 48-, and 96-hours post-injection. Region/volumes of interest for the tumor, liver, spleen, and renal cortices were drawn on the CT images prior to SPECT/CT reconstruction for use in dosimetry calculation. To investigate bone marrow dosimetry, the authors drew 1-mL blood samples 5-, 15-, 30-, 60-, 90-, and 180-minutes, and 24-, 48-, and 96-hours post-injection of 177Lu-FAPI: total blood activity was used to calculate expected bone marrow activity
Results: The four patients in this study had triple-negative metastatic breast cancer, metastatic thymic carcinoma, metastatic papillary thyroid cancer, and metastatic ovarian carcinosarcoma, all refractory to their treatment options. The patients received between 259 and 278 MBq of 177Lu-FAPI with no adverse effects observed immediately or within a week post-injection.
The mean absorbed dose per MBq of 177Lu-FAPI was highest in the urinary bladder (0.32 mGy) and kidneys (0.25 mGy), and least in the bone marrow (0.04 mGy) and overall total body calculation (0.04 mGy). Tumoral absorption was highest in metastatic bone: the mean absorbed dose per MBq of 177Lu-FAPI in metastatic bone was 0.62 mGy, in metastatic lymph nodes was 0.38 mGy, and in metastatic soft tissue was 0.37 mGy.
Conclusions: In this small proof-of-concept study, the authors show that 177Lu-FAPI has favourable dosimetry in non-target organs but may also show low uptake in tumoral tissue. The mean absorbed dose per MBq of 177Lu-FAPI in the kidneys, thought of as dose-limiting organs, is lower than that for current PSMA and DOTATE therapies; the mean absorbed dose in the bone marrow, the most radiosensitive tissue, is much lower than the safety threshold (2 Gy). The results suggest the safety of 177Lu-FAPI as a potential therapeutic complement to 68Ga-FAPI, but raise questions about the dosing which would be required for efficacy: the average dose absorbed in tumoral tissue was found to be significantly lower than that for PSMA and DOTATE therapies. This could be attributed to the variety of cancers being targeted in this study, and more investigation is needed.
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