SNMMI 2024: The Tumor Sink Effect on PSMA-PET/CT in Metastatic Prostate Cancer and its Implications for PSMA-RLT: Insight from the 3TMPO Study

(UroToday.com) The Society of Nuclear Medicine & Molecular Imaging (SNMMI) 2024 Annual Meeting held in Toronto, ON between June 8th and June 11th, 2024 was host to a prostate cancer imaging session. Dr. Atefeh Zamanian provided insights from the 3TMPO study evaluating the tumor sink effect on PSMA-PET/CT in metastatic prostate cancer and its implications for PSMA radioligand therapy.


The term ‘sink effect’ was introduced by Beauregard et al. in neuroendocrine tumors and refers to tumor sequestration of radiotracer leading to decreased bioavailability in healthy tissue resulting in lower absorbed radiation dose to critical organs. In PET/CT imaging, the organ uptake values vary considerably among patients with diverse tumor loads.1 This lower uptake may translate into lower healthy tissue irradiation in patients receiving radiopharmaceutical therapy. Instead of a fixed-dose strategy, the injected activity could be adjusted to the existing tumor burden.

The objectives of this study were to investigate the tumor sink effect on PSMA imaging in patients with metastatic castrate-resistant prostate cancer (mCRPC) and to correlate body habitus and renal function with healthy tissue uptake. Ninety-eight patients with progressive mCPRC and at ≥3 metastases on conventional imaging were enrolled in 3TMPO, a prospective multicenter cohort study investigating intra-patient inter-metastatic heterogeneity using multi-tracer PET/CT (NCT04000776). As part of this study, all participants underwent a whole-body PET/CT 60 minutes after injection of 68Ga-PSMA-617. One was excluded because of missing data and therefore 97 participants were included in this analysis.

The total tumor burden was delineated semi-automatically by drawing a volume of interest (VOI) including all voxels with an SUV ≥ 1.5x liver SUVmean followed by removal of sub-VOIs <1cc or representing benign uptake. The total lesion fraction was obtained by dividing the total lesion activity by the body weight in grams and expressed in percent. Participants were stratified into three tumor burden groups: Small (<10%), Moderate (≥10% to <25%) and Large (≥25%) total lesion fraction. Weight, lean body weight (LBW), body surface area (BSA) and estimated glomerular filtration rate (eGFR) were also considered as independent variables. The liver and blood pool (thoracic aorta) activity concentrations were sampled using 3-cm spherical VOIs. For target organs, i.e. the kidneys, parotid glands and spleen, 2-cm VOIs centered on the location of organ SUVpeak were used. All uptake data was expressed in percent injected activity per cc (%IA/cc), which is in principle more directly related to the specific absorbed dose (Gy/GBq) than SUV in a therapeutic setting. Data was analyzed using Spearman correlations and Kruskal-Wallis tests followed by Dunn’s post-hoc tests. 

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The median total lesion fraction was 2.2% (range: 0% to 43.5%). Among the 97 participants, 72 (74%) were found to have a small, 17 (18%) a moderate, and 8 (8%) a large tumor burden. For each healthy tissue, the IA%/cc was negatively and significantly correlated with total lesion fraction (r ranging -0.33 to -0.46; p<0.001), and statistically significant differences in tissues IA%/cc were found between the tumor burden groups (Figure 1; p<0.01).

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The IA%/cc of the liver and blood was also negatively and significantly correlated with weight, LBW, BSA and eGFR (r ranging -0.23 to -0.33; p<0.05), while that of the parotid with weight and BSA (r of -0.27 and -0.23, respectively; p<0.05). When combining predictive variables, the term [BSA/(1-TLF)] tended to yield the strongest negative correlations with healthy tissues IA%/cc (r ranging -0.33 to -0.63; p<0.001).

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Dr. Zamanian concluded that there was a tumor sink effect among mCRPC patients scanned with 68Ga-PSMA-617 PET/CT. This finding supports that, in the context of PSMA radioligand therapy, patients with a larger tumor burden are likely to receive lower absorbed doses to healthy tissues than they could have theoretically tolerated and, as such, be undertreated with the current one-size-fits-all, fixed-activity regimes. Other factors such as body habitus and renal function may predictably further impact the biodistribution of PSMA radioligands and consequently the dosimetry during PSMA radioligand therapy. Personalizing PSMA radioligand therapy could allow clinicians to safely increase the injected activity, tumor absorbed dose and clinical benefits in a substantial proportion of patients, and particularly those with a larger tumor burden who stand to benefit from this treatment intensification. 

Presented by: Atefeh Zamanian, PhD, Radiation Biologist, Division of Oncology, Cancer Research Center of CHU de Quebec-Laval University, Quebec City, QC 

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, May 31 – Tues, June 4, 2024. 

References:

  1. Beauregard JM, Hofman MS, Kong G, Hicks R. The tumour sink effect on the biodistribution of 68Ga-DOTA-octreotate: implications for peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging. 2012;39(1): 50-6.