Impact of Tumor Burden on Normal Organ Distribution in Patients Imaged with CXCR4-Targeted [68Ga]Ga-PentixaFor PET/CT

Abstract

Background CXCR4-directed positron emission tomography/computed tomography (PET/CT) has been used as a diagnostic tool in patients with solid tumors. We aimed to determine a potential correlation between tumor burden and radiotracer accumulation in normal organs. Methods Ninety patients with histologically proven solid cancers underwent CXCR4-targeted [68Ga]Ga-PentixaFor PET/CT. Volumes of interest (VOIs) were placed in normal organs (heart, liver, spleen, bone marrow, and kidneys) and tumor lesions. Mean standardized uptake values (SUVmean) for normal organs were determined. For CXCR4-positive tumor burden, maximum SUV (SUVmax), tumor volume (TV), and fractional tumor activity (FTA, defined as SUVmean x TV), were calculated. We used a Spearman's rank correlation coefficient (ρ) to derive correlative indices between normal organ uptake and tumor burden. Results Median SUVmean in unaffected organs was 5.2 for the spleen (range, 2.44 – 10.55), 3.27 for the kidneys (range, 1.52 – 17.4), followed by bone marrow (1.76, range, 0.84 – 3.98), heart (1.66, range, 0.88 – 2.89), and liver (1.28, range, 0.73 – 2.45). No significant correlation between SUVmax in tumor lesions (ρ ≤ 0.189, P ≥ 0.07), TV (ρ ≥ -0.204, P ≥ 0.06) or FTA (ρ ≥ -0.142, P ≥ 0.18) with the investigated organs was found. Conclusions In patients with solid tumors imaged with [68Ga]Ga-PentixaFor PET/CT, no relevant tumor sink effect was noted. This observation may be of relevance for therapies with radioactive and non-radioactive CXCR4-directed drugs, as with increasing tumor burden, the dose to normal organs may remain unchanged.

Associations between Normal Organs and Tumor Burden in Patients Imaged with Fibroblast Activation Protein Inhibitor-Directed Positron Emission Tomography

“…We assessed PET, CT, and hybrid PET/CT overlay for every scan. [ 68 Ga]Ga-FAPI-04 biodistribution in normal organs was determined by placing respective volumes of interest (VOIs) as described in [ 9 , 18 , 19 , 20 ]. This approach allowed us to include a total of 10 VOIs per patient in the liver, spleen, pancreas, left and right kidney, the left myocardial septal wall and lateral wall, and in the vertebral bodies of C2, Th7 and L5.…”

“…To evaluate radiotracer uptake in the heart and in the bone marrow, the average of the respective VOIs was used. Mean standardized uptake values (SUV mean ) were then recorded for normal organs [ 18 , 19 , 20 ]. Total tumor burden was also quantified by drawing spherical volumes of interests.…”

“…Total tumor burden was also quantified by drawing spherical volumes of interests. The software automatically adapted a three-dimensional VOI at a 40% isocontour and averaged maximum standardized uptake values (SUV max ; averaged over all tumor lesions per scan), sum of tumor volume (TV, in cm 3 ), and sum of fractional tumor activity (FTA = TV × SUV mean ) were recorded [ 18 , 19 , 20 ]. Tracer uptake in post-surgical areas was quantified in a similar manner, and SUV max (averaged over all areas showing increased post-surgical uptake per scan), sum of post-surgical FAP-uptake volume (PS-FV in cm 3 per scan), and sum of post-surgical fractional FAP-activity (PS − FFA = PS − FV × SUV mean ; per scan) were recorded.…”

“…Other applications include “cold” FAP-directed drugs, as relevant off-target effects may be reduced in individuals with high tumor load [ 13 ]. While some studies have shown that other PET agents also used in a theranostic setting may be susceptible to such effects of tumor burden on radiotracer uptake in normal organs [ 14 , 15 , 16 , 17 ], other studies have demonstrated either no such effect, or only minimal impact of PET-avid tumor load [ 18 , 19 , 20 ]. Thus, results from previous studies cannot be extrapolated to FAP-directed molecular imaging.…”

Current Status of 68Ga-Pentixafor in Solid Tumours

“…The normal biodistribution of 68 Ga-Pentixafor includes the spleen, kidneys, bone marrow, heart and the liver, which results in undesired tracer accumulation during 177 Lu- and 90 Y-Pentixather therapy leading to adverse effects [ 24 , 25 ]. The tumour sink effect, which is characterized by lower tracer accumulation in the normal organs of patients with high tumour burden, has been demonstrated with therapies targeting PSMA and SSTR in prostate cancer and well-differentiated neuroendocrine tumours, respectively [ 26 ].…”