Fluorine-18-fluorocholine PET/CT parameters predictive for hematological toxicity to radium-223 therapy in castrate-resistant prostate cancer patients with bone metastases

Abstract

PurposeThis study aims to predict hematological toxicity induced by 223Ra therapy. We investigated the value of metabolically active bone tumor volume (MBTV) and total bone lesion activity (TLA) calculated on pretreatment fluorine-18-fluorocholine (18F-FCH) PET/CT in castrate-resistant prostate cancer (CRPC) patients with bone metastases treated with 223Ra radionuclide therapy.Patients and methods18F-FCH PET/CT imaging was performed in 15 patients with CRPC before treatment with 223Ra. Bone metastatic disease was quantified on the basis of the maximum standardized uptake value (SUV), total lesion activity (TLA=MBTV×SUVmean), or MBTV/height (MBTV/H) and TLA/H. 18F-FCH PET/CT bone tumor burden and activity were analyzed to identify which parameters could predict hematological toxicity [on hemoglobin (Hb), platelets (PLTs), and lymphocytes] while on 223Ra therapy. Pearson’s correlation was used to identify the correlations between age, prostate-specific antigen, and 18F-FCH PET parameters.ResultsMBTV ranged from 75 to 1259 cm3 (median: 392 cm3). TLA ranged from 342 to 7198 cm3 (median: 1853 cm3). Patients benefited from two to six cycles of 223Ra (n=56 cycles in total). At the end of 223Ra therapy, five of the 15 (33%) patients presented grade 2/3 toxicity on Hb and lymphocytes, whereas three of the 15 (20%) patients presented grade 2/3 PLT toxicity.Age was correlated negatively with both MBTV (r=−0.612, P=0.015) and TLA (r=−0.596, P=0.018). TLA, TLA/H, and MBTV/H predicted hematological toxicity on Hb, whereas TLA/H and MBTV/H predicted toxicity on PLTs at the end of 223Ra cycles. Receiver operating characteristic curve analysis allowed to define the cutoffs for MBTV (915 cm3) and TLA (4198 cm3) predictive for PLT toxicity, with an accuracy of 0.92 and 0.99.ConclusionTumor bone burden calculation is feasible with 18F-FCH PET/CT with freely available open-source software. In this pilot study, baseline 18F-FCH PET/CT markers (TLA, MBTV) have shown abilities to predict Hb and PLT toxicity after 223Ra therapy and could be explored for patient selection and treatment optimization.

Bone metastasis: mechanisms, therapies, and biomarkers

“…In addition, the cell membrane phospholipid choline can be abnormally metabolized and internalized in tumor cells overexpressing choline kinase (352). This abnormal regulation of the phospholipid metabolism has been observed in situ in cancer cells metastatic to bone (290,348), as visualized by FCH-PET scanning of prostate cancer bone metastases (Figure 8). Autophagy could be another potential source of energy for tumor cells in bone (233).…”

Targeted Radionuclide Therapy: New Advances for Improvement of Patient Management and Response

“…Pre-treatment PET imaging has served as a primary research focus to identify patients who would benefit from or fail therapies with various radionuclide and targeting moiety combinations. For example, Vija et al demonstrated that quantification of bone tumoural burden using 18F-Fluoromethylcholine ( 18 F-FCH) PET/CT could predict normal tissue toxicity, specifically grade 2–3 haematological toxicity after 223 Ra therapy [1]. For tumour response, Murray et al showed that if the response is defined as a change of >21% in the mean standard uptake value (SUV mean ) of bone lesions, the percentage change of 18 F-fluoride PET SUV mean relative to baseline could identify non-responding bone lesions prior to 223 Ra therapy (r 2 = 0.77) [2].…”

The increasing potential of nuclear medicine imaging for the evaluation and reduction of normal tissue toxicity from radiation treatments

“…These tracers do not actively target haematological cells, but the circulation phase and accumulation in normal bone or bone metastases can result in significant dose to bone marrow [41]. A study used baseline [ 18 F]fluorocholine(FCH) PET, typically used to detect metastatic recurrent prostate cancer, to determine bone tumour infiltration and was thereby able to predict haematological toxicity in metastatic prostate cancer patients who received 223 Ra therapy [42]. Imaging the normal tissue directly with [ 18 F]FLT-PET could possibly be used to evaluate toxicity in these cases as well.…”