RESUMO
177Lu-iPSMA is a novel radioligand developed at ININ-Mexico with a high affinity for the PSMA protein heavily expressed in cancer cells of approximately 95% of patients with metastatic castration-resistant prostate cancer (mCRPC). 177Lu-DOTATOC is a patent-free radioligand, molecularly recognized by somatostatin receptors (SSTR-2) overexpressed in cancer cells of about 80% of patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET). This translational research aimed to determine the efficacy and safety of 177Lu-iPSMA and 177Lu-DOTATOC developed as GMP pharmaceutical formulations for treating progressive and advanced mCRPC and NET. One hundred and forty-five patients with mCRPC and one hundred and eighty-seven subjects with progressive NET (83% GEP-NET and 17% other NET), treated with 177Lu-iPSMA and 177Lu-DOTATOC, respectively, were evaluated. Patients received a mean dose of 7.4 GBq per administration of 177Lu-iPSMA (range 1-5 administrations; 394 treatment doses) or 177Lu-DOTATOC (range 2-8 administrations; 511 treatment doses) at intervals of 1.5-2.5 months. Efficacy was assessed by SPECT/CT or PET/CT. Results were stratified by primary tumor origin and number of doses administered. Patients with mCRPC showed overall survival (OS) of 21.7 months with decreased radiotracer tumor uptake (SUV) and PSA level in 80% and 73% of patients, respectively. In addition, a significant reduction in pain (numerical scale from 10-7 to 3-1) was observed in 88% of patients with bone metastases between one and two weeks after the second injection. In the GEP-NET population, the median progression-free survival was 34.7 months, with an OS of >44.2 months. The treatments were well tolerated. Only ten patients experienced grade ≥ 3 myelosuppression (3% of all patients). The observed safety profiles and favorable therapeutic responses demonstrated the potential of 177Lu-iPSMA and 177Lu-DOTATOC to improve overall survival and quality of life in patients with progressive and advanced mCRPC and NET.
RESUMO
Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) has found widespread use for the diagnosis of biochemical recurrence of prostate cancer (PCa). Unfortunately, PET/CT is not as widely available; thus a PSMA-targeting compound for scintigraphy is of special interest. The aim of this study was to compare 99mTc-EDDA/HYNIC-iPSMA and 68Ga-PSMA-11 PET/CT qualitatively and semi-quantitatively. Twenty-three patients with metastatic PCa were underwent 99mTc-EDDA/HYNIC-iPSMA SPECT/CT followed by 68Ga-PSMA-11 PET/CT. Gleason score in all patients was obtained. Maximal standardized uptake value (SUVmax) and counts per organ, including the primary and metastatic tumor, were normalized and compared using Pearson's correlation test. Sites considered as positive have increased SUVmax and tumor-to-background ratio (TBR) in comparison with non-diseased organs/tissues (SUVmax =25.2±4.7, 18.4±1.6, 11.4±1.2 (P=0.037) from prostate, bone and lymph nodes versus TBR =35.9±45.2, 15.4±18.9, 19.1±51.7 (P=0.035) for prostate, bone and lymph nodes. 99mTc-HYNIC-iPSMA and 68Ga-PSMA-11 uptake values in the evaluation of the affected nodes were very similar, although their ranges ranged from 5-21 mm (12±7.6). Correlation coefficient was normalized between SUVmax and TBR, demonstrating r values for prostate of r2=0.731; for bone of r2=0.720; and lymph nodes of r2=0.864 (P<0.05 in all cases). Values and confidence interval at the 95% are supporting the equivalency of both parameters in primary tumor and metastases (prostate 95% CI=4.61, 4.38; bone tissue 95% CI=-2.21, 3.41 and lymph node 95% CI=4.67). We conclude that 68Ga-PSMA-11 PET/CT and 99mTc-EDDA/HYNIC-iPSMA SPECT/CT were comparable, supporting the use of 99mTc-EDDA/HYNIC-iPSMA in patients with progressive metastatic castration-resistant PCa.