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Background  Peptide receptor radionuclide therapy (PRRT) with  177 Lu-[DOTA 0 ,Tyr 3 ]octreotate ( 177 Lu-octreotate) is generally performed using a fixed activity of 7.4 GBq (200 mCi) per course bound to 180 to 300 μg of the peptide. While this single activity may lead to suboptimal radiation doses in neuroendocrine tumors (NET) with advanced or bulky disease, dose escalation has been withheld due to concerns on potential tumor somatostatin receptor saturation with reduced efficacy of the added activity.  In vivo  saturation effects during standard-dose PRRT based on quantification of pre- and intra-therapeutic  68 Ga-DOTATOC positron emission tomography (PET) imaging might guide potential dose escalation.    Methods  Five patients with metastatic NET of the pancreas underwent  68 Ga-DOTATOC PET/CT before and directly after standard-dose PRRT with  177 Lu-octreotate. In each patient, four target tumor lesions, normal liver parenchyma, and the spleen were evaluated and the ratios of SUV max  of the target lesions to liver (SUV T/L ) and spleen (SUV T/S ) were calculated; paired Student's  t  test was performed with  p  < 0.05 for pre-/intra-PRRT comparisons.    Results  The mean intra-therapeutic tumor SUV max  showed no significant change (per-lesion paired  t  test) compared to pretreatment values (-9.1%,  p  = 0.226). In contrast, the SUV max  of the normal liver parenchyma and spleen were significantly lower directly after infusion of 7.4 GBq  177 Lu-octreotate. Consequently, SUV T/L  and SUV T/S  increased significantly from pretreatment to intra-therapeutic examination: SUV T/L  ( p  < 0.001) from 2.8 ± 1.3 (1.3 to 5.8) to 4.7 ± 3.0 (2.1 to 12.7) and SUV T/S  ( p  < 0.001) from 1.2 ± 0.7 (0.4 to 3.0) to 3.5 ± 1.5 (1.6 to 7.9).    Conclusions  This small retrospective study provides preliminary evidence for the absence of relevant  in vivo  saturation of somatostatin receptor subtype 2 (sst2) in tumor lesions during PRRT with standard activities of  177 Lu-octreotate in contrast to normal tissue (liver, spleen) showing limited receptor capacity. After being confirmed by larger series, this observation will have significant implications for PRRT: (1) Higher activities of  177 Lu-octreotate might be considered feasible in patients with high tumor disease burden or clinical need for remission, and (2) striving to reduce the amount of peptide used in standard preparations of  177 Lu-octreotate appears futile.

ejnmmi research

Does PRRT with standard activities of 177Lu-octreotate really achieve relevant somatostatin receptor saturation in target tumor lesions?: insights from intra-therapeutic receptor imaging in patients with metastatic gastroenteropancreatic neuroendocrine tumors