Tumor Response Assessment to Treatment with [¹⁷⁷Lu-DOTA⁰,Tyr³]Octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors: Differential Response of Bone Versus Soft-Tissue Lesions

Abstract

We have noted that bone lesions on CT respond differently from soft-tissue lesions to treatment with [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate ( 177 Lu-octreotate). We therefore compared the response of bone lesions with that of soft-tissue lesions to treatment with 177 Luoctreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors (NETs). Methods: Forty-two patients with well-differentiated NETs who had bone metastases that were positive on [ 111 In-DTPA 0 ]octreotide somatostatin receptor scintigraphy (SRS) before treatment, and who had soft-tissue lesions, were studied. All patients had had a minimum of 1 follow-up CT scan. Lesions were scored on CT and bone lesions also on SRS before and after treatment. Tumor markers (chromogranin A and 5-hydroxyindoleacetic acid) before and after treatment were compared. Results: Because bone lesions were not visible on CT before treatment in 11 of 42 patients (26%), bone and softtissue lesions were evaluated in 31 patients. Whereas bone lesions increased in size, soft-tissue lesions decreased in size. The percentage change in bone and soft-tissue lesions was significantly different at all time points up to 12 mo of follow-up (P , 0.001). The intensity or number of bone lesions on SRS decreased after treatment in 19 of 23 patients (83%) in whom SRS after treatment was available. The tumor markers also decreased significantly after treatment. In 1 patient, bone lesions became visible on CT after treatment, mimicking progressive disease with "new" bone lesions, although there was an overall treatment response. Conclusion: In patients with NETs, the apparent increase in size of bone lesions or the appearance of new bone lesions on CT after treatment with 177 Lu-octreotate should be interpreted cautiously, as this finding may be therapy-related rather than indicative of tumor progression.

Somatostatin Receptor–Targeted Radiopeptide Therapy with 90Y-DOTATOC and 177Lu-DOTATOC in Progressive Meningioma: Long-Term Results of a Phase II Clinical Trial

“…Somatostatin-based radiopeptide therapy with 90 Y-DOTATOC and 177 Lu-DOTATOC has an established value for treating patients with neuroendocrine tumors (17,(19)(20)(21). On the basis of the current results, DOTATOC is a relatively safe treatment option that should be considered for patients with progressive nonoperable meningiomas who have failed all other treatment options.…”

Evaluation of DOTA-chelated neurotensin analogs with spacer-enhanced biological performance for neurotensin-receptor-1-positive tumor targeting

“…In recent years, 177 Lu, a theranostic radioisotope, has received increasing attention for potential clinical applications due to its dual emission characteristics[24–27]. Upon decay, 177 Lu emits therapeutic beta particles (E avg = 133 keV) and gamma rays (113 and 210 keV, 6% and 10%) that are suitable for SPECT diagnostic imaging.…”

“…Unfortunately, DTPA forms a complex with 177 Lu that in known to be unstable in vivo [31]. Conversely, DOTA, due to its cyclic nature and steric inhibition, is known to form in vivo stable 177 Lu complexes, as demonstrated by numerous preclinical and clinical studies[24,27,31]. At the same time, DOTA, when placed too closely to the pharmacophore, has been shown to sterically inhibit the efficacy of receptor-targeted peptides[17,32].…”

Production of 177Lu for Targeted Radionuclide Therapy: Available Options

“…The in vivo applications of key 177 Lu radiopharmaceuticals for a variety of therapeutic procedures include peptide receptor radionuclide therapy [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26], bone pain palliation [27][28][29][30][31][32][33], radiation synovectomy [34][35][36][37][38][39] and radioimmonutherapy [40][41][42][43][44][45][46]. There is a steadily expanding list of 177 Lu-labeled radiopharmaceuticals that is currently being evaluated at the preclinical research or at product development stages; these may potentially be used in vivo in humans for evaluation for radionuclide therapy [1][2][3].…”