90 Y radioembolization is a promising therapy for patients with primary and secondary liver malignancies. Pretherapeutic assessment consists of hepatic angiography and 99m Tc-macroaggregated albumin ( 99m Tc-MAA) perfusion scintigraphy to estimate the liver-to-lung shunt and exclude extrahepatic 99m Tc-MAA deposition. However, the predictive value of intratumoral 99m Tc-MAA uptake remains unclear. Methods: One hundred four patients with chemotherapy-refractory liver-dominant metastatic colorectal cancer were treated with 90 Y radioembolization between December 2006 and December 2010. All of the patients underwent angiographic assessment and perfusion scintigraphy with 99m Tc-MAA before lobar 90 Y radioembolization. For inclusion, patients must have undergone pretherapeutic and follow-up MR imaging (6 wk and 3 mo after radioembolization, respectively). The degree of intratumoral 99m Tc-MAA uptake was rated, and liver metastases were classified according to changes in tumor diameter on both an individual and a patient basis using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Response at both time points, MAA uptake, and catheter position were then statistically analyzed in a linear and generalized linear mixed model at a significance level of 0.05 (P value). Results: Sixty-six patients with a total of 435 colorectal liver metastases (mean number of lesions 6 SD, 6.6 6 2.8; mean lesion size 6 SD, 33.8 6 21.2 mm; lesion size range, 10-154 mm) were included in this analysis. According to the patient-based analysis, 3 patients had partial response, 49 stable disease, and 6 progressive disease after 6 wk. After 3 mo, 5 patients showed partial response, 26 stable disease, and 17 progressive disease. There was no association of patient-based tumor response with overall 99m Tc-MAA uptake (P 5 0.172) or with catheter position (P 5 0.6456). Furthermore, an interaction effect of 99m Tc-MAA uptake and catheter position in relation to tumor response was not found (P 5 0.512). Moreover, in lesion-based analysis according to RECIST 1.1 there was no association of tumor response with degree of 99m Tc-MAA uptake, catheter position, or interaction of 99m Tc-MAA uptake and catheter position (P 5 0.339, 0.593, and 0.658, respectively). Conclusion: Response to 90 Y radioembolization was found to be independent of the degree of 99m Tc-MAA uptake. Therefore, therapy should not be withheld from patients with colorectal liver metastases lacking intratumoral 99m Tc-MAA accumulation. Radi oembolization with 90 Y is a promising catheterbased liver-directed modality approved by the Food and Drug Administration for the treatment of patients with hepatic metastases of colorectal carcinoma (1-4). For this interventional technique, 90 Y-embedded microspheres of glass or resin are infused directly into the hepatic arteries, where they become lodged within the tumor microvasculature and irradiate the tumor by b-emission (5).Perfusion scintigraphy with 99m Tc-labeled macroaggregated albumin ( 99m Tc-MAA) is mandatory before 90 Y radioem...

Increased expression of neurotensin receptor 1 (NTR1) has been shown in a large number of tumor entities such as pancreatic or colon carcinoma. Hence, this receptor is a promising target for diagnostic imaging and radioligand therapy. Using the favorable biodistribution data of the NTR1-targeting agent In-3BP-227, we investigated the therapeutic effect of itsLu-labeled analog on the tumor growth of NTR1-positive HT29 colon carcinoma xenografts. 3BP-227 was labeled withLu. To assess its biodistribution properties, SPECT and CT scans of HT29-xenografted nude mice injected with Lu-3BP-227 were acquired, and ex vivo tissue activity was determined. To evaluate therapeutic efficacy, 2 groups of mice received the radiopharmaceutical in a median dose of either 165 MBq (129-232 MBq, = 10) or 110 MBq (82-116 MBq, = 10), whereas control mice were injected with vehicle ( = 10). Tumor sizes and body weights were monitored for up to 49 d. Renal function and histologic morphology were evaluated. Whole-body SPECT/CT images allowed clear tumor visualization with low background activity and high tumor-to-kidney and -liver ratios. Ex vivo biodistribution data confirmed high and persistent uptake ofLu-3BP-227 in HT29 tumors (19.0 ± 3.6 vs. 2.7 ± 1.6 percentage injected dose per gram at 3 and 69 h after injection, respectively). The application of Lu-3BP-227 resulted in a distinct delay of tumor growth. Median tumor doubling time for controls was 5.5 d (interquartile range [IQR], 2.8-7.0), compared with 17.5 d (IQR, 5.5-22.5 d) for the 110-MBq and 41.0 d (IQR, 27.5-55.0) for the 165-MBg group. Compared with controls, median relative tumor volume at day 23 after injection was reduced by 55% ( = 0.034) in the 110-MBq and by 88% ( < 0.01) in the 165-MBq group. Renal histology and clinical chemistry results did not differ between radiotherapy groups and controls, suggesting absence of therapy-induced acute renal damage. These data demonstrate that the novel NTR1-targeting theranostic agent 3BP-227 is an effective and promising candidate for radioligand therapy, with a favorable preliminary safety profile and high potential for clinical translation.

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The iPET interpretation using a dedicated PET-based response scale assured a low interobserver variability in per-region but not in per-patient analyses in a multicenter read. Using a sensitive read out (iPET+, score ≥ 3) a reliable identification of patients suffering relapse was limited to those with early relapse.

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