Initial Clinical Results of a Novel Immuno-PET Theranostic Probe in Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

This prospective study evaluated the imaging performance of a novel pretargeting immunologic PET (immuno-PET) method in patients with human epidermal growth factor receptor 2 (HER2)-negative, carcinoembryonic antigen (CEA)-positive metastatic breast cancer, compared with CT, bone MRI, and 18F-FDG PET. Methods: Twenty-three patients underwent whole-body immuno-PET after injection of 150 MBq of 68Ga-IMP288, a histamine-succinyl-glycine peptide given after initial targeting of a trivalent anti-CEA, bispecific, antipeptide antibody. The gold standards were histology and imaging follow-up. Tumor SUVs (SUVmax and SUVmean) were measured, and tumor burden was analyzed using total tumor volume and total lesion activity. Results: The total lesion sensitivity of immuno-PET and 18F-FDG PET were 94.7% (1,116/1,178) and 89.6% (1,056/1,178), respectively. Immuno-PET had a somewhat higher sensitivity than CT or 18F-FDG PET in lymph nodes (92.4% vs. 69.7% and 89.4%, respectively) and liver metastases (97.3% vs. 92.1% and 94.8%, respectively), whereas sensitivity was lower for lung metastases (48.3% vs. 100% and 75.9%, respectively). Immuno-PET showed higher sensitivity than MRI or 18F-FDG PET for bone lesions (95.8% vs. 90.7% and 89.3%, respectively). In contrast to 18F-FDG PET, immuno-PET disclosed brain metastases. Despite equivalent tumor SUVmax, SUVmean, and total tumor volume, total lesion activity was significantly higher with immuno-PET than with 18F-FDG PET (P = 0.009). Conclusion: Immuno-PET using anti-CEA/anti-IMP288 bispecific antibody, followed by 68Ga-IMP288, is a potentially sensitive theranostic imaging method for HER2-negative, CEA-positive metastatic breast cancer patients and warrants further research.

Preliminary results of a 68 Ga-PSMA PET/CT prospective study in prostate cancer patients with occult recurrence: Diagnostic performance and impact on therapeutic decision-making.

BACKGROUND: In this prospective study (NCT03443609), we investigated the impact of 68Ga-PSMA-11 PET-CT on the treatment plan and therapeutic response obtained for patients with prostate cancer (PCa) presenting a recurrence with a low rising PSA. METHODS: One hundred thirty hormone-naive (PSA < 1.5 ng/mL) patients were enrolled. All patients received radical treatment. PET images were recorded 1 and 2 hours after injection of tracer and interpreted by two independent nuclear physicians. Six months after treatment ended, a PSA assay was requested to evaluate the therapeutic efficacy of the treatment based on PSMA results. RESULTS: Data analysis for the first 52 included patients has been completed. 68Ga-PSMA-11-positive lesions were detected in 38/52 (73.1%) patients. Ninety-four lesions were detected as follows, 53/94 in lymph nodes (56.4%), 25/94 in bone (26.6%), and 12/94 into the prostate bed (12.7%). Detection rates were 58%, 81%, and 82% for serum PSA levels lower than 0.25 ng/mL, between 0.25 to ≤ 0.69 ng/mL and 0.70 ng/mL, respectively. As a result of the PSMA PET-CT, therapeutic management changed in 38/52 patients (73.1%). Patients had undetectable serum PSA levels after treatment guided by 68Ga-PSMA-11 PET-CT results in 10/52 (19.2%) cases and with a PSA decrease of over 60% in 18/52 (34.6%) patients. CONCLUSION: Whilst our patient population presented a very low PSA level, preliminary results of the 68Ga-PSMA PET-CT study showed recurrence localization in more than half of the patients and this had a major clinical impact, as it resulted in treatment change in more than half of the patients and a significant decrease in PSA levels in a third of patients.

68Ga-PSMA-11 PET-CT study in prostate cancer patients with biochemical recurrence and non-contributive 18F-Choline PET-CT: Impact on therapeutic decision-making and biomarker changes.

BACKGROUND: In this retrospective study, we investigated the impact of 68 Ga-PSMA-11 PET-CT (PSMA PET-CT) upon the treatment plan and therapeutic response obtained for Prostate Cancer (PCa) patients presenting an occult biochemical recurrence. METHODS: Forty-two patients with previously negative or doubtful 18F-Choline (FCH) were enrolled. PET images were recorded 1 h after injection of tracer. Only a few months after treatment ended, a PSA assay was requested to evaluate the therapeutic efficacy of the treatment based on PSMA results. RESULTS: PSMA-positive lesions were detected in 34/42 (80.9%) patients. Detection rates were 85.7% and 89.3% for serum PSA levels lower than 2 ng/mL, and >2 ng/mL, respectively. One hundred seventy-three lesions were detected: 132/173 in lymph nodes (76.3%), 22/173 as metastatic sites (bone or lung) (12.7%), and 19/173 in the prostate bed (10.9%). As a result of the PSMA PET-CT, therapeutic management changed in 31/42 patients (73.8%). With a follow-up of 4.9 ± 2.27 months, 32/42 (76.2%) PSA assays after treatment guided by PSMA PET-CT were collected. For 37.5% (12/32) of patients, the serum PSA level was lower than 0.2 ng/mL and a PSA decrease of over 50% in 8 (25.0%) other patients were obtained. CONCLUSION: Performing a PSMA PET-CT when FCH PET-CT was doubtful or negative allows the recurrence localization in more 80% of patients and this had a major clinical impact, as it resulted in treatment change in more than 70% of patients as well as a significant decrease in PSA levels in more than 60% of them.

Dosimetry results suggest feasibility of radioimmunotherapy using anti-CD138 (B-B4) antibody in multiple myeloma patients.

Syndecan-1 (CD138), a heparan sulfate proteoglycan, is constantly expressed on tumor cells in multiple myeloma (MM). This surface antigen is an attractive candidate for targeted therapy, especially radioimmunotherapy (RAIT). We report preliminary biodistribution and dosimetry results obtained in refractory MM patients in a phase I/II RAIT study using iodine-131-labeled anti-CD138 (B-B4) monoclonal antibody (mAb). Four patients with progressive disease were enrolled after three lines of therapy. They received 370 MBq (20 mg/m(2)) of (131)I-B-B4 for the dosimetry study. Each patient underwent a whole body (WB) CT and four WB emission scans at days D0, D1, and D3-4. Images were corrected for attenuation and scatter to assess doses absorbed by organs and bone marrow (BM). Blood and urine samples were additionally collected. Dosimetry was conducted using the MIRD method. Images obtained 1 h after (131)I-B-B4 injection showed high BM and liver uptake without kidney uptake. The BM uptake confirmed BM involvement as detected by pre-inclusion FDG PET/CT. Absorbed doses were calculated at 2.03 ± 0.3 mGy/MBq for the liver, 1.10 ± 0.9 mGy/MBq for the kidneys, and 0.52 ± 0.20 mGy/MBq for the BM. Grade III thrombocytopenia was documented in two cases (highest BM-absorbed doses), and no grade IV hematological toxicity was observed. Therefore, autologous stem cells were not infused. One patient out of four experienced partial response, with 60% reduction of M-spike on serum electrophoresis, and total relief of pain, lasting for 1 year. This patient was able to go back to work. In this proof of concept study based on dosimetry, we show that MM RAIT is feasible using the anti-CD138 antibody. It would be of great interest to perform a RAIT phase I/II trial with a humanized anti-CD138 mAb with increased doses and systematic autologous stem cell infusions to overcome hematological toxicity and achieve efficacy.