Peptide Receptor Radionuclide Therapy (PRRT) delivers targeted radiation to Somatostatin Receptor (SSR) expressing Neuroendocrine Neoplasms (NEN). We sought to assess the predictive and prognostic implications of tumour dosimetry with respect to response by 68 Ga DOTATATE (GaTate) PET/CT molecular imaging tumour volume of SSR (MITVSSR) change and RECIST 1.1, and overall survival (OS). Patients with gastro-entero-pancreatic (GEP) NEN who received LuTate followed by quantitative SPECT/CT (Q-SPECT/CT) the next day (Jul 2010 to Jan 2019) were retrospectively reviewed. Single time-point (STP) lesional dosimetry was performed for each cycle using population-based pharmacokinetic modelling. MITVSSR and RECIST 1.1 were measured at 3-months post PRRT. Median of 4 PRRT cycles were administered to 90 patients (range 2–5 cycles; mean 27.4 GBq cumulative activity; mean 7.6 GBq per cycle). 68

ImmunoPET is a multicentre, single arm, phase 1 study that investigates the use of 89Zr-durvalumab PET/CT to interrogate the expression of PD-L1 in Stage III NSCLC undergoing concurrent chemo-radiotherapy. We present here the study details and initial results from our first patient.

BackgroundLutetium-177 [177Lu]-PSMA-617 is a targeted radioligand that binds to prostate-specific membrane antigen (PSMA) and delivers radiation to metastatic prostate cancer. The presence of PSMA-negative/FDG-positive metastases can preclude patients from being eligible for this treatment. Biology-guided radiotherapy (BgRT) is a treatment modality that utilises tumour PET emissions to guide external beam radiotherapy. The feasibility of combining BgRT and Lutetium-177 [177Lu]-PSMA-617 for patients with PSMA-negative/FDG-positive metastatic prostate cancer was explored.Materials and methodsAll patients excluded from the LuPSMA clinical trial (ID: ANZCTR12615000912583) due to PSMA/FDG discordance were retrospectively reviewed. A hypothetical workflow where PSMA-negative/FDG-positive metastases would be treated with BgRT whilst PSMA-positive metastases would be treated with Lutetium-177 [177Lu]-PSMA-617 was considered. Gross tumour volume (GTV) of PSMA-negative/FDG-positive tumours were delineated on the CT component of the FDG PET/CT scan. Tumours were deemed suitable for BgRT if (1) normalised SUV (nSUV), defined as the ratio of maximum SUV (SUVmax) inside the GTV to mean SUV inside a 5 mm/10 mm/20 mm margin expansion of the GTV, was larger than a pre-specified nSUV threshold and (2) there was no PET avidity inside the margin expansion.ResultsIn 75 patients screened for Lutetium-177 [177Lu]-PSMA-617 treatment, 6 patients were excluded due to PSMA/FDG discordance and 89 PSMA-negative/FDG-positive targets were identified. GTV volumes ranged from 0.3 cm3 to 186 cm3 (median GTV volume = 4.3 cm3, IQR = 2.2 cm3 – 7.4 cm3). SUVmax inside GTVs ranged between 3 and 12 (median SUVmax = 4.8, IQR = 3.9 – 6.2). With nSUV ≥ 3, 67%/54%/39% of all GTVs were suitable for BgRT within 5 mm/10 mm/20 mm from the tumour. Bone and lung metastases were the best candidates for BgRT (40%/27% of all tumours suitable for BgRT with nSUV ≥ 3 within 5 mm from the GTV were bone/lung GTVs).ConclusionsCombined BgRT/Lutetium-177 [177Lu]-PSMA-617 therapy is feasible for patients with PSMA/FDG discordant metastases.

Background:Biology-guided radiotherapy (BgRT) is a novel treatment where the detection of positron emission originating from a volume called the biological tracking zone (BTZ) initiates dose delivery. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is a novel imaging technique that may improve patient selection for metastasis-directed therapy in renal cell carcinoma (RCC). This study aims to determine the feasibility of BgRT treatment for RCC. Material and methods:All consecutive patients that underwent PSMA PET/CT scan for RCC staging at our institution between 2014 and 2020 were retrospectively considered for inclusion. GTVs were contoured on the CT component of the PET/CT scan. The tumor-to-background ratio was quantified from the normalized standardized uptake value (nSUV), defined as the ratio between SUVmax inside the GTV and SUVmean inside the margin expansion. Tumors were classified suitable for BgRT if (1) nSUV was greater or equal to an nSUV threshold and (2) if the BTZ was free of any PET-avid region other than the tumor. Results:Out of this cohort of 83 patients, 47 had metastatic RCC and were included in this study. In total, 136 tumors were delineated, 1 to 22 tumors per patient, mostly in lung (40%). Using a margin expansion of 5 mm/10 mm/20 mm and nSUV threshold = 3, 66%/63%/41% of tumors were suitable for BgRT treatment. Uptake originating from another tumor, the kidney, or the liver was typically inside the BTZ in tumors judged unsuitable for BgRT. Conclusions:More than 60% of tumors were found to be suitable for BgRT in this cohort of patients with RCC. However, the proximity of PET-avid organs such as the liver or the kidney may affect BgRT delivery.

An nSUV greater than 3 was achieved in more than 95% of all GTVs for all shell thicknesses investigated in this study, which suggests that PSMA-guided BgRT is a feasible modality for sequential boost directed at the dPSMA-avid subvolume in the prostate region. If bladder proximity impacts geometric specificity of BgRT delivery or if greater tumor-to-background contrast is desired, additional refinements may be required. These may include modifications to the BgRT algorithm that enable masking of the bladder. Clinical trial number ACTRN12617000005358.

Biology-guided radiation therapy (BgRT) guides radiation therapy in real time based on positron emissions detected during treatment delivery. Protein specific membrane antigen (PSMA) is a positron emission tomography (PET) tracer with superior sensitivity and specificity for prostate cancer detection compared with conventional imaging. This study aims to quantify the ratio of standard uptake value (SUV) to background SUV for patients with low volume prostate cancer metastases, in the context of determining suitability of these lesions for BgRT. A single institutional patient subset from the ProPSMA prospective clinical trial underwent Ga-68-PSMA-11 at the time of prostate cancer diagnosis with suspected localized disease. From this cohort of 84 patients, 15 had at least one metastatic site disease diagnosed, 1 to 11 lesions per patient, with a total of 43 metastatic lesions (12 bones/31 viscerals). Metastatic gross tumor volume (GTV) were delineated on PSMA-PET images by using a patient-specific fixed SUV threshold method. In order to determine the suitability of various BgRT tracking zones, 3D shells of thickness 5 mm, 10 mm and 20 mm were constructed around the GTV to represent adjacent non-tumor background. Normalized SUV (nSUV) was calculated as the ratio of SUVmax in the GTV to SUVmean of adjacent shell. Sensitivity of nSUV to shell thickness variation was reported as the difference between nSUV values obtained for each thickness. GTV SUVmax ranged from 2.9 to 48.0 (median, 12.0; IQR, 5.1 to 19.5). nSUV ranged from 2.4 to 42.6 for 5 mm shell, 2.7 to 47.5 for 10 mm shell and 2.6 to 36.4 for 20 mm shell. Bone metastases had increased SUVmax compared with visceral metastases (SUVmax min/median/max 2.9/15.0/48.0 for bone compared with 2.9/11.0/40.0 for visceral). Furthermore, 90% of lesions had nSUV greater than 2.9 for a shell thickness of 5 mm, 3.1 for a shell thickness of 10 mm, and 3.2 for a shell thickness of 20 mm. Moreover, 100%/93%/84% of lesions would be suitable for BgRT by using nSUV cut-off of 2/3/4 and a shell thickness of 10 mm. nSUV decreased with increasing shell thickness for 17 lesions, indicating high signal in adjacent non-tumor tissue due to the proximity of bladder (5), bowel (4), other lesion (4), vessel (3) and liver (1). This study demonstrates that it is feasible to identify metabolically defined radiotherapy targets in the setting of BgRT. High lesion to background signal was observed for metastases visible on Ga-PSMA-EPT-11, however a subset of metastases had adjacent non-tumor uptake which may require exclusion from emission tracking during BgRT. Trial ID ACTRN12617000005358.