BIOGUIDE-X: A First-in-Human Study of the Performance of Positron Emission Tomography-Guided Radiation Therapy.

PURPOSE: Positron emission tomography (PET)-guided radiation therapy is a novel tracked dose delivery modality that uses real-time PET to guide radiation therapy beamlets. The BIOGUIDE-X study was performed with sequential cohorts of participants to (1) identify the fluorodeoxyglucose (FDG) dose for PET-guided therapy and (2) confirm that the emulated dose distribution was consistent with a physician-approved radiation therapy plan. METHODS AND MATERIALS: This prospective study included participants with at least 1 FDG-avid targetable primary or metastatic tumor (2-5 cm) in the lung or bone. For cohort I, a modified 3 + 3 design was used to determine the FDG dose that would result in adequate signal for PET-guided therapy. For cohort II, PET imaging data were collected on the X1 system before the first and last fractions among patients undergoing conventional stereotactic body radiation therapy. PET-guided therapy dose distributions were modeled on the patient's computed tomography anatomy using the collected PET data at each fraction as input to an "emulated delivery" and compared with the physician-approved plan. RESULTS: Cohort I demonstrated adequate FDG activity in 6 of 6 evaluable participants (100.0%) with the first injected dose level of 15 mCi FDG. In cohort II, 4 patients with lung tumors and 5 with bone tumors were enrolled, and evaluable emulated delivery data points were collected for 17 treatment fractions. Sixteen of the 17 emulated deliveries resulted in dose distributions that were accurate with respect to the approved PET-guided therapy plan. The 17th data point was just below the 95% threshold for accuracy (dose-volume histogram score = 94.6%). All emulated fluences were physically deliverable. No toxicities were attributed to multiple FDG administrations. CONCLUSIONS: PET-guided therapy is a novel radiation therapy modality in which a radiolabeled tumor can act as its own fiducial for radiation therapy targeting. Emulated therapy dose distributions calculated from continuously acquired real-time PET data were accurate and machine-deliverable in tumors that were 2 to 5 cm in size with adequate FDG signal characteristics.

Comparative evaluation of treatment plan quality for a prototype biology-guided radiotherapy system in the treatment of nasopharyngeal carcinoma.

We aimed to compare prototype treatment plans for a new biology-guided radiotherapy (BgRT) machine in its intensity-modulated radiation therapy (IMRT) mode with those using existing IMRT delivery techniques in treatment of nasopharyngeal carcinoma (NPC). We retrospectively selected ten previous NPC patients treated in 33 fractions according to the NRG-HN001 treatment protocol. Three treatment plans were generated for each patient: a helical tomotherapy (HT) plan with a 2.5-cm jaw, a volumetric modulated arc therapy (VMAT) plan using 2 to 4 6-MV arc fields, and a prototype IMRT plan for a new BgRT system which uses a 6-MV photon beam on a ring gantry that rotates at 60 rotations per minute with a couch that moves in small incremental steps. Treatment plans were compared using dosimetric parameters to planning target volumes (PTVs) and organs at risk (OARs) as specified by the NRG-HN001 protocol. Plans for the three modalities had comparable dose coverage, mean dose, and dose heterogeneity to the primary PTV, while the prototype IMRT plans had greater dose heterogeneity to the non-primary PTVs, with the average homogeneity index ranging from 1.28 to 1.50 in the prototype plans. Six of all the 7 OAR mean dose parameters were lower with statistical significance in the prototype plans compared to the HT and VMAT plans with the other mean dose parameter being comparable, and all the 18 OAR maximum dose parameters were comparable or lower with statistical significance in the prototype plans. The average left and right parotid mean doses in the prototype plans were 10.5 Gy and 10.4 Gy lower than those in the HT plans, respectively, and were 5.1 Gy and 5.2 Gy lower than those in the VMAT plans, respectively. Compared to that with the HT and VMAT plans, the treatment time was longer with statistical significance with the prototype IMRT plans. Based on dosimetric comparison of ten NPC cases, the prototype IMRT plans achieved comparable or better critical organ sparing compared to the HT and VMAT plans for definitive NPC radiotherapy. However, there was higher dose heterogeneity to non-primary targets and longer estimated treatment time with the prototype plans.

Online Prostate-Specific Membrane Antigen and Positron Emission Tomography-Guided Radiation Therapy for Oligometastatic Prostate Cancer.

PURPOSE: Stereotactic ablative radiation therapy (SABR) for oligometastatic prostate cancer (OMPC) may improve clinical outcomes, but current challenges in intrafraction tracking of multiple small targets limits treatment accuracy. A biology-guided radiation therapy (BgRT) delivery system incorporating positron emission tomography (PET) detectors is being developed to use radiotracer uptake as a biologic fiducial for intrafraction tumor tracking to improve geometric accuracy. This study simulates prostate-specific membrane antigen (PSMA)-directed BgRT using a cohort from our phase II randomized trial of SABR in men with recurrent hormone sensitive OMPC and compares dose distributions to clinical SABR (CSABR). METHODS AND MATERIALS: A research treatment planning system (RTPS) was used to replan 15 patients imaged with PSMA-targeted 18F-DCFPyL PET/computed tomography and previously treated with CSABR using conventional linear accelerators (linacs). The RTPS models a prototype ring-mounted linac incorporating PET and kilo-voltage computed tomography imaging subsystems and can be used to optimize BgRT plans, as well as research SABR (RSABR) plans, which use the prototype linac without radiotracer guidance. CSABR, RSABR, and BgRT plans were compared in terms of maximum planning target volume (PTV) dose (Dmax), mean dose to proximal organs at risk (DOAR), conformity index, as well as voxel-wise correlation of dose with PET specific uptake values to investigate possible dose-painting effects. RESULTS: RSABR and BgRT plans resulted in mean ± standard deviation increases in Dmax of 4 ± 11% (P = .21) and 18 ± 15% (P < .001) and reductions in DOAR of -20 ± 19% (P <.001) and -10 ± 19% (P = .02) compared with CSABR. Similar target coverage was maintained with conformity indices of 0.81 ± 0.04 (P < .001) and 0.72 ± 0.08 (P = .44) for RSABR and BgRT compared with 0.74 ± 0.08 for CSABR. Dose and log (specific uptake values) had Pearson correlation coefficients of 0.10 (CSABR), 0.16 (RSABR), and 0.31 (BgRT). CONCLUSIONS: BgRT plans provided similar PTV coverage and conformity compared with CSABR while incorporating underlying PET activity. These results demonstrate feasibility of BgRT optimization enabling online PSMA-targeted, PET-based tracked dose delivery for OMPC.

Feasibility and preliminary results of SPECT/CT arthrography of the wrist in comparison with MR arthrography in patients with suspected ulnocarpal impaction.

PURPOSE: To evaluate the feasibility and performance of SPECT/CT arthrography of the wrist in comparison with MR arthrography in patients with suspected ulnocarpal impaction. METHODS: This prospective study included 28 wrists of 27 patients evaluated with SPECT/CT arthrography and MR arthrography. Iodine contrast medium and gadolinium were injected into the distal radioulnar and midcarpal joints. Late-phase SPECT/CT was performed 3.5 h after intravenous injection of approximately 650 MBq (99m)Tc-DPD. MR and SPECT/CT images were separately reviewed in relation to bone marrow oedema, radionuclide uptake, and tears in the scapholunate (SL) and lunotriquetral (LT) ligaments and triangular fibrocartilage complex (TFCC), and an overall diagnosis of ulnar impaction. MR, CT and SPECT/CT imaging findings were compared with each other, with the surgical findings in 12 patients and with clinical follow-up. RESULTS: The quality of MR arthrography and SPECT/CT arthrography images was fully diagnostic in 23 of 28 wrists (82%) and 25 of 28 wrists (89%), respectively. SPECT/CT arthrography was not diagnostic for ligament lesions due to insufficient intraarticular contrast in one wrist. MR and SPECT/CT images showed concordant findings regarding TFCC lesions in 22 of 27 wrists (81%), SL ligament in 22 of 27 wrists (81%) and LT ligament in 23 of 27 wrists (85%). Bone marrow oedema on MR images and scintigraphic uptake were concordant in 21 of 28 wrists (75%). MR images showed partial TFCC defects in four patients with normal SPECT/CT images. MR images showed bone marrow oedema in 4 of 28 wrists (14%) without scintigraphic uptake, and scintigraphic uptake was present without MR bone marrow oedema in three wrists (11%). Regarding diagnosis of ulnar impaction the concordance rate between CT and SPECT/CT was 100% and reached 96% (27 of 28) between MR and SPECT/CT arthrography. The sensitivity and specificity of MR, CT and SPECT/CT arthrography were 93%, 100% and 100%, and 93%, 93% and 93%, respectively. CONCLUSION: SPECT/CT arthrography of the wrist is feasible. Regarding diagnosis of ulnar impaction we found a high concordance with MR arthrography. SPECT/CT arthrography of the wrist is an alternative to MR arthrography in patients with contraindications to MR imaging.

Clinical utility of SPECT-(low-dose)CT versus SPECT alone in patients presenting for bone scintigraphy.

PURPOSE: This prospective study evaluated the contribution of single-photon emission computed tomography (SPECT)-(low-dose)CT (SPECT-ldCT) over SPECT alone in all-comers referred for bone scintigraphy for any indication. METHODS: In this prospective study, imaging was performed on 100 consecutive patients who presented for bone scintigraphy using a combined SPECT-ldCT single-gantry system (Brightview XCT, Philips Medical Systems Inc., Cleveland, OH). SPECT images were reconstructed with (AC) and without (NAC) attenuation and scatter correction. SPECT (NAC), SPECT-ldCT (NAC), and SPECT-ldCT (AC) were reviewed independently and in a blinded manner. Reader interpretation of images was compared with the final clinical diagnosis. RESULTS: Subjects were referred for oncologic (28%) and nononcologic (72%) indications. Attenuation correction significantly improved perceived image quality (P = 0.012), but did not significantly alter diagnostic confidence (P = 0.96). Availability of ldCT data during interpretation of the SPECT images yielded a significant increase in the level of diagnostic confidence (P < 0.001). When the ldCT data were available, 18 of 200 bone SPECT reads recommended additional diagnostic CT imaging, compared with 70 when ldCT data were unavailable at the time of reading (P < 0.001). The sensitivity, specificity, and accuracy of SPECT-ldCT (with or without attenuation and scatter correction) in the diagnosis of osseous processes were 90.9%, 85.9%, and 87.0%, respectively, and these values did not differ significantly from those obtained with SPECT alone. CONCLUSIONS: Bone SPECT-ldCT provides interpreting physicians a significantly greater level of diagnostic confidence and reduces additional diagnostic imaging studies, but the overall diagnostic accuracy of SPECT-ldCT was not affected when compared with SPECT alone, suggesting that SPECT-ldCT should be used on a patient-by-patient basis.

Dual-modality imaging of function and physiology.

Dual-modality imaging is a technique in which computed tomography (CT) or magnetic resonance imaging is combined with positron emission tomography or single-photon emission CT to acquire structural and functional images with an integated system. The data are acquired in a single procedure; the patient remains on the scanner table while undergoing both x-ray and radionuclide studies to facilitate correlation between the structural and functional images. The resulting data can aid in localization, enabling more specific diagnosis than can be obtained with a conventional imaging study. In addition, the anatomic information can be used to compensate the correlated radionuclide data for physical perturbations such as photon attenuation, scatter radiation, and partial volume errors. Thus, dual-modality imaging provides a priori information that can improve both the visual quality and the quantitative accuracy of the radionuclide images. Dual-modality imaging systems are also being developed for biologic research involving small animals. Small-animal dual-modality systems offer advantages for measurements that currently are performed invasively with autoradiography and tissue sampling. By acquiring data noninvasively, dual-modality imaging permits serial studies in a single animal, enables measurements to be performed with fewer animals, and improves the statistical quality of the data.